@article {49773, title = {Capturing the most wanted taxa through cross-sample correlations}, journal = {The ISME Journal}, year = {2016}, month = {Apr-03-2016}, issn = {1751-7362}, doi = {10.1038/ismej.2016.35}, url = {http://www.nature.com/doifinder/10.1038/ismej.2016.35}, author = {Almeida, Mathieu and Pop, Mihai and Le Chatelier, Emmanuelle and Prifti, Edi and Pons, Nicolas and Ghozlane, Amine and Ehrlich, S Dusko} } @article {49668, title = {The fruRBA operon is necessary for Group A Streptococcal growth in fructose and for resistance to neutrophil killing during growth in whole human blood.}, journal = {Infect Immun}, year = {2016}, month = {2016 Jan 19}, abstract = {

Bacterial pathogens rely on the availability of nutrients for survival in the host environment. The phosphoenolpyruvate-phosphotransferase system (PTS) is a global regulatory network connecting sugar uptake with signal transduction. Since the fructose PTS has been shown to impact virulence in several Streptococci, including the human pathogen S. pyogenes (the group A Streptococcus, GAS), we characterized its role in carbon metabolism and pathogenesis in the M1T1 strain 5448. Growth in fructose as a sole carbon source resulted in 103 genes affected transcriptionally, where the fru locus (fruRBA) was the most induced. RT-PCR showed that fruRBA formed an operon, which was repressed by FruR in the absence of fructose, in addition to being under carbon catabolic repression. Growth assays and carbon utilization profiles revealed that although the entire fru operon was required for growth in fructose, FruA was the main transporter for fructose and was also involved in the utilization of three additional PTS sugars: cellobiose, mannitol, and N-acetyl-D-galactosamine. Inactivation of sloR, a fruA homolog that was also up regulated in presence of fructose, failed to reveal a role as a secondary fructose transporter. Whereas the ability of both ΔfruR and ΔfruB mutants to survive in the presence of whole human blood or neutrophils was impaired, the phenotype was not reproduced in murine whole blood, nor were those mutants attenuated in a mouse intraperitoneal infection. Since the ΔfruA mutant exhibited no phenotype in the human or mouse assays, we propose that FruR and FruB are important for GAS survival in a human-specific environment.

}, issn = {1098-5522}, doi = {10.1128/IAI.01296-15}, author = {Valdes, Kayla M and Sundar, Ganesh S and Vega, Luis A and Belew, Ashton T and Islam, Emrul and Binet, Rachel and El-Sayed, Najib M and Le Breton, Yoann and McIver, Kevin S} } @article {49795, title = {The fruRBA Operon Is Necessary for Group A Streptococcal Growth in Fructose and for Resistance to Neutrophil Killing during Growth in Whole Human Blood}, journal = {Infection and Immunity}, volume = {84}, year = {2016}, month = {Dec-04-2017}, pages = {1016 - 1031}, issn = {0019-9567}, doi = {10.1128/IAI.01296-15}, url = {http://iai.asm.org/lookup/doi/10.1128/IAI.01296-15}, author = {Valdes, Kayla M. and Sundar, Ganesh S. and Vega, Luis A. and Belew, Ashton T. and Islam, Emrul and Binet, Rachel and El-Sayed, Najib M. and Le Breton, Yoann and McIver, Kevin S.}, editor = {Camilli, A.} } @article {49791, title = {Individual-specific changes in the human gut microbiota after challenge with enterotoxigenic Escherichia coli and subsequent ciprofloxacin treatment}, journal = {BMC Genomics}, volume = {17183412111831230710512122489914142853341501081566039108377115651846133171373920352123327102188151723}, year = {2016}, month = {Jan-12-2016}, doi = {10.1186/s12864-016-2777-0}, url = {http://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-016-2777-0http://link.springer.com/content/pdf/10.1186/s12864-016-2777-0}, author = {Pop, Mihai and Paulson, Joseph N. and Chakraborty, Subhra and Astrovskaya, Irina and Lindsay, Brianna R. and Li, Shan and Bravo, {\'e}ctor Corrada and Harro, Clayton and Parkhill, Julian and Walker, Alan W. and Walker, Richard I. and Sack, David A. and Stine, O. Colin} } @article {49799, title = {System-wide Clinical Proteomics of Breast Cancer Reveals Global Remodeling of Tissue Homeostasis.}, journal = {Cell Syst}, volume = {2}, year = {2016}, month = {2016 Mar 23}, pages = {172-84}, abstract = {

The genomic and transcriptomic landscapes of breast cancer have been extensively studied, but the proteomes of breast tumors are far less characterized. Here, we use high-resolution, high-accuracy mass spectrometry to perform a deep analysis of luminal-type breast cancer progression using clinical breast samples from primary tumors, matched lymph node metastases, and healthy breast epithelia. We used a super-SILAC mix to quantify over 10,000 proteins with high accuracy, enabling us to identify key proteins and pathways associated with tumorigenesis and metastatic spread. We found high expression levels of proteins associated with protein synthesis and degradation in cancer tissues, accompanied by metabolic alterations that may facilitate energy production in cancer cells within their natural environment. In addition, we found proteomic differences between breast cancer stages and minor differences between primary tumors and their matched lymph node metastases. These results highlight the potential of proteomic technology in the elucidation of clinically relevant cancer signatures.

}, issn = {2405-4712}, doi = {10.1016/j.cels.2016.02.001}, author = {Pozniak, Yair and Balint-Lahat, Nora and Rudolph, Jan Daniel and Lindskog, Cecilia and Katzir, Rotem and Avivi, Camilla and Pont{\'e}n, Fredrik and Ruppin, Eytan and Barshack, Iris and Geiger, Tamar} } @article {49817, title = {Therapeutic relevance of the protein phosphatase 2A in cancer}, journal = {Oncotarget.com}, year = {2016}, month = {Jul-09-2017}, doi = {10.18632/oncotarget.11399}, url = {https://www.oncotarget.com/article/11399}, author = {Cunningham, Chelsea E. and Li, Shuangshuang and Vizeacoumar, Frederick S. and Bhanumathy, Kalpana Kalyanasundaram and Lee, Joo Sang and Parameswaran, Sreejit and Furber, Levi and Abuhussein, Omar and Paul, James M. and McDonald, Megan and Templeton, Shaina D. and Shukla, Hersh and El Zawily, Amr M. and Boyd, Frederick and Alli, Nezeka and Mousseau, Darrell D. and Geyer, Ron and Bonham, Keith and Anderson, Deborah H. and Yan, Jiong and Yu-Lee, Li-Yuan and Weaver, Beth A. and Uppalapati, Maruti and Ruppin, Eytan and Sablina, Anna and Freywald, Andrew and Vizeacoumar, Franco J.} } @article {49794, title = {Transcriptome Remodeling in Trypanosoma cruzi and Human Cells during Intracellular Infection.}, journal = {PLoS Pathog}, volume = {12}, year = {2016}, month = {2016 Apr}, pages = {e1005511}, abstract = {

Intracellular colonization and persistent infection by the kinetoplastid protozoan parasite, Trypanosoma cruzi, underlie the pathogenesis of human Chagas disease. To obtain global insights into the T. cruzi infective process, transcriptome dynamics were simultaneously captured in the parasite and host cells in an infection time course of human fibroblasts. Extensive remodeling of the T. cruzi transcriptome was observed during the early establishment of intracellular infection, coincident with a major developmental transition in the parasite. Contrasting this early response, few additional changes in steady state mRNA levels were detected once mature T. cruzi amastigotes were formed. Our findings suggest that transcriptome remodeling is required to establish a modified template to guide developmental transitions in the parasite, whereas homeostatic functions are regulated independently of transcriptomic changes, similar to that reported in related trypanosomatids. Despite complex mechanisms for regulation of phenotypic expression in T. cruzi, transcriptomic signatures derived from distinct developmental stages mirror known or projected characteristics of T. cruzi biology. Focusing on energy metabolism, we were able to validate predictions forecast in the mRNA expression profiles. We demonstrate measurable differences in the bioenergetic properties of the different mammalian-infective stages of T. cruzi and present additional findings that underscore the importance of mitochondrial electron transport in T. cruzi amastigote growth and survival. Consequences of T. cruzi colonization for the host include dynamic expression of immune response genes and cell cycle regulators with upregulation of host cholesterol and lipid synthesis pathways, which may serve to fuel intracellular T. cruzi growth. Thus, in addition to the biological inferences gained from gene ontology and functional enrichment analysis of differentially expressed genes in parasite and host, our comprehensive, high resolution transcriptomic dataset provides a substantially more detailed interpretation of T. cruzi infection biology and offers a basis for future drug and vaccine discovery efforts.

}, issn = {1553-7374}, doi = {10.1371/journal.ppat.1005511}, author = {Li, Yuan and Shah-Simpson, Sheena and Okrah, Kwame and Belew, A Trey and Choi, Jungmin and Caradonna, Kacey L and Padmanabhan, Prasad and Ndegwa, David M and Temanni, M Ramzi and Corrada Bravo, Hector and El-Sayed, Najib M and Burleigh, Barbara A} } @article {49623, title = {Bayesian integration of genetics and epigenetics detects causal regulatory SNPs underlying expression variability}, journal = {Nature Communications}, volume = {6}, year = {2015}, month = {Dec-10-2015}, pages = {8555}, doi = {10.1038/ncomms9555}, url = {http://www.nature.com/doifinder/10.1038/ncomms9555}, author = {Das, Avinash and Morley, Michael and Moravec, Christine S. and Tang, W. H. W. and Hakonarson, Hakon and Ashley, Euan A. and Brandimarto, Jeffrey and Hu, Ray and Li, Mingyao and Li, Hongzhe and Liu, Yichuan and Qu, Liming and Sanchez, Pablo and Margulies, Kenneth B. and Cappola, Thomas P. and Jensen, Shane and Hannenhalli, Sridhar} } @article {49733, title = {Drugs that reverse disease transcriptomic signatures are more effective in a mouse model of dyslipidemia.}, journal = {Mol Syst Biol}, volume = {11}, year = {2015}, month = {2015 Mar}, pages = {791}, abstract = {

High-throughput omics have proven invaluable in studying human disease, and yet day-to-day clinical practice still relies on physiological, non-omic markers. The metabolic syndrome, for example, is diagnosed and monitored by blood and urine indices such as blood cholesterol levels. Nevertheless, the association between the molecular and the physiological manifestations of the disease, especially in response to treatment, has not been investigated in a systematic manner. To this end, we studied a mouse model of diet-induced dyslipidemia and atherosclerosis that was subject to various drug treatments relevant to the disease in question. Both physiological data and gene expression data (from the liver and white adipose) were analyzed and compared. We find that treatments that restore gene expression patterns to their norm are associated with the successful restoration of physiological markers to their baselines. This holds in a tissue-specific manner{\textemdash}treatments that reverse the transcriptomic signatures of the disease in a particular tissue are associated with positive physiological effects in that tissue. Further, treatments that introduce large non-restorative gene expression alterations are associated with unfavorable physiological outcomes. These results provide a sound basis to in silico methods that rely on omic metrics for drug repurposing and drug discovery by searching for compounds that reverse a disease{\textquoteright}s omic signatures. Moreover, they highlight the need to develop drugs that restore the global cellular state to its healthy norm rather than rectify particular disease phenotypes.

}, issn = {1744-4292}, author = {Wagner, Allon and Cohen, Noa and Kelder, Thomas and Amit, Uri and Liebman, Elad and Steinberg, David M and Radonjic, Marijana and Ruppin, Eytan} } @article {49578, title = {The effects of telomere shortening on cancer cells: a network model of proteomic and microRNA analysis.}, volume = {105}, year = {2015}, month = {2015 Jan}, pages = {5-16}, abstract = {

Previously, we have shown that shortening of telomeres by telomerase inhibition sensitized cancer cells to cisplatinum, slowed their migration, increased DNA damage and impaired DNA repair. The mechanism behind these effects is not fully characterized. Its clarification could facilitate novel therapeutics development and may obviate the time consuming process of telomere shortening achieved by telomerase inhibition. Here we aimed to decipher the microRNA and proteomic profiling of cancer cells with shortened telomeres and identify the key mediators in telomere shortening-induced damage to those cells. Of 870 identified proteins, 98 were differentially expressed in shortened-telomere cells. 47 microRNAs were differentially expressed in these cells; some are implicated in growth arrest or act as oncogene repressors. The obtained data was used for a network construction, which provided us with nodal candidates that may mediate the shortened-telomere dependent features. These proteins{\textquoteright} expression was experimentally validated, supporting their potential central role in this system.

}, keywords = {Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, HUMANS, MicroRNAs, Neoplasms, Oligonucleotides, Proteome, proteomics, Telomere Shortening, Tumor Cells, Cultured}, issn = {1089-8646}, doi = {10.1016/j.ygeno.2014.10.013}, author = {Uziel, O and Yosef, N and Sharan, R and Ruppin, E and Kupiec, M and Kushnir, M and Beery, E and Cohen-Diker, T and Nordenberg, J and Lahav, M} } @article {49537, title = {Essential Genes in the Core Genome of the Human Pathogen Streptococcus pyogenes.}, journal = {Sci Rep}, volume = {5}, year = {2015}, month = {2015}, pages = {9838}, abstract = {

Streptococcus pyogenes (Group A Streptococcus, GAS) remains a major public health burden worldwide, infecting over 750 million people leading to over 500,000 deaths annually. GAS pathogenesis is complex, involving genetically distinct GAS strains and multiple infection sites. To overcome fastidious genetic manipulations and accelerate pathogenesis investigations in GAS, we developed a mariner-based system (Krmit) for en masse monitoring of complex mutant pools by transposon sequencing (Tn-seq). Highly saturated transposant libraries (Krmit insertions in ca. every 25 nucleotides) were generated in two distinct GAS clinical isolates, a serotype M1T1 invasive strain 5448 and a nephritogenic serotype M49 strain NZ131, and analyzed using a Bayesian statistical model to predict GAS essential genes, identifying sets of 227 and 241 of those genes in 5448 and NZ131, respectively. A large proportion of GAS essential genes corresponded to key cellular processes and metabolic pathways, and 177 were found conserved within the GAS core genome established from 20 available GAS genomes. Selected essential genes were validated using conditional-expression mutants. Finally, comparison to previous essentiality analyses in S. sanguinis and S. pneumoniae revealed significant overlaps, providing valuable insights for the development of new antimicrobials to treat infections by GAS and other pathogenic streptococci.

}, issn = {2045-2322}, doi = {10.1038/srep09838}, author = {Le Breton, Yoann and Belew, Ashton T and Valdes, Kayla M and Islam, Emrul and Curry, Patrick and Tettelin, Herv{\'e} and Shirtliff, Mark E and El-Sayed, Najib M and McIver, Kevin S} } @article {49579, title = {Fumarate induces redox-dependent senescence by modifying glutathione metabolism.}, volume = {6}, year = {2015}, month = {2015}, pages = {6001}, abstract = {

Mutations in the tricarboxylic acid (TCA) cycle enzyme fumarate hydratase (FH) are associated with a highly malignant form of renal cancer. We combined analytical chemistry and metabolic computational modelling to investigate the metabolic implications of FH loss in immortalized and primary mouse kidney cells. Here, we show that the accumulation of fumarate caused by the inactivation of FH leads to oxidative stress that is mediated by the formation of succinicGSH, a covalent adduct between fumarate and glutathione. Chronic succination of GSH, caused by the loss of FH, or by exogenous fumarate, leads to persistent oxidative stress and cellular senescence in vitro and in vivo. Importantly, the ablation of p21, a key mediator of senescence, in Fh1-deficient mice resulted in the transformation of benign renal cysts into a hyperplastic lesion, suggesting that fumarate-induced senescence needs to be bypassed for the initiation of renal cancers.

}, issn = {2041-1723}, doi = {10.1038/ncomms7001}, author = {Zheng, Liang and Cardaci, Simone and Jerby, Livnat and MacKenzie, Elaine D and Sciacovelli, Marco and Johnson, T Isaac and Gaude, Edoardo and King, Ayala and Leach, Joshua D G and Edrada-Ebel, RuAngelie and Hedley, Ann and Morrice, Nicholas A and Kalna, Gabriela and Blyth, Karen and Ruppin, Eytan and Frezza, Christian and Gottlieb, Eyal} } @article {49659, title = {Glutamine synthetase activity fuels nucleotide biosynthesis and supports growth of glutamine-restricted glioblastoma}, journal = {Nature Cell Biology}, volume = {17}, year = {2015}, month = {Nov-11-2016}, pages = {1556 - 1568}, issn = {1465-7392}, doi = {10.1038/ncb3272}, url = {http://www.nature.com/doifinder/10.1038/ncb3272}, author = {Tardito, Saverio and Oudin, {\"\i}s and Ahmed, Shafiq U. and Fack, Fred and Keunen, Olivier and Zheng, Liang and Miletic, Hrvoje and Sakariassen, {\O}ystein and Weinstock, Adam and Wagner, Allon and Lindsay, Susan L. and Hock, Andreas K. and Barnett, Susan C. and Ruppin, Eytan and {\o}rkve, Svein Harald and Lund-Johansen, Morten and Chalmers, Anthony J. and Bjerkvig, Rolf and Niclou, Simone P. and Gottlieb, Eyal} } @article {49723, title = {Harnessing the landscape of microbial culture media to predict new organism-media pairings.}, journal = {Nat Commun}, volume = {6}, year = {2015}, month = {2015}, pages = {8493}, abstract = {

Culturing microorganisms is a critical step in understanding and utilizing microbial life. Here we map the landscape of existing culture media by extracting natural-language media recipes into a Known Media Database (KOMODO), which includes >18,000 strain-media combinations, >3300 media variants and compound concentrations (the entire collection of the Leibniz Institute DSMZ repository). Using KOMODO, we show that although media are usually tuned for individual strains using biologically common salts, trace metals and vitamins/cofactors are the most differentiating components between defined media of strains within a genus. We leverage KOMODO to predict new organism-media pairings using a transitivity property (74\% growth in new in vitro experiments) and a phylogeny-based collaborative filtering tool (83\% growth in new in vitro experiments and stronger growth on predicted well-scored versus poorly scored media). These resources are integrated into a web-based platform that predicts media given an organism{\textquoteright}s 16S rDNA sequence, facilitating future cultivation efforts.

}, issn = {2041-1723}, doi = {10.1038/ncomms9493}, author = {Oberhardt, Matthew A and Zarecki, Raphy and Gronow, Sabine and Lang, Elke and Klenk, Hans-Peter and Gophna, Uri and Ruppin, Eytan} } @article {49512, title = {Independent Emergence of Artemisinin Resistance Mutations Among Plasmodium falciparum in Southeast Asia}, journal = {Journal of Infectious Diseases}, volume = {211}, year = {2015}, month = {03/2015}, pages = {670 - 679}, issn = {1537-6613}, doi = {10.1093/infdis/jiu491}, author = {Takala-Harrison, S. and Jacob, C. G. and Arze, C. and Michael P. Cummings and Silva, J. C. and Dondorp, A. M. and Fukuda, M. M. and Hien, T. T. and Mayxay, M. and Noedl, H. and Nosten, F. and Kyaw, M. P. and Nhien, N. T. T. and Imwong, M. and Bethell, D. and Se, Y. and Lon, C. and Tyner, S. D. and Saunders, D. L. and Ariey, F. and Mercereau-Puijalon, O. and Menard, D. and Newton, P. N. and Khanthavong, M. and Hongvanthong, B. and Starzengruber, P. and Fuehrer, H.-P. and Swoboda, P. and Khan, W. A. and Phyo, A. P. and Nyunt, M. M. and Nyunt, M. H. and Brown, T. S. and Adams, M. and Pepin, C. S. and Bailey, J. and Tan, J. C. and Ferdig, M. T. and Clark, T. G. and Miotto, O. and MacInnis, B. and Kwiatkowski, D. P. and White, N. J. and Ringwald, P. and Plowe, CV} } @article {49612, title = {Microbiota that affect risk for shigellosis in children in low-income countries}, journal = {Emerg Infect DisEmerg Infect Dis}, volume = {21}, number = {2}, year = {2015}, note = {Lindsay, Brianna
Oundo, Joe
Hossain, M Anowar
Antonio, Martin
Tamboura, Boubou
Walker, Alan W
Paulson, Joseph N
Parkhill, Julian
Omore, Richard
Faruque, Abu S G
Das, Suman Kumar
Ikumapayi, Usman N
Adeyemi, Mitchell
Sanogo, Doh
Saha, Debasish
Sow, Samba
Farag, Tamer H
Nasrin, Dilruba
Li, Shan
Panchalingam, Sandra
Levine, Myron M
Kotloff, Karen
Magder, Laurence S
Hungerford, Laura
Sommerfelt, Halvor
Pop, Mihai
Nataro, James P
Stine, O Colin
U19 090873/PHS HHS/United States
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov{\textquoteright}t
Research Support, U.S. Gov{\textquoteright}t, Non-P.H.S.
United States
Emerg Infect Dis. 2015 Feb;21(2):242-50. doi: 10.3201/eid2101.140795.}, month = {Feb}, pages = {242-50}, edition = {2015/01/28}, abstract = {Pathogens in the gastrointestinal tract exist within a vast population of microbes. We examined associations between pathogens and composition of gut microbiota as they relate to Shigella spp./enteroinvasive Escherichia coli infection. We analyzed 3,035 stool specimens (1,735 nondiarrheal and 1,300 moderate-to-severe diarrheal) from the Global Enteric Multicenter Study for 9 enteropathogens. Diarrheal specimens had a higher number of enteropathogens (diarrheal mean 1.4, nondiarrheal mean 0.95; p<0.0001). Rotavirus showed a negative association with Shigella spp. in cases of diarrhea (odds ratio 0.31, 95\% CI 0.17-0.55) and had a large combined effect on moderate-to-severe diarrhea (odds ratio 29, 95\% CI 3.8-220). In 4 Lactobacillus taxa identified by 16S rRNA gene sequencing, the association between pathogen and disease was decreased, which is consistent with the possibility that Lactobacillus spp. are protective against Shigella spp.-induced diarrhea. Bacterial diversity of gut microbiota was associated with diarrhea status, not high levels of the Shigella spp. ipaH gene.}, isbn = {1080-6059 (Electronic)
1080-6040 (Linking)}, author = {Lindsay, B. and Oundo, J. and Hossain, M. A. and Antonio, M. and Tamboura, B. and Walker, A. W. and Paulson, J. N. and Parkhill, J. and Omore, R. and Faruque, A. S. and Das, S. K. and Ikumapayi, U. N. and Adeyemi, M. and Sanogo, D. and Saha, D. and Sow, S. and Farag, T. H. and Nasrin, D. and Li, S. and Panchalingam, S. and Levine, M. M. and Kotloff, K. and Magder, L. S. and Hungerford, L. and Sommerfelt, H. and Pop, M. and Nataro, J. P. and Stine, O. C.} } @article {49606, title = {Orchestrating high-throughput genomic analysis with Bioconductor.}, volume = {12}, year = {2015}, month = {2015 Feb}, pages = {115-21}, abstract = {

Bioconductor is an open-source, open-development software project for the analysis and comprehension of high-throughput data in genomics and molecular biology. The project aims to enable interdisciplinary research, collaboration and rapid development of scientific software. Based on the statistical programming language R, Bioconductor comprises 934 interoperable packages contributed by a large, diverse community of scientists. Packages cover a range of bioinformatic and statistical applications. They undergo formal initial review and continuous automated testing. We present an overview for prospective users and contributors.

}, keywords = {Computational Biology, Gene Expression Profiling, Genomics, High-Throughput Screening Assays, Programming Languages, software, User-Computer Interface}, issn = {1548-7105}, doi = {10.1038/nmeth.3252}, author = {Huber, Wolfgang and Carey, Vincent J and Gentleman, Robert and Anders, Simon and Carlson, Marc and Carvalho, Benilton S and Bravo, H{\'e}ctor Corrada and Davis, Sean and Gatto, Laurent and Girke, Thomas and Gottardo, Raphael and Hahne, Florian and Hansen, Kasper D and Irizarry, Rafael A and Lawrence, Michael and Love, Michael I and MacDonald, James and Obenchain, Valerie and Ole{\'s}, Andrzej K and Pag{\`e}s, Herv{\'e} and Reyes, Alejandro and Shannon, Paul and Smyth, Gordon K and Tenenbaum, Dan and Waldron, Levi and Morgan, Martin} } @article {49591, title = {RNA-Seq identifies novel myocardial gene expression signatures of heart failure.}, volume = {105}, year = {2015}, month = {2015 Feb}, pages = {83-9}, abstract = {

Heart failure is a complex clinical syndrome and has become the most common reason for adult hospitalization in developed countries. Two subtypes of heart failure, ischemic heart disease (ISCH) and dilated cardiomyopathy (DCM), have been studied using microarray platforms. However, microarray has limited resolution. Here we applied RNA sequencing (RNA-Seq) to identify gene signatures for heart failure from six individuals, including three controls, one ISCH and two DCM patients. Using genes identified from this small RNA-Seq dataset, we were able to accurately classify heart failure status in a much larger set of 313 individuals. The identified genes significantly overlapped with genes identified via genome-wide association studies for cardiometabolic traits and the promoters of those genes were enriched for binding sites for transcriptions factors. Our results indicate that it is possible to use RNA-Seq to classify disease status for complex diseases such as heart failure using an extremely small training dataset.

}, issn = {1089-8646}, doi = {10.1016/j.ygeno.2014.12.002}, author = {Liu, Yichuan and Morley, Michael and Brandimarto, Jeffrey and Hannenhalli, Sridhar and Hu, Yu and Ashley, Euan A and Tang, W H Wilson and Moravec, Christine S and Margulies, Kenneth B and Cappola, Thomas P and Li, Mingyao} } @article {49598, title = {Synthetic dosage lethality in the human metabolic network is highly predictive of tumor growth and cancer patient survival.}, journal = {Proc Natl Acad Sci U S A}, year = {2015}, month = {2015 Sep 14}, abstract = {

Synthetic dosage lethality (SDL) denotes a genetic interaction between two genes whereby the underexpression of gene A combined with the overexpression of gene B is lethal. SDLs offer a promising way to kill cancer cells by inhibiting the activity of SDL partners of activated oncogenes in tumors, which are often difficult to target directly. As experimental genome-wide SDL screens are still scarce, here we introduce a network-level computational modeling framework that quantitatively predicts human SDLs in metabolism. For each enzyme pair (A, B) we systematically knock out the flux through A combined with a stepwise flux increase through B and search for pairs that reduce cellular growth more than when either enzyme is perturbed individually. The predictive signal of the emerging network of 12,000 SDLs is demonstrated in five different ways. (i) It can be successfully used to predict gene essentiality in shRNA cancer cell line screens. Moving to clinical tumors, we show that (ii) SDLs are significantly underrepresented in tumors. Furthermore, breast cancer tumors with SDLs active (iii) have smaller sizes and (iv) result in increased patient survival, indicating that activation of SDLs increases cancer vulnerability. Finally, (v) patient survival improves when multiple SDLs are present, pointing to a cumulative effect. This study lays the basis for quantitative identification of cancer SDLs in a model-based mechanistic manner. The approach presented can be used to identify SDLs in species and cell types in which "omics" data necessary for data-driven identification are missing.

}, issn = {1091-6490}, doi = {10.1073/pnas.1508573112}, author = {Megchelenbrink, Wout and Katzir, Rotem and Lu, Xiaowen and Ruppin, Eytan and Notebaart, Richard A} } @article {49539, title = {Transcriptomic profiling of gene expression and RNA processing during Leishmania major differentiation.}, volume = {43}, year = {2015}, month = {2015 Aug 18}, pages = {6799-813}, abstract = {

Protozoan parasites of the genus Leishmania are the etiological agents of leishmaniasis, a group of diseases with a worldwide incidence of 0.9-1.6 million cases per year. We used RNA-seq to conduct a high-resolution transcriptomic analysis of the global changes in gene expression and RNA processing events that occur as L. major transforms from non-infective procyclic promastigotes to infective metacyclic promastigotes. Careful statistical analysis across multiple biological replicates and the removal of batch effects provided a high quality framework for comprehensively analyzing differential gene expression and transcriptome remodeling in this pathogen as it acquires its infectivity. We also identified precise 5{\textquoteright} and 3{\textquoteright} UTR boundaries for a majority of Leishmania genes and detected widespread alternative trans-splicing and polyadenylation. An investigation of possible correlations between stage-specific preferential trans-splicing or polyadenylation sites and differentially expressed genes revealed a lack of systematic association, establishing that differences in expression levels cannot be attributed to stage-regulated alternative RNA processing. Our findings build on and improve existing expression datasets and provide a substantially more detailed view of L. major biology that will inform the field and potentially provide a stronger basis for drug discovery and vaccine development efforts.

}, issn = {1362-4962}, doi = {10.1093/nar/gkv656}, author = {Dillon, Laura A L and Okrah, Kwame and Hughitt, V Keith and Suresh, Rahul and Li, Yuan and Fernandes, Maria Cecilia and Belew, A Trey and Corrada Bravo, Hector and Mosser, David M and El-Sayed, Najib M} } @article {49725, title = {A computational study of the Warburg effect identifies metabolic targets inhibiting cancer migration.}, journal = {Mol Syst Biol}, volume = {10}, year = {2014}, month = {2014}, pages = {744}, abstract = {

Over the last decade, the field of cancer metabolism has mainly focused on studying the role of tumorigenic metabolic rewiring in supporting cancer proliferation. Here, we perform the first genome-scale computational study of the metabolic underpinnings of cancer migration. We build genome-scale metabolic models of the NCI-60 cell lines that capture the Warburg effect (aerobic glycolysis) typically occurring in cancer cells. The extent of the Warburg effect in each of these cell line models is quantified by the ratio of glycolytic to oxidative ATP flux (AFR), which is found to be highly positively associated with cancer cell migration. We hence predicted that targeting genes that mitigate the Warburg effect by reducing the AFR may specifically inhibit cancer migration. By testing the anti-migratory effects of silencing such 17 top predicted genes in four breast and lung cancer cell lines, we find that up to 13 of these novel predictions significantly attenuate cell migration either in all or one cell line only, while having almost no effect on cell proliferation. Furthermore, in accordance with the predictions, a significant reduction is observed in the ratio between experimentally measured ECAR and OCR levels following these perturbations. Inhibiting anti-migratory targets is a promising future avenue in treating cancer since it may decrease cytotoxic-related side effects that plague current anti-proliferative treatments. Furthermore, it may reduce cytotoxic-related clonal selection of more aggressive cancer cells and the likelihood of emerging resistance.

}, issn = {1744-4292}, doi = {10.15252/msb.20145746}, author = {Yizhak, Keren and Le D{\'e}v{\'e}dec, Sylvia E and Rogkoti, Vasiliki Maria and Baenke, Franziska and de Boer, Vincent C and Frezza, Christian and Schulze, Almut and van de Water, Bob and Ruppin, Eytan} } @article {49611, title = {Construction of a dairy microbial genome catalog opens new perspectives for the metagenomic analysis of dairy fermented products}, journal = {BMC GenomicsBMC Genomics}, volume = {15}, number = {1}, year = {2014}, pages = {1101}, abstract = {BACKGROUND:Microbial communities of traditional cheeses are complex and insufficiently characterized. The origin, safety and functional role in cheese making of these microbial communities are still not well understood. Metagenomic analysis of these communities by high throughput shotgun sequencing is a promising approach to characterize their genomic and functional profiles. Such analyses, however, critically depend on the availability of appropriate reference genome databases against which the sequencing reads can be aligned.RESULTS:We built a reference genome catalog suitable for short read metagenomic analysis using a low-cost sequencing strategy. We selected 142 bacteria isolated from dairy products belonging to 137 different species and 67 genera, and succeeded to reconstruct the draft genome of 117 of them at a standard or high quality level, including isolates from the genera Kluyvera, Luteococcus and Marinilactibacillus, still missing from public database. To demonstrate the potential of this catalog, we analysed the microbial composition of the surface of two smear cheeses and one blue-veined cheese, and showed that a significant part of the microbiota of these traditional cheeses was composed of microorganisms newly sequenced in our study.CONCLUSIONS:Our study provides data, which combined with publicly available genome references, represents the most expansive catalog to date of cheese-associated bacteria. Using this extended dairy catalog, we revealed the presence in traditional cheese of dominant microorganisms not deliberately inoculated, mainly Gram-negative genera such as Pseudoalteromonas haloplanktis or Psychrobacter immobilis, that may contribute to the characteristics of cheese produced through traditional methods.}, isbn = {1471-2164}, author = {Almeida, Mathieu and Hebert, Agnes and Abraham, Anne-Laure and Rasmussen, Simon and Monnet, Christophe and Pons, Nicolas and Delbes, Celine and Loux, Valentin and Batto, Jean-Michel and Leonard, Pierre and Kennedy, Sean and Ehrlich, Stanislas and Pop, Mihai and Montel, Marie-Christine and Irlinger, Francoise and Renault, Pierre} } @article {38584, title = {CTCF binding site sequence differences are associated with unique regulatory and functional trends during embryonic stem cell differentiation}, journal = {Nucleic Acids ResNucleic Acids ResNucleic Acids Res}, volume = {42}, number = {2}, year = {2014}, note = {Plasschaert, Robert N
Vigneau, Sebastien
Tempera, Italo
Gupta, Ravi
Maksimoska, Jasna
Everett, Logan
Davuluri, Ramana
Mamorstein, Ronen
Lieberman, Paul M
Schultz, David
Hannenhalli, Sridhar
Bartolomei, Marisa S
eng
K99AI099153/AI/NIAID NIH HHS/
P30 CA10815/CA/NCI NIH HHS/
R01 CA140652/CA/NCI NIH HHS/
R01-GM052880/GM/NIGMS NIH HHS/
R01CA140652/CA/NCI NIH HHS/
R01GM085226/GM/NIGMS NIH HHS/
R01HD042026/HD/NICHD NIH HHS/
T32GM008216/GM/NIGMS NIH HHS/
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov{\textquoteright}t
England
2013/10/15 06:00
Nucleic Acids Res. 2014 Jan;42(2):774-89. doi: 10.1093/nar/gkt910. Epub 2013 Oct 10.}, month = {Jan}, pages = {774-89}, abstract = {CTCF (CCCTC-binding factor) is a highly conserved multifunctional DNA-binding protein with thousands of binding sites genome-wide. Our previous work suggested that differences in CTCF{\textquoteright}s binding site sequence may affect the regulation of CTCF recruitment and its function. To investigate this possibility, we characterized changes in genome-wide CTCF binding and gene expression during differentiation of mouse embryonic stem cells. After separating CTCF sites into three classes (LowOc, MedOc and HighOc) based on similarity to the consensus motif, we found that developmentally regulated CTCF binding occurs preferentially at LowOc sites, which have lower similarity to the consensus. By measuring the affinity of CTCF for selected sites, we show that sites lost during differentiation are enriched in motifs associated with weaker CTCF binding in vitro. Specifically, enrichment for T at the 18(th) position of the CTCF binding site is associated with regulated binding in the LowOc class and can predictably reduce CTCF affinity for binding sites. Finally, by comparing changes in CTCF binding with changes in gene expression during differentiation, we show that LowOc and HighOc sites are associated with distinct regulatory functions. Our results suggest that the regulatory control of CTCF is dependent in part on specific motifs within its binding site.}, keywords = {*Gene Expression Regulation, *Regulatory Elements, Transcriptional, Animals, Binding Sites, Cell Differentiation/*genetics, Cells, Cultured, Embryonic Stem Cells/cytology/*metabolism, Mice, Nucleotide Motifs, Protein Binding, Repressor Proteins/*metabolism}, isbn = {1362-4962 (Electronic)
0305-1048 (Linking)}, author = {Plasschaert, R. N. and Vigneau, S. and Tempera, I. and Gupta, R. and Maksimoska, J. and Everett, L. and Davuluri, R. and Mamorstein, R. and Lieberman, P. M. and Schultz, D. and Sridhar Hannenhalli and Bartolomei, M. S.} } @article {49600, title = {Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition.}, volume = {15}, year = {2014}, month = {2014}, pages = {R76}, abstract = {

BACKGROUND: Diarrheal diseases continue to contribute significantly to morbidity and mortality in infants and young children in developing countries. There is an urgent need to better understand the contributions of novel, potentially uncultured, diarrheal pathogens to severe diarrheal disease, as well as distortions in normal gut microbiota composition that might facilitate severe disease.

RESULTS: We use high throughput 16S rRNA gene sequencing to compare fecal microbiota composition in children under five years of age who have been diagnosed with moderate to severe diarrhea (MSD) with the microbiota from diarrhea-free controls. Our study includes 992 children from four low-income countries in West and East Africa, and Southeast Asia. Known pathogens, as well as bacteria currently not considered as important diarrhea-causing pathogens, are positively associated with MSD, and these include Escherichia/Shigella, and Granulicatella species, and Streptococcus mitis/pneumoniae groups. In both cases and controls, there tend to be distinct negative correlations between facultative anaerobic lineages and obligate anaerobic lineages. Overall genus-level microbiota composition exhibit a shift in controls from low to high levels of Prevotella and in MSD cases from high to low levels of Escherichia/Shigella in younger versus older children; however, there was significant variation among many genera by both site and age.

CONCLUSIONS: Our findings expand the current understanding of microbiota-associated diarrhea pathogenicity in young children from developing countries. Our findings are necessarily based on correlative analyses and must be further validated through epidemiological and molecular techniques.

}, keywords = {Bangladesh, Base Sequence, Case-Control Studies, Child, Preschool, Diarrhea, Infantile, Dysentery, Feces, Female, Gambia, HUMANS, Infant, Infant, Newborn, Intestines, Kenya, Male, Mali, Microbiota, Molecular Typing, Poverty, RNA, Bacterial, RNA, Ribosomal, 16S}, issn = {1474-760X}, doi = {10.1186/gb-2014-15-6-r76}, author = {Pop, Mihai and Walker, Alan W and Paulson, Joseph and Lindsay, Brianna and Antonio, Martin and Hossain, M Anowar and Oundo, Joseph and Tamboura, Boubou and Mai, Volker and Astrovskaya, Irina and Corrada Bravo, Hector and Rance, Richard and Stares, Mark and Levine, Myron M and Panchalingam, Sandra and Kotloff, Karen and Ikumapayi, Usman N and Ebruke, Chinelo and Adeyemi, Mitchell and Ahmed, Dilruba and Ahmed, Firoz and Alam, Meer Taifur and Amin, Ruhul and Siddiqui, Sabbir and Ochieng, John B and Ouma, Emmanuel and Juma, Jane and Mailu, Euince and Omore, Richard and Morris, J Glenn and Breiman, Robert F and Saha, Debasish and Parkhill, Julian and Nataro, James P and Stine, O Colin} } @article {49594, title = {An evaluation of Monte-Carlo logic and logicFS motivated by a study of the regulation of gene expression in heart failure}, volume = {41}, year = {2014}, month = {Feb-09-2014}, pages = {1956 - 1975}, issn = {0266-4763}, doi = {10.1080/02664763.2014.898133}, url = {http://www.tandfonline.com/doi/abs/10.1080/02664763.2014.898133}, author = {Lu, Yun and Hannenhalli, Sridhar and Cappola, Tom and Putt, Mary} } @article {49605, title = {Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays.}, volume = {30}, year = {2014}, month = {2014 May 15}, pages = {1363-9}, abstract = {

MOTIVATION: The recently released Infinium HumanMethylation450 array (the {\textquoteright}450k{\textquoteright} array) provides a high-throughput assay to quantify DNA methylation (DNAm) at \~{}450 000 loci across a range of genomic features. Although less comprehensive than high-throughput sequencing-based techniques, this product is more cost-effective and promises to be the most widely used DNAm high-throughput measurement technology over the next several years.

RESULTS: Here we describe a suite of computational tools that incorporate state-of-the-art statistical techniques for the analysis of DNAm data. The software is structured to easily adapt to future versions of the technology. We include methods for preprocessing, quality assessment and detection of differentially methylated regions from the kilobase to the megabase scale. We show how our software provides a powerful and flexible development platform for future methods. We also illustrate how our methods empower the technology to make discoveries previously thought to be possible only with sequencing-based methods.

AVAILABILITY AND IMPLEMENTATION: http://bioconductor.org/packages/release/bioc/html/minfi.html.

CONTACT: khansen@jhsph.edu; rafa@jimmy.harvard.edu

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

}, keywords = {Aged, algorithms, Colonic Neoplasms, DNA Methylation, Genome, High-Throughput Nucleotide Sequencing, HUMANS, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, software}, issn = {1367-4811}, doi = {10.1093/bioinformatics/btu049}, author = {Aryee, Martin J and Jaffe, Andrew E and Corrada-Bravo, Hector and Ladd-Acosta, Christine and Feinberg, Andrew P and Hansen, Kasper D and Irizarry, Rafael A} } @article {49583, title = {Network-level architecture and the evolutionary potential of underground metabolism}, volume = {111}, year = {2014}, month = {Dec-08-2014}, pages = {11762 - 11767}, issn = {0027-8424}, doi = {10.1073/pnas.1406102111}, url = {http://www.pnas.org/cgi/doi/10.1073/pnas.1406102111}, author = {Notebaart, R. A. and Szappanos, B. and Kintses, B. and Pal, F. and Gyorkei, A. and Bogos, B. and Lazar, V. and Spohn, R. and Bogos, B. and Wagner, A. and Ruppin, E. and Pal, C. and Papp, B.} } @article {49724, title = {Phenotype-based cell-specific metabolic modeling reveals metabolic liabilities of cancer.}, journal = {Elife}, volume = {3}, year = {2014}, month = {2014}, abstract = {

Utilizing molecular data to derive functional physiological models tailored for specific cancer cells can facilitate the use of individually tailored therapies. To this end we present an approach termed PRIME for generating cell-specific genome-scale metabolic models (GSMMs) based on molecular and phenotypic data. We build >280 models of normal and cancer cell-lines that successfully predict metabolic phenotypes in an individual manner. We utilize this set of cell-specific models to predict drug targets that selectively inhibit cancerous but not normal cell proliferation. The top predicted target, MLYCD, is experimentally validated and the metabolic effects of MLYCD depletion investigated. Furthermore, we tested cell-specific predicted responses to the inhibition of metabolic enzymes, and successfully inferred the prognosis of cancer patients based on their PRIME-derived individual GSMMs. These results lay a computational basis and a counterpart experimental proof of concept for future personalized metabolic modeling applications, enhancing the search for novel selective anticancer therapies.

}, keywords = {algorithms, Antineoplastic Agents, Biomarkers, Tumor, Carboxy-Lyases, Cell Line, Tumor, Cell Proliferation, Citric Acid Cycle, Fatty Acids, Gene Knockdown Techniques, Genome, Human, HUMANS, Lymphocytes, Models, Biological, Neoplasms, Oxidation-Reduction, PHENOTYPE, Precision Medicine}, issn = {2050-084X}, doi = {10.7554/eLife.03641}, author = {Yizhak, Keren and Gaude, Edoardo and Le D{\'e}v{\'e}dec, Sylvia and Waldman, Yedael Y and Stein, Gideon Y and van de Water, Bob and Frezza, Christian and Ruppin, Eytan} } @article {49607, title = {Removing batch effects for prediction problems with frozen surrogate variable analysis.}, volume = {2}, year = {2014}, month = {2014}, pages = {e561}, abstract = {

Batch effects are responsible for the failure of promising genomic prognostic signatures, major ambiguities in published genomic results, and retractions of widely-publicized findings. Batch effect corrections have been developed to remove these artifacts, but they are designed to be used in population studies. But genomic technologies are beginning to be used in clinical applications where samples are analyzed one at a time for diagnostic, prognostic, and predictive applications. There are currently no batch correction methods that have been developed specifically for prediction. In this paper, we propose an new method called frozen surrogate variable analysis (fSVA) that borrows strength from a training set for individual sample batch correction. We show that fSVA improves prediction accuracy in simulations and in public genomic studies. fSVA is available as part of the sva Bioconductor package.

}, issn = {2167-8359}, doi = {10.7717/peerj.561}, author = {Parker, Hilary S and Corrada Bravo, Hector and Leek, Jeffrey T} } @article {49608, title = {RNA-sequencing of the brain transcriptome implicates dysregulation of neuroplasticity, circadian rhythms and GTPase binding in bipolar disorder.}, volume = {19}, year = {2014}, month = {2014 Nov}, pages = {1179-85}, abstract = {

RNA-sequencing (RNA-seq) is a powerful technique to investigate the complexity of gene expression in the human brain. We used RNA-seq to survey the brain transcriptome in high-quality postmortem dorsolateral prefrontal cortex from 11 individuals diagnosed with bipolar disorder (BD) and from 11 age- and gender-matched controls. Deep sequencing was performed, with over 350 million reads per specimen. At a false discovery rate of <5\%, we detected five differentially expressed (DE) genes and 12 DE transcripts, most of which have not been previously implicated in BD. Among these, Prominin 1/CD133 and ATP-binding cassette-sub-family G-member2 (ABCG2) have important roles in neuroplasticity. We also show for the first time differential expression of long noncoding RNAs (lncRNAs) in BD. DE transcripts include those of serine/arginine-rich splicing factor 5 (SRSF5) and regulatory factor X4 (RFX4), which along with lncRNAs have a role in mammalian circadian rhythms. The DE genes were significantly enriched for several Gene Ontology categories. Of these, genes involved with GTPase binding were also enriched for BD-associated SNPs from previous genome-wide association studies, suggesting that differential expression of these genes is not simply a consequence of BD or its treatment. Many of these findings were replicated by microarray in an independent sample of 60 cases and controls. These results highlight common pathways for inherited and non-inherited influences on disease risk that may constitute good targets for novel therapies.

}, keywords = {Adult, Aged, Bipolar Disorder, Circadian Rhythm, Female, Genome-Wide Association Study, GTP Phosphohydrolases, HUMANS, Male, Meta-Analysis as Topic, Microarray Analysis, Middle Aged, Neuronal Plasticity, Polymerase Chain Reaction, Prefrontal Cortex, Principal Component Analysis, Sequence Analysis, RNA, Transcriptome, Young Adult}, issn = {1476-5578}, doi = {10.1038/mp.2013.170}, author = {Akula, N and Barb, J and Jiang, X and Wendland, J R and Choi, K H and Sen, S K and Hou, L and Chen, D T W and Laje, G and Johnson, K and Lipska, B K and Kleinman, J E and Corrada-Bravo, H and Detera-Wadleigh, S and Munson, P J and McMahon, F J} } @article {38469, title = {RNA-sequencing of the brain transcriptome implicates dysregulation of neuroplasticity, circadian rhythms and GTPase binding in bipolar disorder}, journal = {Molecular psychiatry}, year = {2014}, note = {http://www.ncbi.nlm.nih.gov/pubmed/24393808?dopt=Abstract}, type = {10.1038/mp.2013.170}, abstract = {RNA-sequencing (RNA-seq) is a powerful technique to investigate the complexity of gene expression in the human brain. We used RNA-seq to survey the brain transcriptome in high-quality postmortem dorsolateral prefrontal cortex from 11 individuals diagnosed with bipolar disorder (BD) and from 11 age- and gender-matched controls. Deep sequencing was performed, with over 350 million reads per specimen. At a false discovery rate of <5\%, we detected five differentially expressed (DE) genes and 12 DE transcripts, most of which have not been previously implicated in BD. Among these, Prominin 1/CD133 and ATP-binding cassette-sub-family G-member2 (ABCG2) have important roles in neuroplasticity. We also show for the first time differential expression of long noncoding RNAs (lncRNAs) in BD. DE transcripts include those of serine/arginine-rich splicing factor 5 (SRSF5) and regulatory factor X4 (RFX4), which along with lncRNAs have a role in mammalian circadian rhythms. The DE genes were significantly enriched for several Gene Ontology categories. Of these, genes involved with GTPase binding were also enriched for BD-associated SNPs from previous genome-wide association studies, suggesting that differential expression of these genes is not simply a consequence of BD or its treatment. Many of these findings were replicated by microarray in an independent sample of 60 cases and controls. These results highlight common pathways for inherited and non-inherited influences on disease risk that may constitute good targets for novel therapies.Molecular Psychiatry advance online publication, 7 January 2014; doi:10.1038/mp.2013.170.}, author = {Akula, N. and Barb, J. and Jiang, X. and Wendland, J. R. and Choi, K. H. and Sen, S. K. and Hou, L. and Chen, D. T. W. and Laje, G. and Johnson, K. and Lipska, B. K. and Kleinman, J. E. and H{\'e}ctor Corrada Bravo and Detera-Wadleigh, S. and Munson, P. J. and McMahon, F. J.} } @article {49614, title = {TIPP:Taxonomic Identification and Phylogenetic Profiling}, journal = {BioinformaticsBioinformatics}, year = {2014}, month = {October 29, 2014}, abstract = {Motivation: Abundance profiling (also called {\textquotedblleft}phylogenetic profiling{\textquotedblright}) is a crucial step in understanding the diversity of a metagenomic sample, and one of the basic techniques used for this is taxonomic identification of the metagenomic reads.Results: We present TIPP (taxon identification and phylogenetic profiling), a new marker-based taxon identification and abundance profiling method. TIPP combines SEPP, a phylogenetic placement method, with statistical techniques to control the classification precision and recall, and results in improved abundance profiles. TIPP is highly accurate even in the presence of high indel errors and novel genomes, and matches or improves on previous approaches, including NBC, mOTU, PhymmBL, MetaPhyler, and MetaPhlAn.Availability: Software and supplementary materials are available at http://www.cs.utexas.edu/users/phylo/software/sepp/tipp-submission/.Contact: warnow@illinois.edu}, author = {Nguyen, Nam-phuong and Mirarab, Siavash and Liu, Bo and Pop, Mihai and Warnow, Tandy} } @article {38192, title = {De novo likelihood-based measures for comparing genome assemblies}, journal = {BMC research notes}, volume = {6}, year = {2013}, publisher = {BioMed Central Ltd}, author = {Ghodsi, Mohammadreza and Christopher M. Hill and Irina Astrovskaya and Lin, Henry and Sommer, Dan D. and Koren, Sergey and M. Pop} } @article {38194, title = {A decision-theory approach to interpretable set analysis for high-dimensional data}, journal = {BiometricsBiometrics}, volume = {69}, year = {2013}, note = {http://www.ncbi.nlm.nih.gov/pubmed/23909925?dopt=Abstract}, type = {10.1111/biom.12060}, abstract = {A key problem in high-dimensional significance analysis is to find pre-defined sets that show enrichment for a statistical signal of interest; the classic example is the enrichment of gene sets for differentially expressed genes. Here, we propose a new decision-theory approach to the analysis of gene sets which focuses on estimating the fraction of non-null variables in a set. We introduce the idea of "atoms," non-overlapping sets based on the original pre-defined set annotations. Our approach focuses on finding the union of atoms that minimizes a weighted average of the number of false discoveries and missed discoveries. We introduce a new false discovery rate for sets, called the atomic false discovery rate (afdr), and prove that the optimal estimator in our decision-theory framework is to threshold the afdr. These results provide a coherent and interpretable framework for the analysis of sets that addresses the key issues of overlapping annotations and difficulty in interpreting p values in both competitive and self-contained tests. We illustrate our method and compare it to a popular existing method using simulated examples, as well as gene-set and brain ROI data analyses.}, author = {Boca, Simina M. and H{\'e}ctor Corrada Bravo and Caffo, Brian and Leek, Jeffrey T. and Parmigiani, Giovanni} } @article {38284, title = {Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia}, journal = {Proceedings of the National Academy of Sciences of the United States of AmericaProceedings of the National Academy of Sciences of the United States of America}, volume = {110}, year = {2013}, type = {10.1073/pnas.1211205110}, abstract = {The recent emergence of artemisinin-resistant Plasmodium falciparum malaria in western Cambodia could threaten prospects for malaria elimination. Identification of the genetic basis of resistance would provide tools for molecular surveillance, aiding efforts to contain resistance. Clinical trials of artesunate efficacy were conducted in Bangladesh, in northwestern Thailand near the Myanmar border, and at two sites in western Cambodia. Parasites collected from trial participants were genotyped at 8,079 single nucleotide polymorphisms (SNPs) using a P. falciparum-specific SNP array. Parasite genotypes were examined for signatures of recent positive selection and association with parasite clearance phenotypes to identify regions of the genome associated with artemisinin resistance. Four SNPs on chromosomes 10 (one), 13 (two), and 14 (one) were significantly associated with delayed parasite clearance. The two SNPs on chromosome 13 are in a region of the genome that appears to be under strong recent positive selection in Cambodia. The SNPs on chromosomes 10 and 13 lie in or near genes involved in postreplication repair, a DNA damage-tolerance pathway. Replication and validation studies are needed to refine the location of loci responsible for artemisinin resistance and to understand the mechanism behind it; however, two SNPs on chromosomes 10 and 13 may be useful markers of delayed parasite clearance in surveillance for artemisinin resistance in Southeast Asia.}, author = {Takala-Harrison, Shannon and Clark, Taane G. and Jacob, Christopher G. and Michael P. Cummings and Miotto, Olivo and Dondorp, Arjen M. and Fukuda, Mark M. and Nosten, Francois and Noedl, Harald and Imwong, Mallika and Bethell, Delia and Se, Youry and Lon, Chanthap and Tyner, Stuart D. and Saunders, David L. and Socheat, Duong and Ariey, Frederic and Phyo, Aung Pyae and Starzengruber, Peter and Fuehrer, Hans-Peter and Swoboda, Paul and Stepniewska, Kasia and Flegg, Jennifer and Arze, Cesar and Cerqueira, Gustavo C. and Silva, Joana C. and Ricklefs, Stacy M. and Porcella, Stephen F. and Stephens, Robert M. and Adams, Matthew and Kenefic, Leo J. and Campino, Susana and Auburn, Sarah and Macinnis, Bronwyn and Kwiatkowski, Dominic P. and Su, Xin-Zhuan and White, Nicholas J. and Ringwald, Pascal and Plowe, Christopher V.} } @article {38358, title = {A large-scale, higher-level, molecular phylogenetic study of the insect order Lepidoptera (moths and butterflies)}, journal = {PLoS OnePLoS One}, volume = {8}, year = {2013}, type = {10.1371/journal.pone.0058568}, abstract = {

BACKGROUND: Higher-level relationships within the Lepidoptera, and particularly within the species-rich subclade Ditrysia, are generally not well understood, although recent studies have yielded progress. We present the most comprehensive molecular analysis of lepidopteran phylogeny to date, focusing on relationships among superfamilies.

METHODOLOGY PRINCIPAL FINDINGS: 483 taxa spanning 115 of 124 families were sampled for 19 protein-coding nuclear genes, from which maximum likelihood tree estimates and bootstrap percentages were obtained using GARLI. Assessment of heuristic search effectiveness showed that better trees and higher bootstrap percentages probably remain to be discovered even after 1000 or more search replicates, but further search proved impractical even with grid computing. Other analyses explored the effects of sampling nonsynonymous change only versus partitioned and unpartitioned total nucleotide change; deletion of rogue taxa; and compositional heterogeneity. Relationships among the non-ditrysian lineages previously inferred from morphology were largely confirmed, plus some new ones, with strong support. Robust support was also found for divergences among non-apoditrysian lineages of Ditrysia, but only rarely so within Apoditrysia. Paraphyly for Tineoidea is strongly supported by analysis of nonsynonymous-only signal; conflicting, strong support for tineoid monophyly when synonymous signal was added back is shown to result from compositional heterogeneity. CONCLUSIONS SIGNIFICANCE: Support for among-superfamily relationships outside the Apoditrysia is now generally strong. Comparable support is mostly lacking within Apoditrysia, but dramatically increased bootstrap percentages for some nodes after rogue taxon removal, and concordance with other evidence, strongly suggest that our picture of apoditrysian phylogeny is approximately correct. This study highlights the challenge of finding optimal topologies when analyzing hundreds of taxa. It also shows that some nodes get strong support only when analysis is restricted to nonsynonymous change, while total change is necessary for strong support of others. Thus, multiple types of analyses will be necessary to fully resolve lepidopteran phylogeny.

}, keywords = {Animals, Butterflies, Moths, Phylogeny}, author = {Regier, Jerome C. and Mitter, Charles and Zwick, Andreas and Adam L. Bazinet and Michael P. Cummings and Kawahara, Akito Y. and Sohn, Jae-Cheon and Zwickl, Derrick J. and Cho, Soowon and Davis, Donald R. and Baixeras, Joaquin and Brown, John and Parr, Cynthia and Weller, Susan and Lees, David C. and Mitter, Kim T.} } @article {38372, title = {MetAMOS: a modular and open source metagenomic assembly and analysis pipeline}, journal = {Genome BiolGenome Biol}, volume = {14}, year = {2013}, note = {Treangen, Todd JKoren, SergeySommer, Daniel DLiu, BoAstrovskaya, IrinaOndov, BrianDarling, Aaron EPhillippy, Adam MPop, MihaiGenome Biol. 2013 Jan 15;14(1):R2.
Genome biology}, type = {10.1186/gb-2013-14-1-r2}, abstract = {ABSTRACT: We describe MetAMOS, an open source and modular metagenomic assembly and analysis pipeline. MetAMOS represents an important step towards fully automated metagenomic analysis, starting with next-generation sequencing reads and producing genomic scaffolds, open-reading frames and taxonomic or functional annotations. MetAMOS can aid in reducing assembly errors, commonly encountered when assembling metagenomic samples, and improves taxonomic assignment accuracy while also reducing computational cost. MetAMOS can be downloaded from: https://github.com/treangen/MetAMOS.}, isbn = {1465-6914 (Electronic)1465-6906 (Linking)}, author = {Todd Treangen and Koren, S. and Sommer, D. D. and Liu, B. and Irina Astrovskaya and Ondov, B. and Darling, A. E. and Phillippy, A. M. and M. Pop} } @article {38389, title = {A molecular phylogeny for Yponomeutoidea (Insecta, Lepidoptera, Ditrysia) and its implications for classification, biogeography and\ the evolution of host plant use}, journal = {PLoS One}, year = {2013}, author = {J. C. Sohn and Regier, J. C. and Mitter, C. and D. Davis and J. F. Landry and Zwick, A. and Michael P. Cummings} } @article {38455, title = {Quantitative PCR for Detection of Shigella Improves Ascertainment of Shigella Burden in Children with Moderate-to-Severe Diarrhea in Low-Income Countries}, journal = {Journal of Clinical MicrobiologyJournal of Clinical Microbiology}, volume = {51}, year = {2013}, publisher = {American Society for Microbiology}, isbn = {0095-1137}, author = {Lindsay, Brianna and Ochieng, John B. and Ikumapayi, Usman N. and Toure, Aliou and Ahmed, Dilruba and Li, Shan and Panchalingam, Sandra and Levine, Myron M. and Kotloff, Karen and Rasko, David A.} } @article {38509, title = {Somatic alterations contributing to metastasis of a castration-resistant prostate cancer}, journal = {Human mutationHuman mutation}, volume = {34}, year = {2013}, note = {http://www.ncbi.nlm.nih.gov/pubmed/23636849?dopt=Abstract}, type = {10.1002/humu.22346}, abstract = {Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease, and molecular markers that differentiate indolent from aggressive subtypes are needed. We sequenced the exomes of five metastatic tumors and healthy kidney tissue from an index case with mCRPC to identify lesions associated with disease progression and metastasis. An Ashkenazi Jewish (AJ) germline founder mutation, del185AG in BRCA1, was observed and AJ ancestry was confirmed. Sixty-two somatic variants altered proteins in tumors, including cancer-associated genes, TMPRSS2-ERG, PBRM1, and TET2. The majority (n = 53) of somatic variants were present in all metastases and only a subset (n = 31) was observed in the primary tumor. Integrating tumor next-generation sequencing and DNA copy number showed somatic loss of BRCA1 and TMPRSS2-ERG. We sequenced 19 genes with deleterious mutations in the index case in additional mCRPC samples and detected a frameshift, two somatic missense alterations, tumor loss of heterozygosity, and combinations of germline missense SNPs in TET2. In summary, genetic analysis of metastases from an index case permitted us to infer a chronology for the clonal spread of disease based on sequential accrual of somatic lesions. The role of TET2 in mCRPC deserves additional analysis and may define a subset of metastatic disease.}, author = {Nickerson, Michael L. and Im, Kate M. and Misner, Kevin J. and Tan, Wei and Lou, Hong and Gold, Bert and Wells, David W. and H{\'e}ctor Corrada Bravo and Fredrikson, Karin M. and Harkins, Timothy T. and Milos, Patrice and Zbar, Berton and Linehan, W. Marston and Yeager, Meredith and Andresson, Thorkell and Dean, Michael and Bova, G. Steven} } @article {38519, title = {Survey of Culture, GoldenGate Assay, Universal Biosensor Assay, and 16S rRNA Gene Sequencing as Alternative Methods of Bacterial Pathogen Detection}, journal = {Journal of Clinical MicrobiologyJournal of Clinical Microbiology}, volume = {51}, year = {2013}, publisher = {American Society for Microbiology}, isbn = {0095-1137}, author = {Lindsay, Brianna and M. Pop and Antonio, Martin and Walker, Alan W. and Mai, Volker and Ahmed, Dilruba and Oundo, Joseph and Tamboura, Boubou and Panchalingam, Sandra and Levine, Myron M.} } @article {38107, title = {AGORA: Assembly Guided by Optical Restriction Alignment}, journal = {BMC bioinformaticsBMC Bioinformatics}, volume = {13}, year = {2012}, publisher = {BioMed Central Ltd}, author = {Lin, H. C. and Goldstein, S. and L. Mendelowitz and Zhou, S. and Wetzel, J. and Schwartz, D. C. and M. Pop} } @article {49741, title = {BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA repression during human cytomegalovirus infection.}, journal = {Proc Natl Acad Sci U S A}, volume = {109}, year = {2012}, month = {2012 Jun 12}, pages = {9575-80}, abstract = {

Cell proteins can restrict the replication of viruses. Here, we identify the cellular BclAF1 protein as a human cytomegalovirus restriction factor and describe two independent mechanisms the virus uses to decrease its steady-state levels. Immediately following infection, the viral pp71 and UL35 proteins, which are delivered to cells within virions, direct the proteasomal degradation of BclAF1. Although BclAF1 reaccumulates through the middle stages of infection, it is subsequently down-regulated at late times by miR-UL112-1, a virus-encoded microRNA. In the absence of BclAF1 neutralization, viral gene expression and replication are inhibited. These data identify two temporally and mechanistically distinct functions used by human cytomegalovirus to down-regulate a cellular antiviral protein.

}, keywords = {Cytomegalovirus, Cytomegalovirus Infections, Genes, Immediate-Early, HUMANS, Hydrolysis, MicroRNAs, Proteasome Endopeptidase Complex, Repressor Proteins, Tumor Suppressor Proteins}, issn = {1091-6490}, doi = {10.1073/pnas.1207496109}, author = {Lee, Song Hee and Kalejta, Robert F and Kerry, Julie and Semmes, Oliver John and O{\textquoteright}Connor, Christine M and Khan, Zia and Garcia, Benjamin A and Shenk, Thomas and Murphy, Eain} } @article {49551, title = {BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA repression during human cytomegalovirus infection}, volume = {109}, year = {2012}, month = {Dec-06-2012}, pages = {9575 - 9580}, issn = {0027-8424}, doi = {10.1073/pnas.1207496109}, url = {http://www.pnas.org/cgi/doi/10.1073/pnas.1207496109}, author = {Lee, S. H. and Kalejta, R. F. and Kerry, J. and Semmes, O. J. and O{\textquoteright}Connor, C. M. and Khan, Z. and Garcia, B. A. and Shenk, T. and Murphy, E.} } @article {49550, title = {BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA repression during human cytomegalovirus infection}, journal = {Proceedings of the National Academy of Sciences}, volume = {109}, year = {2012}, month = {Dec-06-2012}, pages = {9575 - 9580}, issn = {0027-8424}, doi = {10.1073/pnas.1207496109}, url = {http://www.pnas.org/cgi/doi/10.1073/pnas.1207496109}, author = {Lee, S. H. and Kalejta, R. F. and Kerry, J. and Semmes, O. J. and O{\textquoteright}Connor, C. M. and Khan, Z. and Garcia, B. A. and Shenk, T. and Murphy, E.} } @article {38128, title = {BEAGLE: An Application Programming Interface and High-Performance Computing Library for Statistical Phylogenetics}, journal = {Systematic BiologySyst BiolSystematic BiologySyst Biol}, volume = {61}, year = {2012}, type = {10.1093/sysbio/syr100}, abstract = {Phylogenetic inference is fundamental to our understanding of most aspects of the origin and evolution of life, and in recent years, there has been a concentration of interest in statistical approaches such as Bayesian inference and maximum likelihood estimation. Yet, for large data sets and realistic or interesting models of evolution, these approaches remain computationally demanding. High-throughput sequencing can yield data for thousands of taxa, but scaling to such problems using serial computing often necessitates the use of nonstatistical or approximate approaches. The recent emergence of graphics processing units (GPUs) provides an opportunity to leverage their excellent floating-point computational performance to accelerate statistical phylogenetic inference. A specialized library for phylogenetic calculation would allow existing software packages to make more effective use of available computer hardware, including GPUs. Adoption of a common library would also make it easier for other emerging computing architectures, such as field programmable gate arrays, to be used in the future. We present BEAGLE, an application programming interface (API) and library for high-performance statistical phylogenetic inference. The API provides a uniform interface for performing phylogenetic likelihood calculations on a variety of compute hardware platforms. The library includes a set of efficient implementations and can currently exploit hardware including GPUs using NVIDIA CUDA, central processing units (CPUs) with Streaming SIMD Extensions and related processor supplementary instruction sets, and multicore CPUs via OpenMP. To demonstrate the advantages of a common API, we have incorporated the library into several popular phylogenetic software packages. The BEAGLE library is free open source software licensed under the Lesser GPL and available from http://beagle-lib.googlecode.com. An example client program is available as public domain software.}, keywords = {Bayesian phylogenetics, gpu, maximum likelihood, parallel computing}, isbn = {1063-5157, 1076-836X}, author = {Ayres, Daniel L. and Darling, Aaron and Zwickl, Derrick J. and Beerli, Peter and Holder, Mark T. and Lewis, Paul O. and Huelsenbeck, John P. and Ronquist, Fredrik and Swofford, David L. and Michael P. Cummings and Rambaut, Andrew and Suchard, Marc A.} } @article {38195, title = {Deep Sequencing of the Oral Microbiome Reveals Signatures of Periodontal Disease}, journal = {PloS onePLoS One}, volume = {7}, year = {2012}, publisher = {Public Library of Science}, author = {Liu, B. and Faller, L. L. and Klitgord, N. and Mazumdar, V. and Ghodsi, M. and Sommer, D. D. and Gibbons, T. R. and Todd Treangen and Chang, Y. C. and Li, S. and others,} } @article {49553, title = {Drosophila Src regulates anisotropic apical surface growth to control epithelial tube size}, volume = {14}, year = {2012}, month = {Jan-03-2014}, pages = {518 - 525}, issn = {1465-7392}, doi = {10.1038/ncb2467}, url = {http://www.nature.com/doifinder/10.1038/ncb2467}, author = {Nelson, Kevin S. and Khan, Zia and {\'a}r, Imre and {\'a}ly, {\'o}zsef and Kaschube, Matthias and Beitel, Greg J.} } @article {38276, title = {Gene expression anti-profiles as a basis for accurate universal cancer signatures}, journal = {BMC bioinformaticsBMC Bioinformatics}, volume = {13}, year = {2012}, note = {http://www.ncbi.nlm.nih.gov/pubmed/23088656?dopt=Abstract}, type = {10.1186/1471-2105-13-272}, abstract = {BACKGROUND: Early screening for cancer is arguably one of the greatest public health advances over the last fifty years. However, many cancer screening tests are invasive (digital rectal exams), expensive (mammograms, imaging) or both (colonoscopies). This has spurred growing interest in developing genomic signatures that can be used for cancer diagnosis and prognosis. However, progress has been slowed by heterogeneity in cancer profiles and the lack of effective computational prediction tools for this type of data. RESULTS: We developed anti-profiles as a first step towards translating experimental findings suggesting that stochastic across-sample hyper-variability in the expression of specific genes is a stable and general property of cancer into predictive and diagnostic signatures. Using single-chip microarray normalization and quality assessment methods, we developed an anti-profile for colon cancer in tissue biopsy samples. To demonstrate the translational potential of our findings, we applied the signature developed in the tissue samples, without any further retraining or normalization, to screen patients for colon cancer based on genomic measurements from peripheral blood in an independent study (AUC of 0.89). This method achieved higher accuracy than the signature underlying commercially available peripheral blood screening tests for colon cancer (AUC of 0.81). We also confirmed the existence of hyper-variable genes across a range of cancer types and found that a significant proportion of tissue-specific genes are hyper-variable in cancer. Based on these observations, we developed a universal cancer anti-profile that accurately distinguishes cancer from normal regardless of tissue type (ten-fold cross-validation AUC > 0.92). CONCLUSIONS: We have introduced anti-profiles as a new approach for developing cancer genomic signatures that specifically takes advantage of gene expression heterogeneity. We have demonstrated that anti-profiles can be successfully applied to develop peripheral-blood based diagnostics for cancer and used anti-profiles to develop a highly accurate universal cancer signature. By using single-chip normalization and quality assessment methods, no further retraining of signatures developed by the anti-profile approach would be required before their application in clinical settings. Our results suggest that anti-profiles may be used to develop inexpensive and non-invasive universal cancer screening tests.}, keywords = {Area Under Curve, Colonic Neoplasms, Gene Expression Profiling, Genetic Variation, Genomics, HUMANS, Oligonucleotide Array Sequence Analysis, Prognosis, Transcriptome, Tumor Markers, Biological}, author = {H{\'e}ctor Corrada Bravo and Pihur, Vasyl and McCall, Matthew and Irizarry, Rafael A. and Leek, Jeffrey T.} } @article {38277, title = {Gene Prediction with Glimmer for Metagenomic Sequences Augmented by Classification and Clustering}, journal = {Nucleic Acids ResearchNucl. Acids Res.Nucleic Acids ResearchNucl. Acids Res.}, volume = {40}, year = {2012}, type = {10.1093/nar/gkr1067}, abstract = {Environmental shotgun sequencing (or metagenomics) is widely used to survey the communities of microbial organisms that live in many diverse ecosystems, such as the human body. Finding the protein-coding genes within the sequences is an important step for assessing the functional capacity of a metagenome. In this work, we developed a metagenomics gene prediction system Glimmer-MG that achieves significantly greater accuracy than previous systems via novel approaches to a number of important prediction subtasks. First, we introduce the use of phylogenetic classifications of the sequences to model parameterization. We also cluster the sequences, grouping together those that likely originated from the same organism. Analogous to iterative schemes that are useful for whole genomes, we retrain our models within each cluster on the initial gene predictions before making final predictions. Finally, we model both insertion/deletion and substitution sequencing errors using a different approach than previous software, allowing Glimmer-MG to change coding frame or pass through stop codons by predicting an error. In a comparison among multiple gene finding methods, Glimmer-MG makes the most sensitive and precise predictions on simulated and real metagenomes for all read lengths and error rates tested.}, isbn = {0305-1048, 1362-4962}, author = {Kelley, David R. and Liu, Bo and Delcher, Arthur L. and M. Pop and Salzberg, Steven L.} } @article {38314, title = {Genomic analysis of sleep deprivation reveals translational regulation in the hippocampus}, journal = {Physiological GenomicsPhysiological Genomics}, year = {2012}, author = {Christopher, G. Vecsey and Lucia, Peixoto and Jennifer, H. K. Choi and Mathieu, Wimmer and Devan, Jaganath and Pepe, J. Hernandez and Jennifer, Blackwell and Karuna, Meda and Alan, J. Park and Sridhar Hannenhalli and Abel, Ted} } @article {49774, title = {Genomic insights to SAR86, an abundant and uncultivated marine bacterial lineage.}, journal = {ISME J}, volume = {6}, year = {2012}, month = {2012 Jun}, pages = {1186-99}, abstract = {

Bacteria in the 16S rRNA clade SAR86 are among the most abundant uncultivated constituents of microbial assemblages in the surface ocean for which little genomic information is currently available. Bioinformatic techniques were used to assemble two nearly complete genomes from marine metagenomes and single-cell sequencing provided two more partial genomes. Recruitment of metagenomic data shows that these SAR86 genomes substantially increase our knowledge of non-photosynthetic bacteria in the surface ocean. Phylogenomic analyses establish SAR86 as a basal and divergent lineage of γ-proteobacteria, and the individual genomes display a temperature-dependent distribution. Modestly sized at 1.25-1.7 Mbp, the SAR86 genomes lack several pathways for amino-acid and vitamin synthesis as well as sulfate reduction, trends commonly observed in other abundant marine microbes. SAR86 appears to be an aerobic chemoheterotroph with the potential for proteorhodopsin-based ATP generation, though the apparent lack of a retinal biosynthesis pathway may require it to scavenge exogenously-derived pigments to utilize proteorhodopsin. The genomes contain an expanded capacity for the degradation of lipids and carbohydrates acquired using a wealth of tonB-dependent outer membrane receptors. Like the abundant planktonic marine bacterial clade SAR11, SAR86 exhibits metabolic streamlining, but also a distinct carbon compound specialization, possibly avoiding competition.

}, keywords = {Computational Biology, Gammaproteobacteria, Genome, Bacterial, Genomic Library, metagenomics, Oceans and Seas, Phylogeny, plankton, Rhodopsin, Rhodopsins, Microbial, RNA, Ribosomal, 16S, Seawater}, issn = {1751-7370}, doi = {10.1038/ismej.2011.189}, author = {Dupont, Chris L and Rusch, Douglas B and Yooseph, Shibu and Lombardo, Mary-Jane and Richter, R Alexander and Valas, Ruben and Novotny, Mark and Yee-Greenbaum, Joyclyn and Selengut, Jeremy D and Haft, Dan H and Halpern, Aaron L and Lasken, Roger S and Nealson, Kenneth and Friedman, Robert and Venter, J Craig} } @article {38316, title = {Genomic insights to SAR86, an abundant and uncultivated marine bacterial lineage}, journal = {The ISME journalThe ISME journal}, volume = {6}, year = {2012}, note = {http://www.ncbi.nlm.nih.gov/pubmed/22170421?dopt=Abstract}, type = {10.1038/ismej.2011.189}, abstract = {Bacteria in the 16S rRNA clade SAR86 are among the most abundant uncultivated constituents of microbial assemblages in the surface ocean for which little genomic information is currently available. Bioinformatic techniques were used to assemble two nearly complete genomes from marine metagenomes and single-cell sequencing provided two more partial genomes. Recruitment of metagenomic data shows that these SAR86 genomes substantially increase our knowledge of non-photosynthetic bacteria in the surface ocean. Phylogenomic analyses establish SAR86 as a basal and divergent lineage of γ-proteobacteria, and the individual genomes display a temperature-dependent distribution. Modestly sized at 1.25-1.7 Mbp, the SAR86 genomes lack several pathways for amino-acid and vitamin synthesis as well as sulfate reduction, trends commonly observed in other abundant marine microbes. SAR86 appears to be an aerobic chemoheterotroph with the potential for proteorhodopsin-based ATP generation, though the apparent lack of a retinal biosynthesis pathway may require it to scavenge exogenously-derived pigments to utilize proteorhodopsin. The genomes contain an expanded capacity for the degradation of lipids and carbohydrates acquired using a wealth of tonB-dependent outer membrane receptors. Like the abundant planktonic marine bacterial clade SAR11, SAR86 exhibits metabolic streamlining, but also a distinct carbon compound specialization, possibly avoiding competition.}, keywords = {Computational Biology, Gammaproteobacteria, Genome, Bacterial, Genomic Library, metagenomics, Oceans and Seas, Phylogeny, plankton, Rhodopsin, RNA, Ribosomal, 16S, Seawater}, author = {Dupont, Chris L. and Rusch, Douglas B. and Yooseph, Shibu and Lombardo, Mary-Jane and Richter, R. Alexander and Valas, Ruben and Novotny, Mark and Yee-Greenbaum, Joyclyn and J. Selengut and Haft, Dan H. and Halpern, Aaron L. and Lasken, Roger S. and Nealson, Kenneth and Friedman, Robert and Venter, J. Craig} } @article {49740, title = {Global secretome analysis identifies novel mediators of bone metastasis.}, journal = {Cell Res}, volume = {22}, year = {2012}, month = {2012 Sep}, pages = {1339-55}, abstract = {

Bone is the one of the most common sites of distant metastasis of solid tumors. Secreted proteins are known to influence pathological interactions between metastatic cancer cells and the bone stroma. To comprehensively profile secreted proteins associated with bone metastasis, we used quantitative and non-quantitative mass spectrometry to globally analyze the secretomes of nine cell lines of varying bone metastatic ability from multiple species and cancer types. By comparing the secretomes of parental cells and their bone metastatic derivatives, we identified the secreted proteins that were uniquely associated with bone metastasis in these cell lines. We then incorporated bioinformatic analyses of large clinical metastasis datasets to obtain a list of candidate novel bone metastasis proteins of several functional classes that were strongly associated with both clinical and experimental bone metastasis. Functional validation of selected proteins indicated that in vivo bone metastasis can be promoted by high expression of (1) the salivary cystatins CST1, CST2, and CST4; (2) the plasminogen activators PLAT and PLAU; or (3) the collagen functionality proteins PLOD2 and COL6A1. Overall, our study has uncovered several new secreted mediators of bone metastasis and therefore demonstrated that secretome analysis is a powerful method for identification of novel biomarkers and candidate therapeutic targets.

}, keywords = {Animals, Biomarkers, Tumor, Bone Neoplasms, Cell Line, Tumor, Collagen Type VI, Computational Biology, HUMANS, Mass Spectrometry, Mice, Neoplasms, Plasminogen Activators, Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase, Proteome, proteomics, Salivary Cystatins}, issn = {1748-7838}, doi = {10.1038/cr.2012.89}, author = {Blanco, Mario Andres and LeRoy, Gary and Khan, Zia and Ale{\v c}kovi{\'c}, Ma{\v s}a and Zee, Barry M and Garcia, Benjamin A and Kang, Yibin} } @article {49549, title = {Global secretome analysis identifies novel mediators of bone metastasis}, volume = {22}, year = {2012}, month = {Dec-09-2012}, pages = {1339 - 1355}, issn = {1001-0602}, doi = {10.1038/cr.2012.89}, url = {http://www.nature.com/doifinder/10.1038/cr.2012.89}, author = {Blanco, Mario Andres and LeRoy, Gary and Khan, Zia and {\v c}kovi{\'c}, {\v s}a and Zee, Barry M and Garcia, Benjamin A and Kang, Yibin} } @article {38333, title = {Identification of Coli Surface Antigen 23, a Novel Adhesin of Enterotoxigenic Escherichia coli}, journal = {Infection and immunityInfection and immunity}, volume = {80}, year = {2012}, publisher = {American Society for Microbiology}, author = {Del Canto, F. and Botkin, D. J. and Valenzuela, P. and Popov, V. and Ruiz-Perez, F. and Nataro, J. P. and Levine, M. M. and Stine, O. C. and M. Pop and Torres, A. G. and others,} } @article {38352, title = {InterPro in 2011: new developments in the family and domain prediction database}, journal = {Nucleic acids researchNucleic Acids Research}, volume = {40}, year = {2012}, note = {http://www.ncbi.nlm.nih.gov/pubmed/22096229?dopt=Abstract}, type = {10.1093/nar/gkr948}, abstract = {InterPro (http://www.ebi.ac.uk/interpro/) is a database that integrates diverse information about protein families, domains and functional sites, and makes it freely available to the public via Web-based interfaces and services. Central to the database are diagnostic models, known as signatures, against which protein sequences can be searched to determine their potential function. InterPro has utility in the large-scale analysis of whole genomes and meta-genomes, as well as in characterizing individual protein sequences. Herein we give an overview of new developments in the database and its associated software since 2009, including updates to database content, curation processes and Web and programmatic interfaces.}, keywords = {Databases, Protein, Protein Structure, Tertiary, Proteins, Sequence Analysis, Protein, software, Terminology as Topic, User-Computer Interface}, author = {Hunter, Sarah and Jones, Philip and Mitchell, Alex and Apweiler, Rolf and Attwood, Teresa K. and Bateman, Alex and Bernard, Thomas and Binns, David and Bork, Peer and Burge, Sarah and de Castro, Edouard and Coggill, Penny and Corbett, Matthew and Das, Ujjwal and Daugherty, Louise and Duquenne, Lauranne and Finn, Robert D. and Fraser, Matthew and Gough, Julian and Haft, Daniel and Hulo, Nicolas and Kahn, Daniel and Kelly, Elizabeth and Letunic, Ivica and Lonsdale, David and Lopez, Rodrigo and Madera, Martin and Maslen, John and McAnulla, Craig and McDowall, Jennifer and McMenamin, Conor and Mi, Huaiyu and Mutowo-Muellenet, Prudence and Mulder, Nicola and Natale, Darren and Orengo, Christine and Pesseat, Sebastien and Punta, Marco and Quinn, Antony F. and Rivoire, Catherine and Sangrador-Vegas, Amaia and J. Selengut and Sigrist, Christian J. A. and Scheremetjew, Maxim and Tate, John and Thimmajanarthanan, Manjulapramila and Thomas, Paul D. and Wu, Cathy H. and Yeats, Corin and Yong, Siew-Yit} } @article {49765, title = {InterPro in 2011: new developments in the family and domain prediction database.}, journal = {Nucleic Acids Res}, volume = {40}, year = {2012}, month = {2012 Jan}, pages = {D306-12}, abstract = {

InterPro (http://www.ebi.ac.uk/interpro/) is a database that integrates diverse information about protein families, domains and functional sites, and makes it freely available to the public via Web-based interfaces and services. Central to the database are diagnostic models, known as signatures, against which protein sequences can be searched to determine their potential function. InterPro has utility in the large-scale analysis of whole genomes and meta-genomes, as well as in characterizing individual protein sequences. Herein we give an overview of new developments in the database and its associated software since 2009, including updates to database content, curation processes and Web and programmatic interfaces.

}, keywords = {Databases, Protein, Protein Structure, Tertiary, Proteins, Sequence Analysis, Protein, software, Terminology as Topic, User-Computer Interface}, issn = {1362-4962}, doi = {10.1093/nar/gkr948}, author = {Hunter, Sarah and Jones, Philip and Mitchell, Alex and Apweiler, Rolf and Attwood, Teresa K and Bateman, Alex and Bernard, Thomas and Binns, David and Bork, Peer and Burge, Sarah and de Castro, Edouard and Coggill, Penny and Corbett, Matthew and Das, Ujjwal and Daugherty, Louise and Duquenne, Lauranne and Finn, Robert D and Fraser, Matthew and Gough, Julian and Haft, Daniel and Hulo, Nicolas and Kahn, Daniel and Kelly, Elizabeth and Letunic, Ivica and Lonsdale, David and Lopez, Rodrigo and Madera, Martin and Maslen, John and McAnulla, Craig and McDowall, Jennifer and McMenamin, Conor and Mi, Huaiyu and Mutowo-Muellenet, Prudence and Mulder, Nicola and Natale, Darren and Orengo, Christine and Pesseat, Sebastien and Punta, Marco and Quinn, Antony F and Rivoire, Catherine and Sangrador-Vegas, Amaia and Selengut, Jeremy D and Sigrist, Christian J A and Scheremetjew, Maxim and Tate, John and Thimmajanarthanan, Manjulapramila and Thomas, Paul D and Wu, Cathy H and Yeats, Corin and Yong, Siew-Yit} } @article {49515, title = {A molecular phylogeny for the pyraloid moths (Lepidoptera: Pyraloidea) and its implications for higher-level classification}, journal = {Systematic Entomology}, volume = {37}, year = {2012}, month = {Jan-10-2012}, pages = {635 - 656}, doi = {10.1111/sen.2012.37.issue-410.1111/j.1365-3113.2012.00641.x}, url = {http://doi.wiley.com/10.1111/sen.2012.37.issue-4http://doi.wiley.com/10.1111/j.1365-3113.2012.00641.x}, author = {Regier, Jerome C. and Mitter, Charles and SOLIS, M. ALMA and HAYDEN, JAMES E. and LANDRY, BERNARD and NUSS, MATTHIAS and Simonsen, Thomas J. and Yen, Shen-Horn and Zwick, Andreas and Michael P. Cummings} } @article {49518, title = {MrBayes 3.2: Efficient Bayesian Phylogenetic Inference and Model Choice Across a Large Model Space}, journal = {Systematic Biology}, volume = {61}, year = {2012}, month = {05/2012}, pages = {539 - 542}, issn = {1076-836X}, doi = {10.1093/sysbio/sys029}, author = {F. Ronquist and Teslenko, M. and van der Mark, P. and Ayres, D. L. and Darling, A. and Hohna, S. and B. Larget and Liu, L. and Suchard, M. A. and J. P. Huelsenbeck} } @article {38393, title = {Myocardin-like Protein (MKL)-2 Regulates TGF-beta Signaling}, journal = {Embryonic Stem Cells and the Developing Vasculature DevelopmentEmbryonic Stem Cells and the Developing Vasculature Development}, year = {2012}, author = {Li, Jian and Nina, Bowens and Lan, Cheng and Mary, Chen and Sridhar Hannenhalli and Xiaohong, Zhu and Thomas, P. Cappola and Parmacek, Michael S.} } @article {49531, title = {Plasmodium falciparum merozoite surface protein 1 blocks the proinflammatory protein S100P.}, volume = {109}, year = {2012}, month = {2012 Apr 3}, pages = {5429-34}, abstract = {

The malaria parasite, Plasmodium falciparum, and the human immune system have coevolved to ensure that the parasite is not eliminated and reinfection is not resisted. This relationship is likely mediated through a myriad of host-parasite interactions, although surprisingly few such interactions have been identified. Here we show that the 33-kDa fragment of P. falciparum merozoite surface protein 1 (MSP1(33)), an abundant protein that is shed during red blood cell invasion, binds to the proinflammatory protein, S100P. MSP1(33) blocks S100P-induced NFκB activation in monocytes and chemotaxis in neutrophils. Remarkably, S100P binds to both dimorphic alleles of MSP1, estimated to have diverged >27 Mya, suggesting an ancient, conserved relationship between these parasite and host proteins that may serve to attenuate potentially damaging inflammatory responses.

}, keywords = {Amino Acid Sequence, Animals, Calcium-Binding Proteins, Chromatography, Gel, Electrophoresis, Polyacrylamide Gel, Enzyme-Linked Immunosorbent Assay, HUMANS, Merozoite Surface Protein 1, Microscopy, Confocal, Molecular Sequence Data, Neoplasm Proteins, Plasmodium falciparum, Sequence Homology, Amino Acid, Surface Plasmon Resonance}, issn = {1091-6490}, doi = {10.1073/pnas.1202689109}, author = {Waisberg, Michael and Cerqueira, Gustavo C and Yager, Stephanie B and Francischetti, Ivo M B and Lu, Jinghua and Gera, Nidhi and Srinivasan, Prakash and Miura, Kazutoyo and Rada, Balazs and Lukszo, Jan and Barbian, Kent D and Leto, Thomas L and Porcella, Stephen F and Narum, David L and El-Sayed, Najib and Miller, Louis H and Pierce, Susan K} } @article {38573, title = {Whole genome analysis of Leptospira licerasiae provides insight into leptospiral evolution and pathogenicity}, journal = {PLoS neglected tropical diseasesPLoS neglected tropical diseases}, volume = {6}, year = {2012}, note = {http://www.ncbi.nlm.nih.gov/pubmed/23145189?dopt=Abstract}, type = {10.1371/journal.pntd.0001853}, abstract = {The whole genome analysis of two strains of the first intermediately pathogenic leptospiral species to be sequenced (Leptospira licerasiae strains VAR010 and MMD0835) provides insight into their pathogenic potential and deepens our understanding of leptospiral evolution. Comparative analysis of eight leptospiral genomes shows the existence of a core leptospiral genome comprising 1547 genes and 452 conserved genes restricted to infectious species (including L. licerasiae) that are likely to be pathogenicity-related. Comparisons of the functional content of the genomes suggests that L. licerasiae retains several proteins related to nitrogen, amino acid and carbohydrate metabolism which might help to explain why these Leptospira grow well in artificial media compared with pathogenic species. L. licerasiae strains VAR010(T) and MMD0835 possess two prophage elements. While one element is circular and shares homology with LE1 of L. biflexa, the second is cryptic and homologous to a previously identified but unnamed region in L. interrogans serovars Copenhageni and Lai. We also report a unique O-antigen locus in L. licerasiae comprised of a 6-gene cluster that is unexpectedly short compared with L. interrogans in which analogous regions may include >90 such genes. Sequence homology searches suggest that these genes were acquired by lateral gene transfer (LGT). Furthermore, seven putative genomic islands ranging in size from 5 to 36 kb are present also suggestive of antecedent LGT. How Leptospira become naturally competent remains to be determined, but considering the phylogenetic origins of the genes comprising the O-antigen cluster and other putative laterally transferred genes, L. licerasiae must be able to exchange genetic material with non-invasive environmental bacteria. The data presented here demonstrate that L. licerasiae is genetically more closely related to pathogenic than to saprophytic Leptospira and provide insight into the genomic bases for its infectiousness and its unique antigenic characteristics.}, keywords = {DNA, Bacterial, Evolution, Molecular, Gene Transfer, Horizontal, Genome, Bacterial, Genomic islands, HUMANS, Leptospira, Molecular Sequence Data, Multigene Family, Prophages, Sequence Analysis, DNA, Virulence factors}, author = {Ricaldi, Jessica N. and Fouts, Derrick E. and J. Selengut and Harkins, Derek M. and Patra, Kailash P. and Moreno, Angelo and Lehmann, Jason S. and Purushe, Janaki and Sanka, Ravi and Torres, Michael and Webster, Nicholas J. and Vinetz, Joseph M. and Matthias, Michael A.} } @article {49776, title = {Whole genome analysis of Leptospira licerasiae provides insight into leptospiral evolution and pathogenicity.}, journal = {PLoS Negl Trop Dis}, volume = {6}, year = {2012}, month = {2012}, pages = {e1853}, abstract = {

The whole genome analysis of two strains of the first intermediately pathogenic leptospiral species to be sequenced (Leptospira licerasiae strains VAR010 and MMD0835) provides insight into their pathogenic potential and deepens our understanding of leptospiral evolution. Comparative analysis of eight leptospiral genomes shows the existence of a core leptospiral genome comprising 1547 genes and 452 conserved genes restricted to infectious species (including L. licerasiae) that are likely to be pathogenicity-related. Comparisons of the functional content of the genomes suggests that L. licerasiae retains several proteins related to nitrogen, amino acid and carbohydrate metabolism which might help to explain why these Leptospira grow well in artificial media compared with pathogenic species. L. licerasiae strains VAR010(T) and MMD0835 possess two prophage elements. While one element is circular and shares homology with LE1 of L. biflexa, the second is cryptic and homologous to a previously identified but unnamed region in L. interrogans serovars Copenhageni and Lai. We also report a unique O-antigen locus in L. licerasiae comprised of a 6-gene cluster that is unexpectedly short compared with L. interrogans in which analogous regions may include >90 such genes. Sequence homology searches suggest that these genes were acquired by lateral gene transfer (LGT). Furthermore, seven putative genomic islands ranging in size from 5 to 36 kb are present also suggestive of antecedent LGT. How Leptospira become naturally competent remains to be determined, but considering the phylogenetic origins of the genes comprising the O-antigen cluster and other putative laterally transferred genes, L. licerasiae must be able to exchange genetic material with non-invasive environmental bacteria. The data presented here demonstrate that L. licerasiae is genetically more closely related to pathogenic than to saprophytic Leptospira and provide insight into the genomic bases for its infectiousness and its unique antigenic characteristics.

}, keywords = {DNA, Bacterial, Evolution, Molecular, Gene Transfer, Horizontal, Genome, Bacterial, Genomic islands, HUMANS, Leptospira, Molecular Sequence Data, Multigene Family, Prophages, Sequence Analysis, DNA, Virulence factors}, issn = {1935-2735}, doi = {10.1371/journal.pntd.0001853}, author = {Ricaldi, Jessica N and Fouts, Derrick E and Selengut, Jeremy D and Harkins, Derek M and Patra, Kailash P and Moreno, Angelo and Lehmann, Jason S and Purushe, Janaki and Sanka, Ravi and Torres, Michael and Webster, Nicholas J and Vinetz, Joseph M and Matthias, Michael A} } @article {38102, title = {Accurate and fast estimation of taxonomic profiles from metagenomic shotgun sequences}, journal = {BMC GenomicsBMC Genomics}, volume = {12}, year = {2011}, type = {10.1186/1471-2164-12-S2-S4}, abstract = {A major goal of metagenomics is to characterize the microbial composition of an environment. The most popular approach relies on 16S rRNA sequencing, however this approach can generate biased estimates due to differences in the copy number of the gene between even closely related organisms, and due to PCR artifacts. The taxonomic composition can also be determined from metagenomic shotgun sequencing data by matching individual reads against a database of reference sequences. One major limitation of prior computational methods used for this purpose is the use of a universal classification threshold for all genes at all taxonomic levels.}, isbn = {1471-2164}, author = {Liu, Bo and Gibbons, Theodore and Ghodsi, Mohammad and Todd Treangen and M. Pop} } @article {38125, title = {Bacillus anthracis comparative genome analysis in support of the Amerithrax investigation}, journal = {Proceedings of the National Academy of SciencesProceedings of the National Academy of Sciences}, volume = {108}, year = {2011}, publisher = {National Acad Sciences}, author = {Rasko, D. A. and Worsham, P. L. and Abshire, T. G. and Stanley, S. T. and Bannan, J. D. and Wilson, M. R. and Langham, R. J. and Decker, R. S. and Jiang, L. and Read, T. D. and others,} } @article {49745, title = {A computational statistics approach for estimating the spatial range of morphogen gradients.}, journal = {Development}, volume = {138}, year = {2011}, month = {2011 Nov}, pages = {4867-74}, abstract = {

A crucial issue in studies of morphogen gradients relates to their range: the distance over which they can act as direct regulators of cell signaling, gene expression and cell differentiation. To address this, we present a straightforward statistical framework that can be used in multiple developmental systems. We illustrate the developed approach by providing a point estimate and confidence interval for the spatial range of the graded distribution of nuclear Dorsal, a transcription factor that controls the dorsoventral pattern of the Drosophila embryo.

}, keywords = {Animals, Biostatistics, Cleavage Stage, Ovum, Computational Biology, Computer simulation, Drosophila, Drosophila Proteins, Embryo, Nonmammalian, Gene Expression Regulation, Developmental, Genes, Developmental, Imaging, Three-Dimensional, In Situ Hybridization, Fluorescence, Morphogenesis, Osmolar Concentration, Tissue Distribution}, issn = {1477-9129}, doi = {10.1242/dev.071571}, author = {Kanodia, Jitendra S and Kim, Yoosik and Tomer, Raju and Khan, Zia and Chung, Kwanghun and Storey, John D and Lu, Hang and Keller, Philipp J and Shvartsman, Stanislav Y} } @article {49555, title = {A computational statistics approach for estimating the spatial range of morphogen gradients}, volume = {138}, year = {2011}, month = {Mar-11-2012}, pages = {4867 - 4874}, issn = {0950-1991}, doi = {10.1242/dev.071571}, url = {http://dev.biologists.org/cgi/doi/10.1242/dev.071571}, author = {Kanodia, J. S. and Kim, Y. and Tomer, R. and Khan, Z. and Chung, K. and Storey, J. D. and Lu, H. and Keller, P. J. and Shvartsman, S. Y.} } @article {38213, title = {DNACLUST: accurate and efficient clustering of phylogenetic marker genes}, journal = {BMC BioinformaticsBMC Bioinformatics}, volume = {12}, year = {2011}, type = {10.1186/1471-2105-12-271}, abstract = {Clustering is a fundamental operation in the analysis of biological sequence data. New DNA sequencing technologies have dramatically increased the rate at which we can generate data, resulting in datasets that cannot be efficiently analyzed by traditional clustering methods.}, isbn = {1471-2105}, author = {Ghodsi, Mohammadreza and Liu, Bo and M. Pop} } @article {38275, title = {Gene Coexpression Network Topology of Cardiac Development, Hypertrophy, and FailureClinical Perspective}, journal = {Circulation: cardiovascular geneticsCirculation: Cardiovascular Genetics}, volume = {4}, year = {2011}, publisher = {Lippincott Williams \& Wilkins}, author = {Dewey, F. E. and Perez, M. V. and Wheeler, M. T. and Watt, C. and Spin, J. and Langfelder, P. and Horvath, S. and Sridhar Hannenhalli and Cappola, T. P. and Ashley, E. A.} } @article {49651, title = {Identification of Schistosoma mansoni microRNAs.}, journal = {BMC Genomics}, volume = {12}, year = {2011}, month = {2011}, pages = {47}, abstract = {

BACKGROUND: MicroRNAs (miRNAs) constitute a class of single-stranded RNAs which play a crucial role in regulating development and controlling gene expression by targeting mRNAs and triggering either translation repression or messenger RNA (mRNA) degradation. miRNAs are widespread in eukaryotes and to date over 14,000 miRNAs have been identified by computational and experimental approaches. Several miRNAs are highly conserved across species. In Schistosoma, the full set of miRNAs and their expression patterns during development remain poorly understood. Here we report on the development and implementation of a homology-based detection strategy to search for miRNA genes in Schistosoma mansoni. In addition, we report results on the experimental detection of miRNAs by means of cDNA cloning and sequencing of size-fractionated RNA samples.

RESULTS: Homology search using the high-throughput pipeline was performed with all known miRNAs in miRBase. A total of 6,211 mature miRNAs were used as reference sequences and 110 unique S. mansoni sequences were returned by BLASTn analysis. The existing mature miRNAs that produced these hits are reported, as well as the locations of the homologous sequences in the S. mansoni genome. All BLAST hits aligned with at least 95\% of the miRNA sequence, resulting in alignment lengths of 19-24 nt. Following several filtering steps, 15 potential miRNA candidates were identified using this approach. By sequencing small RNA cDNA libraries from adult worm pairs, we identified 211 novel miRNA candidates in the S. mansoni genome. Northern blot analysis was used to detect the expression of the 30 most frequent sequenced miRNAs and to compare the expression level of these miRNAs between the lung stage schistosomula and adult worm stages. Expression of 11 novel miRNAs was confirmed by northern blot analysis and some presented a stage-regulated expression pattern. Three miRNAs previously identified from S. japonicum were also present in S. mansoni.

CONCLUSION: Evidence for the presence of miRNAs in S. mansoni is presented. The number of miRNAs detected by homology-based computational methods in S. mansoni is limited due to the lack of close relatives in the miRNA repository. In spite of this, the computational approach described here can likely be applied to the identification of pre-miRNA hairpins in other organisms. Construction and analysis of a small RNA library led to the experimental identification of 14 novel miRNAs from S. mansoni through a combination of molecular cloning, DNA sequencing and expression studies. Our results significantly expand the set of known miRNAs in multicellular parasites and provide a basis for understanding the structural and functional evolution of miRNAs in these metazoan parasites.

}, keywords = {Animals, Computational Biology, Genome, Helminth, MicroRNAs, Schistosoma mansoni}, issn = {1471-2164}, doi = {10.1186/1471-2164-12-47}, author = {Sim{\~o}es, Mariana C and Lee, Jonathan and Djikeng, Appolinaire and Cerqueira, Gustavo C and Zerlotini, Adhemar and da Silva-Pereira, Rosiane A and Dalby, Andrew R and LoVerde, Philip and El-Sayed, Najib M and Oliveira, Guilherme} } @article {38341, title = {Increased gene sampling provides stronger support for higher-level groups within gracillariid leaf mining moths and relatives (Lepidoptera: Gracillariidae)}, journal = {BMC Evol BiolBMC Evol Biol}, volume = {11:182}, year = {2011}, author = {Kawahara, A. Y. and Ohshima, I. and Kawakita, A. and Regier, J. C. and Mitter, C. and Michael P. Cummings and Davis, D. R. and Wagner, D. L. and De Prinis, J. and Lopez-Vaamonde, C.} } @article {49831, title = {Increased methylation variation in epigenetic domains across cancer types}, journal = {Nature Genetics}, volume = {43}, year = {2011}, month = {Feb-06-2013}, pages = {768 - 775}, issn = {1061-4036}, doi = {10.1038/ng.865}, url = {http://www.nature.com/doifinder/10.1038/ng.865}, author = {Hansen, Kasper Daniel and Timp, Winston and Bravo, H{\'e}ctor Corrada and Sabunciyan, Sarven and Langmead, Benjamin and McDonald, Oliver G and Wen, Bo and Wu, Hao and Liu, Yun and Diep, Dinh and Briem, Eirikur and Zhang, Kun and Irizarry, Rafael A and Feinberg, Andrew P} } @article {38373, title = {MetaPath: identifying differentially abundant metabolic pathways in metagenomic datasets}, journal = {BMC ProceedingsBMC Proceedings}, volume = {5}, year = {2011}, type = {10.1186/1753-6561-5-S2-S9}, abstract = {Enabled by rapid advances in sequencing technology, metagenomic studies aim to characterize entire communities of microbes bypassing the need for culturing individual bacterial members. One major goal of metagenomic studies is to identify specific functional adaptations of microbial communities to their habitats. The functional profile and the abundances for a sample can be estimated by mapping metagenomic sequences to the global metabolic network consisting of thousands of molecular reactions. Here we describe a powerful analytical method (MetaPath) that can identify differentially abundant pathways in metagenomic datasets, relying on a combination of metagenomic sequence data and prior metabolic pathway knowledge.}, isbn = {1753-6561}, author = {Liu, Bo and M. Pop} } @article {38460, title = {Regulation of Lung Endoderm Progenitor Cell Behavior by miR302/367}, journal = {DevelopmentDevelopmentDevelopmentDevelopment}, volume = {138}, year = {2011}, type = {10.1242/dev.061762}, abstract = {The temporal and spatial control of organ-specific endoderm progenitor development is poorly understood. miRNAs affect cell function by regulating programmatic changes in protein expression levels. We show that the miR302/367 cluster is a target of the transcription factor Gata6 in mouse lung endoderm and regulates multiple aspects of early lung endoderm progenitor development. miR302/367 is expressed at early stages of lung development, but its levels decline rapidly as development proceeds. Gain- and loss-of-function studies show that altering miR302/367 expression disrupts the balance of lung endoderm progenitor proliferation and differentiation, as well as apical-basal polarity. Increased miR302/367 expression results in the formation of an undifferentiated multi-layered lung endoderm, whereas loss of miR302/367 activity results in decreased proliferation and enhanced lung endoderm differentiation. miR302/367 coordinates the balance between proliferation and differentiation, in part, through direct regulation of Rbl2 and Cdkn1a, whereas apical-basal polarity is controlled by regulation of Tiam1 and Lis1. Thus, miR302/367 directs lung endoderm development by coordinating multiple aspects of progenitor cell behavior, including proliferation, differentiation and apical-basal polarity.}, keywords = {Lung, MicroRNA, mouse, Progenitor}, isbn = {0950-1991, 1477-9129}, author = {Tian, Ying and Zhang, Yuzhen and Hurd, Laura and Sridhar Hannenhalli and Liu, Feiyan and Lu, Min Min and Morrisey, Edward E.} } @article {38518, title = {Suppression subtractive hybridization PCR isolation of cDNAs from a Caribbean soft coral}, journal = {Electronic Journal of BiotechnologyElectronic Journal of Biotechnology}, volume = {14}, year = {2011}, publisher = {SciELO Chile}, author = {Lopez, J. V. and Ledger, A. and Santiago-V{\'a}zquez, L. Z. and M. Pop and Sommer, D. D. and Ranzer, L. K. and Feldman, R. A. and Russell, G. K.} } @article {38568, title = {Vibrio Cholerae O1 Detection in Estuarine and Coastal Zooplankton}, journal = {Journal of Plankton ResearchJ. Plankton Res.Journal of Plankton ResearchJ. Plankton Res.}, volume = {33}, year = {2011}, type = {10.1093/plankt/fbq093}, abstract = {Vibrio cholerae is an autochthonous marine bacterium, and its association with diverse planktonic crustaceans has been extensively investigated; however, the presence of V. cholerae on individuals of most phyla of planktonic animals is still incompletely understood. The objective of this study was to analyze the distribution of V. cholerae serogroup O1 associated with specific zooplankton taxa in an estuary and the adjacent continental shelf of the southeastern Brazilian coast. The occurrence of the bacterium was assessed in zooplankton samples, specifically on the most abundant taxa, using direct fluorescence assay (DFA) and direct viable count{\textendash}direct fluorescence assay (DVC{\textendash}DFA) methods. Vibrio cholerae O1 was detected in 88\% of samples collected from the Santos-Bertioga estuary and in 67\% of samples from the shelf. The salinity of the estuarine water ranged from 21.8 to 34.6, significantly lower than the shelf water which was 32.1{\textendash}36.1. Salinity was the only environmental variable measured that displayed a significant correlation with the presence of V. cholerae (P< 0.05). Vibrio cholerae O1 was detected in chaetognaths, pluteus larvae of echinoderms and planktonic fish eggs (Engraulidae), all new sites for this bacterium.}, keywords = {DFA, estuary, plankton, Southwest Atlantic}, isbn = {0142-7873, 1464-3774}, author = {Martinelli Filho, Jos{\'e} E. and Lopes, Rubens M. and Rivera, Irma N. G. and Rita R. Colwell} } @article {38210, title = {Diversity and distribution of cholix toxin, a novel ADP-ribosylating factor from Vibrio cholerae}, journal = {Environmental Microbiology ReportsEnvironmental Microbiology Reports}, volume = {2}, year = {2010}, type = {10.1111/j.1758-2229.2010.00139.x}, abstract = {Non-toxigenic non-O1, non-O139 Vibrio cholerae strains isolated from both environmental and clinical settings carry a suite of virulence factors aside from cholera toxin. Among V. cholerae strains isolated from coastal waters of southern California, this includes cholix toxin, an ADP-ribosylating factor that is capable of halting protein synthesis in eukaryotic cells. The prevalence of the gene encoding cholix toxin, chxA, was assessed among a collection of 155 diverse V. cholerae strains originating from both clinical and environmental settings in Bangladesh and Mexico and other countries around the globe. The chxA gene was present in 47\% of 83 non-O1, non-O139 strains and 16\% of 72 O1/O139 strains screened as part of this study. A total of 86 chxA gene sequences were obtained, and phylogenetic analysis revealed that they fall into two distinct clades. These two clades were also observed in the phylogenies of several housekeeping genes, suggesting that the divergence observed in chxA extends to other regions of the V. cholerae genome, and most likely has arisen from vertical descent rather than horizontal transfer. Our results clearly indicate that ChxA is a major toxin of V. cholerae with a worldwide distribution that is preferentially associated with non-pandemic strains.}, isbn = {1758-2229}, author = {Purdy, Alexandra E. and Balch, Deborah and Liz{\'a}rraga-Partida, Marcial Leonardo and Islam, Mohammad Sirajul and Martinez-Urtaza, Jaime and Huq, Anwar and Rita R. Colwell and Bartlett, Douglas H.} } @article {38222, title = {Effect on Human Cells of Environmental Vibrio Parahaemolyticus Strains Carrying Type III Secretion System 2}, journal = {Infection and ImmunityInfect. Immun.Infection and ImmunityInfect. Immun.}, volume = {78}, year = {2010}, type = {10.1128/IAI.00050-10}, abstract = {Vibrio parahaemolyticus is an inhabitant of estuarine and marine environments that causes seafood-borne gastroenteritis worldwide. Recently, a type 3 secretion system (T3SS2) able to secrete and translocate virulence factors into the eukaryotic cell has been identified in a pathogenicity island (VP-PAI) located on the smaller chromosome. These virulence-related genes have previously been detected only in clinical strains. Classical virulence genes for this species (tdh, trh) are rarely detected in environmental strains, which are usually considered to lack virulence potential. However, during screening of a collection of environmental V. parahaemolyticus isolates obtained in the North Adriatic Sea in Italy, a number of marine strains carrying virulence-related genes, including genes involved in the T3SS2, were detected. In this study, we investigated the pathogenic potential of these marine V. parahaemolyticus strains by studying their adherence ability, their cytotoxicity, their effect on zonula occludin protein 1 (ZO-1) of the tight junctions, and their effect on transepithelial resistance (TER) in infected Caco-2 cells. By performing a reverse transcription-PCR, we also tested the expression of the T3SS2 genes vopT and vopB2, encoding an effector and a translocon protein, respectively. Our results indicate that, similarly to clinical strains, marine V. parahaemolyticus strains carrying vopT and vopB2 and that other genes included in the VP-PAI are capable of adhering to human cells and of causing cytoskeletal disruption and loss of membrane integrity in infected cells. On the basis of data presented here, environmental V. parahaemolyticus strains should be included in coastal water surveillance plans, as they may represent a risk for human health.}, isbn = {0019-9567, 1098-5522}, author = {Caburlotto, Greta and Lle{\`o}, Maria M. and Hilton, Tamara and Huq, Anwar and Rita R. Colwell and Kaper, James B.} } @article {49674, title = {Evolutionary dynamics of U12-type spliceosomal introns.}, journal = {BMC Evol Biol}, volume = {10}, year = {2010}, month = {2010}, pages = {47}, abstract = {

BACKGROUND: Many multicellular eukaryotes have two types of spliceosomes for the removal of introns from messenger RNA precursors. The major (U2) spliceosome processes the vast majority of introns, referred to as U2-type introns, while the minor (U12) spliceosome removes a small fraction (less than 0.5\%) of introns, referred to as U12-type introns. U12-type introns have distinct sequence elements and usually occur together in genes with U2-type introns. A phylogenetic distribution of U12-type introns shows that the minor splicing pathway appeared very early in eukaryotic evolution and has been lost repeatedly.

RESULTS: We have investigated the evolution of U12-type introns among eighteen metazoan genomes by analyzing orthologous U12-type intron clusters. Examination of gain, loss, and type switching shows that intron type is remarkably conserved among vertebrates. Among 180 intron clusters, only eight show intron loss in any vertebrate species and only five show conversion between the U12 and the U2-type. Although there are only nineteen U12-type introns in Drosophila melanogaster, we found one case of U2 to U12-type conversion, apparently mediated by the activation of cryptic U12 splice sites early in the dipteran lineage. Overall, loss of U12-type introns is more common than conversion to U2-type and the U12 to U2 conversion occurs more frequently among introns of the GT-AG subtype than among introns of the AT-AC subtype. We also found support for natural U12-type introns with non-canonical terminal dinucleotides (CT-AC, GG-AG, and GA-AG) that have not been previously reported.

CONCLUSIONS: Although complete loss of the U12-type spliceosome has occurred repeatedly, U12 introns are extremely stable in some taxa, including eutheria. Loss of U12 introns or the genes containing them is more common than conversion to the U2-type. The degeneracy of U12-type terminal dinucleotides among natural U12-type introns is higher than previously thought.

}, keywords = {Animals, Arabidopsis, Evolution, Molecular, HUMANS, Introns, RNA, Small Nuclear, Spliceosomes}, issn = {1471-2148}, doi = {10.1186/1471-2148-10-47}, author = {Lin, Chiao-Feng and Mount, Stephen M and Jarmo{\l}owski, Artur and Maka{\l}owski, Wojciech} } @article {38282, title = {Genetic and Physiological Activation of Osmosensitive Gene Expression Mimics Transcriptional Signatures of Pathogen Infection in C. elegans}, journal = {PLoS ONEPLoS One}, volume = {5}, year = {2010}, type = {10.1371/journal.pone.0009010}, abstract = {The soil-dwelling nematode C. elegans is a powerful system for comparative molecular analyses of environmental stress response mechanisms. Infection of worms with bacterial and fungal pathogens causes the activation of well-characterized innate immune transcriptional programs in pathogen-exposed hypodermal and intestinal tissues. However, the pathophysiological events that drive such transcriptional responses are not understood. Here, we show that infection-activated transcriptional responses are, in large part, recapitulated by either physiological or genetic activation of the osmotic stress response. Microarray profiling of wild type worms exposed to non-lethal hypertonicity identified a suite of genes that were also regulated by infection. Expression profiles of five different osmotic stress resistant (osr) mutants under isotonic conditions reiterated the wild type transcriptional response to osmotic stress and also showed substantial similarity to infection-induced gene expression under isotonic conditions. Computational, transgenic, and functional approaches revealed that two GATA transcription factors previously implicated in infection-induced transcriptional responses, elt-2 and elt-3, are also essential for coordinated tissue-specific activation of osmosensitive gene expression and promote survival under osmotically stressful conditions. Together, our data suggest infection and osmotic adaptation share previously unappreciated transcriptional similarities which might be controlled via regulation of tissue-specific GATA transcription factors.}, author = {Rohlfing, Anne-Katrin and Miteva, Yana and Sridhar Hannenhalli and Lamitina, Todd} } @article {38315, title = {Genomic characterization of the Yersinia genus}, journal = {Genome BiologyGenome Biology}, volume = {11}, year = {2010}, type = {10.1186/gb-2010-11-1-r1}, abstract = {New DNA sequencing technologies have enabled detailed comparative genomic analyses of entire genera of bacterial pathogens. Prior to this study, three species of the enterobacterial genus Yersinia that cause invasive human diseases (Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica) had been sequenced. However, there were no genomic data on the Yersinia species with more limited virulence potential, frequently found in soil and water environments.}, isbn = {1465-6906}, author = {Chen, Peter E. and Cook, Christopher and Stewart, Andrew C. and Nagarajan, Niranjan and Sommer, Dan D. and M. Pop and Thomason, Brendan and Thomason, Maureen P. K. and Lentz, Shannon and Nolan, Nichole and Sozhamannan, Shanmuga and Sulakvelidze, Alexander and Mateczun, Alfred and Du, Lei and Zwick, Michael E. and Read, Timothy D.} } @article {38331, title = {Hopx and Hdac2 Interact to Modulate Gata4 Acetylation and Embryonic Cardiac Myocyte Proliferation}, journal = {Developmental CellDevelopmental Cell}, volume = {19}, year = {2010}, type = {10.1016/j.devcel.2010.08.012}, abstract = {SummaryRegulation of chromatin structure via histone modification has recently received intense attention. Here,~we demonstrate that the chromatin-modifying enzyme histone deacetylase 2 (Hdac2) functions with a small homeodomain factor, Hopx, to mediate deacetylation of Gata4, which is expressed by cardiac progenitor cells and plays critical roles in the regulation of cardiogenesis. In the absence of Hopx and Hdac2 in mouse embryos, Gata4 hyperacetylation is associated with a marked increase in~cardiac myocyte proliferation, upregulation of Gata4 target genes, and perinatal lethality. Hdac2 physically interacts with Gata4, and this interaction is stabilized by Hopx. The ability of Gata4 to transactivate cell cycle genes is impaired by Hopx/Hdac2-mediated deacetylation, and this effect is abrogated by loss of Hdac2-Gata4 interaction. These results suggest that Gata4 is a nonhistone target of Hdac2-mediated deacetylation and that Hdac2, Hopx, and Gata4 coordinately regulate cardiac myocyte proliferation during embryonic development.}, isbn = {1534-5807}, author = {Trivedi, Chinmay M. and Zhu, Wenting and Wang, Qiaohong and Jia, Cheng and Kee, Hae Jin and Li, Li and Sridhar Hannenhalli and Epstein, Jonathan A.} } @article {38335, title = {Identification of Pathogenic Vibrio Species by Multilocus PCR-Electrospray Ionization Mass Spectrometry and Its Application to Aquatic Environments of the Former Soviet Republic of Georgia}, journal = {Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol.}, volume = {76}, year = {2010}, type = {10.1128/AEM.01919-09}, abstract = {The Ibis T5000 is a novel diagnostic platform that couples PCR and mass spectrometry. In this study, we developed an assay that can identify all known pathogenic Vibrio species and field-tested it using natural water samples from both freshwater lakes and the Georgian coastal zone of the Black Sea. Of the 278 total water samples screened, 9 different Vibrio species were detected, 114 (41\%) samples were positive for V. cholerae, and 5 (0.8\%) samples were positive for the cholera toxin A gene (ctxA). All ctxA-positive samples were from two freshwater lakes, and no ctxA-positive samples from any of the Black Sea sites were detected.}, isbn = {0099-2240, 1098-5336}, author = {Whitehouse, Chris A. and Baldwin, Carson and Sampath, Rangarajan and Blyn, Lawrence B. and Melton, Rachael and Li, Feng and Hall, Thomas A. and Harpin, Vanessa and Matthews, Heather and Tediashvili, Marina and Jaiani, Ekaterina and Kokashvili, Tamar and Janelidze, Nino and Grim, Christopher and Rita R. Colwell and Huq, Anwar} } @inbook {38338, title = {Identifying Differentially Abundant Metabolic Pathways in Metagenomic Datasets}, booktitle = {Bioinformatics Research and ApplicationsBioinformatics Research and Applications}, series = {Lecture Notes in Computer Science}, volume = {6053}, year = {2010}, publisher = {Springer Berlin / Heidelberg}, organization = {Springer Berlin / Heidelberg}, abstract = {Enabled by rapid advances in sequencing technology, metagenomic studies aim to characterize entire communities of microbes bypassing the need for culturing individual bacterial members. One major goal of such studies is to identify specific functional adaptations of microbial communities to their habitats. Here we describe a powerful analytical method (MetaPath) that can identify differentially abundant pathways in metagenomic data-sets, relying on a combination of metagenomic sequence data and prior metabolic pathway knowledge. We show that MetaPath outperforms other common approaches when evaluated on simulated datasets. We also demonstrate the power of our methods in analyzing two, publicly available, metagenomic datasets: a comparison of the gut microbiome of obese and lean twins; and a comparison of the gut microbiome of infant and adult subjects. We demonstrate that the subpathways identified by our method provide valuable insights into the biological activities of the microbiome.}, isbn = {978-3-642-13077-9}, author = {Liu, Bo and M. Pop}, editor = {Borodovsky, Mark and Gogarten, Johann and Przytycka, Teresa and Rajasekaran, Sanguthevar} } @proceedings {38374, title = {MetaPhyler: Taxonomic profiling for metagenomic sequences}, year = {2010}, month = {2010}, publisher = {IEEE}, type = {10.1109/BIBM.2010.5706544}, abstract = {A major goal of metagenomics is to characterize the microbial diversity of an environment. The most popular approach relies on 16S rRNA sequencing, however this approach can generate biased estimates due to differences in the copy number of the 16S rRNA gene between even closely related organisms, and due to PCR artifacts. The taxonomic composition can also be determined from whole-metagenome sequencing data by matching individual sequences against a database of reference genes. One major limitation of prior methods used for this purpose is the use of a universal classification threshold for all genes at all taxonomic levels. We propose that better classification results can be obtained by tuning the taxonomic classifier to each matching length, reference gene, and taxonomic level. We present a novel taxonomic profiler MetaPhyler, which uses marker genes as a taxonomic reference. Results on simulated datasets demonstrate that MetaPhyler outperforms other tools commonly used in this context (CARMA, Megan and PhymmBL). We also present interesting results obtained by applying MetaPhyler to a real metagenomic dataset.}, keywords = {Bioinformatics, CARMA comparison, Databases, Genomics, Linear regression, marker genes, matching length, Megan comparison, metagenomic sequences, metagenomics, MetaPhyler, microbial diversity, microorganisms, molecular biophysics, molecular configurations, Pattern classification, pattern matching, phylogenetic classification, Phylogeny, PhymmBL comparison, reference gene database, Sensitivity, sequence matching, taxonomic classifier, taxonomic level, taxonomic profiling, whole metagenome sequencing data}, isbn = {978-1-4244-8306-8}, author = {Liu, Bo and Gibbons, T. and Ghodsi, M. and M. Pop} } @article {49650, title = {A model for using a concept inventory as a tool for students{\textquoteright} assessment and faculty professional development.}, journal = {CBE Life Sci Educ}, volume = {9}, year = {2010}, month = {2010 Winter}, pages = {408-16}, abstract = {

This essay describes how the use of a concept inventory has enhanced professional development and curriculum reform efforts of a faculty teaching community. The Host Pathogen Interactions (HPI) teaching team is composed of research and teaching faculty with expertise in HPI who share the goal of improving the learning experience of students in nine linked undergraduate microbiology courses. To support evidence-based curriculum reform, we administered our HPI Concept Inventory as a pre- and postsurvey to approximately 400 students each year since 2006. The resulting data include student scores as well as their open-ended explanations for distractor choices. The data have enabled us to address curriculum reform goals of 1) reconciling student learning with our expectations, 2) correlating student learning with background variables, 3) understanding student learning across institutions, 4) measuring the effect of teaching techniques on student learning, and 5) demonstrating how our courses collectively form a learning progression. The analysis of the concept inventory data has anchored and deepened the team{\textquoteright}s discussions of student learning. Reading and discussing students{\textquoteright} responses revealed the gap between our understanding and the students{\textquoteright} understanding. We provide evidence to support the concept inventory as a tool for assessing student understanding of HPI concepts and faculty development.

}, keywords = {Curriculum, Faculty, Models, Theoretical, Research, Students, Teaching}, issn = {1931-7913}, doi = {10.1187/cbe.10-05-0069}, author = {Marbach-Ad, Gili and McAdams, Katherine C and Benson, Spencer and Briken, Volker and Cathcart, Laura and Chase, Michael and El-Sayed, Najib M and Frauwirth, Kenneth and Fredericksen, Brenda and Joseph, Sam W and Lee, Vincent and McIver, Kevin S and Mosser, David and Quimby, B Booth and Shields, Patricia and Song, Wenxia and Stein, Daniel C and Stewart, Richard and Thompson, Katerina V and Smith, Ann C} } @article {38497, title = {Serodiversity and ecological distribution of Vibrio parahaemolyticus in the Venetian Lagoon, Northeast Italy}, journal = {Environmental Microbiology ReportsEnvironmental Microbiology Reports}, volume = {2}, year = {2010}, type = {10.1111/j.1758-2229.2009.00123.x}, abstract = {Vibrio parahaemolyticus is a natural inhabitant of estuarine and marine environments constituting part of the autochthonous microflora. This species is associated with human gastroenteritis caused by ingestion of contaminated water and undercooked seafood. During the past several years, the number of V. parahaemolyticus gastroenteritis cases have increased worldwide, causing over half of all food-poisoning outbreaks of bacterial origin. Vibrio populations in water are known to be influenced by environmental factors. Notably, it has been shown that in different parts of the world the distribution of V. parahaemolyticus in the marine environment is related to the water temperature. In this study, we identified environmental determinants affecting distribution of V. parahaemolyticus in the Venetian Lagoon, in the Italian North Adriatic Sea. Data obtained revealed that sea surface temperature constitutes the key factor influencing occurrence of V. parahaemolyticus, but salinity and chlorophyll concentration are also important. Serotyping of a collection of V. parahaemolyticus environmental isolates revealed high serodiversity, with serotypes O3:KUT and O1:KUT, belonging to the {\textquoteleft}pandemic group{\textquoteright}, occurring with higher frequency. From our results, we conclude that there is no correlation between serotype and specific geographic site or season of the year. However, certain serotypes were isolated in the Lagoon during the entire 18 months of the study, strongly suggesting persistence in this environment.}, isbn = {1758-2229}, author = {Caburlotto, Greta and Haley, Bradd J. and Lle{\`o}, Maria M. and Huq, Anwar and Rita R. Colwell} } @article {38522, title = {Tackling the widespread and critical impact of batch effects in high-throughput data}, journal = {Nature reviews. GeneticsNature reviews. Genetics}, volume = {11}, year = {2010}, note = {http://www.ncbi.nlm.nih.gov/pubmed/20838408?dopt=Abstract}, type = {10.1038/nrg2825}, abstract = {High-throughput technologies are widely used, for example to assay genetic variants, gene and protein expression, and epigenetic modifications. One often overlooked complication with such studies is batch effects, which occur because measurements are affected by laboratory conditions, reagent lots and personnel differences. This becomes a major problem when batch effects are correlated with an outcome of interest and lead to incorrect conclusions. Using both published studies and our own analyses, we argue that batch effects (as well as other technical and biological artefacts) are widespread and critical to address. We review experimental and computational approaches for doing so.}, keywords = {biotechnology, Computational Biology, Genomics, Oligonucleotide Array Sequence Analysis, Periodicals as Topic, Research Design, Sequence Analysis, DNA}, author = {Leek, Jeffrey T. and Scharpf, Robert B. and H{\'e}ctor Corrada Bravo and Simcha, David and Langmead, Benjamin and Johnson, W. Evan and Geman, Donald and Baggerly, Keith and Irizarry, Rafael A.} } @article {38561, title = {Validating the systematic position of {\i}t Plationus Segers, Murugan \& Dumont, 1993 (Rotifera: Brachionidae) using sequences of the large subunit of the nuclear ribosomal DNA and of cytochrome C oxidase}, journal = {HydrobiologiaHydrobiologia}, volume = {644}, year = {2010}, type = {DOI 10.1007/s10750-010-0203-1}, abstract = {Members of the family Brachionidae are free-living organisms that range in size from 170 to 250 microns. They comprise part of the zooplankton in freshwater and marine systems worldwide. Morphologically, members of the family are characterized by a single piece loricated body without furrows, grooves, sulci or dorsal head shields, and a malleate trophi. Differences in these structures have been traditionally used to recognize 217 species that are classified into seven genera. However, the validity of the species, Plationus patulus, P. patulus macracanthus P. polyacanthus, and P. felicitas have been confused because they were alternatively assigned in Brachionus or Platyias, when considering only morphological and ecological characters. Based on scanning electron microscope (SEM) images of the trophi, these taxa were assigned in a new genus, Plationus. In this study, we examined the systematic position of P. patulus and P. patulus macracanthus using DNA sequences of two genes: the cytochrome oxidase subunit 1 (cox1) and domains D2 and D3 of the large subunit of the nuclear ribosomal RNA (LSU). In addition, the cox1 and LSU sequences representing five genera of Brachionidae (Anuraeopsis, Brachionus, Keratella, Plationus, and Platyias) plus four species of three families from the order Ploima were used as the outgroup. The maximum likelihood (ML) analyses were conducted for each individual gene as well as for the combined (cox1 + LSU) data set. The ML tree from the combined data set yielded the family Brachionidae as a monophyletic group with weak bootstrap support (< 50\%). Five main clades in this tree had high (> 85\%) bootstrap support. The first clade was composed of three populations of P. patulus + P. patulus macracanthus. The second clade was composed of a single species of Platyias. The third clade was composed of six species of Brachionus. The fourth clade included a single species of the genus Anuraeopsis, and the fifth clade was composed of three species of the genus Keratella. The genetic divergence between Plationus and Platyias ranged from 18.4 to 19.2\% for cox1, and from 4.5 to 4.9\% for LSU, and between Brachionus and Plationus, it ranged from 16.9 to 23.1\% (cox1), and from 7.3 to 9.1\% (LSU). Morphological evidence, the amount of genetic divergence, the systematic position of Plationus within the family Brachionidae, and the position of Plationus as a sister group of Brachionus and Platyias support the validity of Plationus patulus and P. patulus macracanthus into the genus Plationus.}, keywords = {Cox1, likelihood, LSU, maximum, Phylogeny, Plationus}, author = {Reyna-Fabian, M. E. and Laclette, J. P. and Michael P. Cummings and Garc{\'\i}a-Varela, M.} } @article {38120, title = {ARDB--Antibiotic Resistance Genes Database}, journal = {Nucleic Acids ResearchNucleic Acids Research}, volume = {37}, year = {2009}, type = {10.1093/nar/gkn656}, abstract = {The treatment of infections is increasingly compromised by the ability of bacteria to develop resistance to antibiotics through mutations or through the acquisition of resistance genes. Antibiotic resistance genes also have the potential to be used for bio-terror purposes through genetically modified organisms. In order to facilitate the identification and characterization of these genes, we have created a manually curated database{\textemdash}the Antibiotic Resistance Genes Database (ARDB){\textemdash}unifying most of the publicly available information on antibiotic resistance. Each gene and resistance type is annotated with rich information, including resistance profile, mechanism of action, ontology, COG and CDD annotations, as well as external links to sequence and protein databases. Our database also supports sequence similarity searches and implements an initial version of a tool for characterizing common mutations that confer antibiotic resistance. The information we provide can be used as compendium of antibiotic resistance factors as well as to identify the resistance genes of newly sequenced genes, genomes, or metagenomes. Currently, ARDB contains resistance information for 13 293 genes, 377 types, 257 antibiotics, 632 genomes, 933 species and 124 genera. ARDB is available at http://ardb.cbcb.umd.edu/.}, isbn = {0305-1048, 1362-4962}, author = {Liu, B. and M. Pop} } @article {49645, title = {Assessing Student Understanding of Host Pathogen Interactions Using a Concept Inventory}, journal = {J. Microbiol. Biol. Ed.}, volume = {10}, year = {2009}, pages = {43-50}, author = {Marbach-Ad, G. and Briken, V. and El-Sayed, N.M. and Frauwirth, K. and Fredericksen, B. and Hutcheson, S. and Gao, L.-Y. and Joseph, S. and Lee, V. and McIver, K.S. and Mosser, D. and Quimby, B.B. and Shields, P. and Song, W. and Stein, D.C. and Yuan, R.T. and Smith, A.C.} } @article {38163, title = {Comparative genomics reveals mechanism for short-term and long-term clonal transitions in pandemic Vibrio cholerae}, journal = {Proceedings of the National Academy of SciencesProceedings of the National Academy of Sciences}, volume = {106}, year = {2009}, type = {10.1073/pnas.0907787106}, abstract = {Vibrio cholerae, the causative agent of cholera, is a bacterium autochthonous to the aquatic environment, and a serious public health threat. V. cholerae serogroup O1 is responsible for the previous two cholera pandemics, in which classical and El Tor biotypes were dominant in the sixth and the current seventh pandemics, respectively. Cholera researchers continually face newly emerging and reemerging pathogenic clones carrying diverse combinations of phenotypic and genotypic properties, which significantly hampered control of the disease. To elucidate evolutionary mechanisms governing genetic diversity of pandemic V. cholerae, we compared the genome sequences of 23 V. cholerae strains isolated from a variety of sources over the past 98 years. The genome-based phylogeny revealed 12 distinct V. cholerae lineages, of which one comprises both O1 classical and El Tor biotypes. All seventh pandemic clones share nearly identical gene content. Using analogy to influenza virology, we define the transition from sixth to seventh pandemic strains as a {\textquotedblleft}shift{\textquotedblright} between pathogenic clones belonging to the same O1 serogroup, but from significantly different phyletic lineages. In contrast, transition among clones during the present pandemic period is characterized as a {\textquotedblleft}drift{\textquotedblright} between clones, differentiated mainly by varying composition of laterally transferred genomic islands, resulting in emergence of variants, exemplified by V. cholerae O139 and V. cholerae O1 El Tor hybrid clones. Based on the comparative genomics it is concluded that V. cholerae undergoes extensive genetic recombination via lateral gene transfer, and, therefore, genome assortment, not serogroup, should be used to define pathogenic V. cholerae clones.}, isbn = {0027-8424, 1091-6490}, author = {Chun, J. and Grim, C. J. and Hasan, N. A. and Lee, J. H. and Choi, S. Y. and Haley, B. J. and Taviani, E. and Jeon, Y. S. and Kim, D. W. and Lee, J. H. and Rita R. Colwell} } @proceedings {38179, title = {A cooperative combinatorial Particle Swarm Optimization algorithm for side-chain packing}, year = {2009}, month = {2009}, publisher = {IEEE}, type = {10.1109/SIS.2009.4937840}, abstract = {Particle Swarm Optimization (PSO) is a well-known, competitive technique for numerical optimization with real-parameter representation. This paper introduces CCPSO, a new Cooperative Particle Swarm Optimization algorithm for combinatorial problems. The cooperative strategy is achieved by splitting the candidate solution vector into components, where each component is optimized by a particle. Particles move throughout a continuous space, their movements based on the influences exerted by static particles that then get feedback based on the fitness of the candidate solution. Here, the application of this technique to side-chain packing (a proteomics optimization problem) is investigated. To verify the efficiency of the proposed CCPSO algorithm, we test our algorithm on three side-chain packing problems and compare our results with the provably optimal result. Computational results show that the proposed algorithm is very competitive, obtaining a conformation with an energy value within 1\% of the provably optimal solution in many proteins.}, keywords = {Algorithm design and analysis, Amino acids, combinatorial mathematics, cooperative combinatorial particle swarm optimization algorithm, Design optimization, Encoding, Feedback, numerical optimization, Optimization methods, particle swarm optimisation, Particle swarm optimization, Partitioning algorithms, Proteins, proteomics, proteomics optimization, Robustness, side-chain packing}, isbn = {978-1-4244-2762-8}, author = {Lapizco-Encinas, G. and Kingsford, Carl and Reggia, James A.} } @article {38239, title = {Evidence for Coregulation of Myocardial Gene Expression by MEF2 and NFAT in Human Heart FailureCLINICAL PERSPECTIVE}, journal = {Circulation: Cardiovascular GeneticsCirculation: Cardiovascular Genetics}, volume = {2}, year = {2009}, publisher = {Am Heart Assoc}, author = {Putt, M. E. and Sridhar Hannenhalli and Lu, Y. and Haines, P. and Chandrupatla, H. R. and Morrisey, E. E. and Margulies, K. B. and Cappola, T. P.} } @article {49834, title = {Examining the relative influence of familial, genetic, and environmental covariate information in flexible risk models}, journal = {Proceedings of the National Academy of Sciences}, volume = {106}, year = {2009}, month = {Jul-05-2010}, pages = {8128 - 8133}, issn = {0027-8424}, doi = {10.1073/pnas.0902906106}, url = {http://www.pnas.org/cgi/doi/10.1073/pnas.0902906106https://syndication.highwire.org/content/doi/10.1073/pnas.0902906106}, author = {Bravo, H. C. and Lee, K. E. and Klein, B. E. K. and Klein, R. and Iyengar, S. K. and Wahba, G.} } @article {38278, title = {Gene Profiling of Human Adipose Tissue During Evoked Inflammation In Vivo}, journal = {DiabetesDiabetesDiabetesDiabetes}, volume = {58}, year = {2009}, type = {10.2337/db09-0256}, abstract = {OBJECTIVE Adipose inflammation plays a central role in obesity-related metabolic and cardiovascular complications. However, few human adipose-secreted proteins are known to mediate these processes. We hypothesized that microarray mRNA profiling of human adipose during evoked inflammation could identify novel adipocytokines.RESEARCH DESIGN AND METHODS Healthy human volunteers (n = 14) were treated with intravenous endotoxin (3 ng/kg lipopolysaccharide [LPS]) and underwent subcutaneous adipose biopsies before and after LPS. On Affymetrix U133Plus 2.0 arrays, adipose mRNAs modulated >1.5-fold (with P < 0.00001) were selected. SignalP 3.0 and SecretomeP 2.0 identified genes predicted to encode secreted proteins. Of these, 86 candidates were chosen for validation in adipose from an independent human endotoxemia protocol (N = 7, with 0.6 ng/kg LPS) and for exploration of cellular origin in primary human adipocytes and macrophages in vitro. RESULTS Microarray identified 776 adipose genes modulated by LPS; 298 were predicted to be secreted. Of detectable prioritized genes, 82 of 85 (96\% [95\% CI 90{\textendash}99]) were upregulated (fold changes >1.0) during the lower-dose (LPS 0.6 ng/kg) validation study and 51 of 85 (59\% [49{\textendash}70]) were induced greater than 1.5-fold. Treatment of primary adipocytes with LPS and macrophage polarization to M1 proinflammatory phenotype increased expression by 1.5-fold for 58 and 73\% of detectable genes, respectively. CONCLUSIONS We demonstrate that evoked inflammation of human adipose in vivo modulated expression of multiple genes likely secreted by adipocytes and monocytes. These included established adipocytokines and chemokines implicated in recruitment and activation of lymphocytes, adhesion molecules, antioxidants, and several novel genes with unknown function. Such candidates may represent biomarkers and therapeutic targets for obesity-related complications.}, isbn = {0012-1797, 1939-327X}, author = {Shah, Rachana and Lu, Yun and Hinkle, Christine C. and McGillicuddy, Fiona C. and Kim, Roy and Sridhar Hannenhalli and Cappola, Thomas P. and Heffron, Sean and Wang, XingMei and Mehta, Nehal N. and Putt, Mary and Reilly, Muredach P.} } @article {38290, title = {Genome assortment, not serogroup, defines Vibrio cholerae pandemic strains}, journal = {NatureNature}, year = {2009}, abstract = {Vibrio cholerae, the causative agent of cholera, is a bacterium autochthonous to the aquatic environment, and a serious public health threat. V. cholerae serogroup O1 is responsible for the previous two cholera pandemics, in which classical and El Tor biotypes were dominant in the 6th and the current 7th pandemics, respectively. Cholera researchers continually face newly emerging and re-emerging pathogenic clones carrying combinations of new serogroups as well as of phenotypic and genotypic properties. These genotype and phenotype changes have hampered control of the disease. Here we compare the complete genome sequences of 23 strains of V. cholerae isolated from a variety of sources and geographical locations over the past 98 years in an effort to elucidate the evolutionary mechanisms governing genetic diversity and genesis of new pathogenic clones. The genome-based phylogeny revealed 12 distinct V. cholerae phyletic lineages, of which one, designated the V. cholerae core genome (CG), comprises both O1 classical and EI Tor biotypes. All 7th pandemic clones share nearly identical gene content, i.e., the same genome backbone. The transition from 6th to 7th pandemic strains is defined here as a {\textquoteright}shift{\textquoteright} between pathogenic clones belonging to the same O1 serogroup, but from significantly different phyletic lineages within the CG clade. In contrast, transition among clones during the present 7th pandemic period can be characterized as a {\textquoteright}drift{\textquoteright} between clones, differentiated mainly by varying composition of laterally transferred genomic islands, resulting in emergence of variants, exemplified by V.cholerae serogroup O139 and V.cholerae O1 El Tor hybrid clones that produce cholera toxin of classical biotype. Based on the comprehensive comparative genomics presented in this study it is concluded that V. cholerae undergoes extensive genetic recombination via lateral gene transfer, and, therefore, genome assortment, not serogroup, should be used to define pathogenic V. cholerae clones.}, keywords = {59, CHOLERA, genes, Genetics, GENOTYPE, ISLANDS, ORIGIN, PHENOTYPE, PUBLIC HEALTH, recombination, STRAINS, Toxins}, author = {Brettin, Thomas S. and Bruce, David C. and Challacombe, Jean F. and Detter, John C. and Han, Cliff S. and Munik, A. C. and Chertkov, Olga and Meincke, Linda and Saunders, Elizabeth and Choi, Seon Y. and Haley, Bradd J. and Taviani, Elisa and Jeon, Yoon-Seong and Kim, Dong Wook and Lee, Jae-Hak and Walters, Ronald A. and Hug, Anwar and Rita R. Colwell} } @article {49646, title = {The genome of the blood fluke Schistosoma mansoni.}, journal = {Nature}, volume = {460}, year = {2009}, month = {2009 Jul 16}, pages = {352-8}, abstract = {

Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.

}, keywords = {Animals, Biological Evolution, Exons, Genes, Helminth, Genome, Helminth, Host-Parasite Interactions, Introns, Molecular Sequence Data, Physical Chromosome Mapping, Schistosoma mansoni, Schistosomiasis mansoni}, issn = {1476-4687}, doi = {10.1038/nature08160}, author = {Berriman, Matthew and Haas, Brian J and LoVerde, Philip T and Wilson, R Alan and Dillon, Gary P and Cerqueira, Gustavo C and Mashiyama, Susan T and Al-Lazikani, Bissan and Andrade, Luiza F and Ashton, Peter D and Aslett, Martin A and Bartholomeu, Daniella C and Blandin, Ga{\"e}lle and Caffrey, Conor R and Coghlan, Avril and Coulson, Richard and Day, Tim A and Delcher, Art and DeMarco, Ricardo and Djikeng, Appolinaire and Eyre, Tina and Gamble, John A and Ghedin, Elodie and Gu, Yong and Hertz-Fowler, Christiane and Hirai, Hirohisha and Hirai, Yuriko and Houston, Robin and Ivens, Alasdair and Johnston, David A and Lacerda, Daniela and Macedo, Camila D and McVeigh, Paul and Ning, Zemin and Oliveira, Guilherme and Overington, John P and Parkhill, Julian and Pertea, Mihaela and Pierce, Raymond J and Protasio, Anna V and Quail, Michael A and Rajandream, Marie-Ad{\`e}le and Rogers, Jane and Sajid, Mohammed and Salzberg, Steven L and Stanke, Mario and Tivey, Adrian R and White, Owen and Williams, David L and Wortman, Jennifer and Wu, Wenjie and Zamanian, Mostafa and Zerlotini, Adhemar and Fraser-Liggett, Claire M and Barrell, Barclay G and El-Sayed, Najib M} } @article {49644, title = {Genomic organization and expression profile of the mucin-associated surface protein (masp) family of the human pathogen Trypanosoma cruzi.}, journal = {Nucleic Acids Res}, volume = {37}, year = {2009}, month = {2009 Jun}, pages = {3407-17}, abstract = {

A novel large multigene family was recently identified in the human pathogen Trypanosoma cruzi, causative agent of Chagas disease, and corresponds to approximately 6\% of the parasite diploid genome. The predicted gene products, mucin-associated surface proteins (MASPs), are characterized by highly conserved N- and C-terminal domains and a strikingly variable and repetitive central region. We report here an analysis of the genomic organization and expression profile of masp genes. Masps are not randomly distributed throughout the genome but instead are clustered with genes encoding mucin and other surface protein families. Masp transcripts vary in size, are preferentially expressed during the trypomastigote stage and contain highly conserved 5{\textquoteright} and 3{\textquoteright} untranslated regions. A sequence analysis of a trypomastigote cDNA library reveals the expression of multiple masp variants with a bias towards a particular masp subgroup. Immunofluorescence assays using antibodies generated against a MASP peptide reveals that the expression of particular MASPs at the cell membrane is limited to subsets of the parasite population. Western blots of phosphatidylinositol-specific phospholipase C (PI-PLC)-treated parasites suggest that MASP may be GPI-anchored and shed into the medium culture, thus contributing to the large repertoire of parasite polypeptides that are exposed to the host immune system.

}, keywords = {3{\textquoteright} Flanking Region, 5{\textquoteright} Flanking Region, Amino Acid Sequence, Animals, Base Sequence, Conserved Sequence, Gene Expression Profiling, Genes, Protozoan, Genome, Protozoan, Membrane Proteins, Molecular Sequence Data, Mucins, Multigene Family, Protozoan Proteins, RNA, Messenger, Trypanosoma cruzi}, issn = {1362-4962}, doi = {10.1093/nar/gkp172}, author = {Bartholomeu, Daniella C and Cerqueira, Gustavo C and Le{\~a}o, Ana Carolina A and daRocha, Wanderson D and Pais, Fabiano S and Macedo, Camila and Djikeng, Appolinaire and Teixeira, Santuza M R and El-Sayed, Najib M} } @article {49781, title = {InterPro: the integrative protein signature database.}, journal = {Nucleic Acids Res}, volume = {37}, year = {2009}, month = {2009 Jan}, pages = {D211-5}, abstract = {

The InterPro database (http://www.ebi.ac.uk/interpro/) integrates together predictive models or {\textquoteright}signatures{\textquoteright} representing protein domains, families and functional sites from multiple, diverse source databases: Gene3D, PANTHER, Pfam, PIRSF, PRINTS, ProDom, PROSITE, SMART, SUPERFAMILY and TIGRFAMs. Integration is performed manually and approximately half of the total approximately 58,000 signatures available in the source databases belong to an InterPro entry. Recently, we have started to also display the remaining un-integrated signatures via our web interface. Other developments include the provision of non-signature data, such as structural data, in new XML files on our FTP site, as well as the inclusion of matchless UniProtKB proteins in the existing match XML files. The web interface has been extended and now links out to the ADAN predicted protein-protein interaction database and the SPICE and Dasty viewers. The latest public release (v18.0) covers 79.8\% of UniProtKB (v14.1) and consists of 16 549 entries. InterPro data may be accessed either via the web address above, via web services, by downloading files by anonymous FTP or by using the InterProScan search software (http://www.ebi.ac.uk/Tools/InterProScan/).

}, keywords = {Databases, Protein, Proteins, Sequence Analysis, Protein, Systems Integration}, issn = {1362-4962}, doi = {10.1093/nar/gkn785}, author = {Hunter, Sarah and Apweiler, Rolf and Attwood, Teresa K and Bairoch, Amos and Bateman, Alex and Binns, David and Bork, Peer and Das, Ujjwal and Daugherty, Louise and Duquenne, Lauranne and Finn, Robert D and Gough, Julian and Haft, Daniel and Hulo, Nicolas and Kahn, Daniel and Kelly, Elizabeth and Laugraud, Aur{\'e}lie and Letunic, Ivica and Lonsdale, David and Lopez, Rodrigo and Madera, Martin and Maslen, John and McAnulla, Craig and McDowall, Jennifer and Mistry, Jaina and Mitchell, Alex and Mulder, Nicola and Natale, Darren and Orengo, Christine and Quinn, Antony F and Selengut, Jeremy D and Sigrist, Christian J A and Thimma, Manjula and Thomas, Paul D and Valentin, Franck and Wilson, Derek and Wu, Cathy H and Yeats, Corin} } @article {38353, title = {InterPro: the integrative protein signature database}, journal = {Nucleic acids researchNucleic Acids Research}, volume = {37}, year = {2009}, note = {http://www.ncbi.nlm.nih.gov/pubmed/18940856?dopt=Abstract}, type = {10.1093/nar/gkn785}, abstract = {The InterPro database (http://www.ebi.ac.uk/interpro/) integrates together predictive models or {\textquoteright}signatures{\textquoteright} representing protein domains, families and functional sites from multiple, diverse source databases: Gene3D, PANTHER, Pfam, PIRSF, PRINTS, ProDom, PROSITE, SMART, SUPERFAMILY and TIGRFAMs. Integration is performed manually and approximately half of the total approximately 58,000 signatures available in the source databases belong to an InterPro entry. Recently, we have started to also display the remaining un-integrated signatures via our web interface. Other developments include the provision of non-signature data, such as structural data, in new XML files on our FTP site, as well as the inclusion of matchless UniProtKB proteins in the existing match XML files. The web interface has been extended and now links out to the ADAN predicted protein-protein interaction database and the SPICE and Dasty viewers. The latest public release (v18.0) covers 79.8\% of UniProtKB (v14.1) and consists of 16 549 entries. InterPro data may be accessed either via the web address above, via web services, by downloading files by anonymous FTP or by using the InterProScan search software (http://www.ebi.ac.uk/Tools/InterProScan/).}, keywords = {Databases, Protein, Proteins, Sequence Analysis, Protein, Systems Integration}, author = {Hunter, Sarah and Apweiler, Rolf and Attwood, Teresa K. and Bairoch, Amos and Bateman, Alex and Binns, David and Bork, Peer and Das, Ujjwal and Daugherty, Louise and Duquenne, Lauranne and Finn, Robert D. and Gough, Julian and Haft, Daniel and Hulo, Nicolas and Kahn, Daniel and Kelly, Elizabeth and Laugraud, Aur{\'e}lie and Letunic, Ivica and Lonsdale, David and Lopez, Rodrigo and Madera, Martin and Maslen, John and McAnulla, Craig and McDowall, Jennifer and Mistry, Jaina and Mitchell, Alex and Mulder, Nicola and Natale, Darren and Orengo, Christine and Quinn, Antony F. and J. Selengut and Sigrist, Christian J. A. and Thimma, Manjula and Thomas, Paul D. and Valentin, Franck and Wilson, Derek and Wu, Cathy H. and Yeats, Corin} } @article {38391, title = {Motifs and cis-regulatory modules mediating the expression of genes co-expressed in presynaptic neurons}, journal = {Genome BiologyGenome Biology}, volume = {10}, year = {2009}, type = {10.1186/gb-2009-10-7-r72}, abstract = {Hundreds of proteins modulate neurotransmitter release and synaptic plasticity during neuronal development and in response to synaptic activity. The expression of genes in the pre- and post-synaptic neurons is under stringent spatio-temporal control, but the mechanism underlying the neuronal expression of these genes remains largely unknown.}, isbn = {1465-6906}, author = {Liu, Rui and Sridhar Hannenhalli and Bucan, Maja} } @article {38446, title = {Predicting the distribution of Vibrio spp. in the Chesapeake Bay: a Vibrio cholerae case study}, journal = {EcoHealthEcoHealth}, volume = {6}, year = {2009}, type = {10.1007/s10393-009-0273-6}, abstract = {Vibrio cholerae, the causative agent of cholera, is a naturally occurring inhabitant of the Chesapeake Bay and serves as a predictor for other clinically important vibrios, including Vibrio parahaemolyticus and Vibrio vulnificus. A system was constructed to predict the likelihood of the presence of V. cholerae in surface waters of the Chesapeake Bay, with the goal to provide forecasts of the occurrence of this and related pathogenic Vibrio spp. Prediction was achieved by driving an available multivariate empirical habitat model estimating the probability of V. cholerae within a range of temperatures and salinities in the Bay, with hydrodynamically generated predictions of ambient temperature and salinity. The experimental predictions provided both an improved understanding of the in situ variability of V. cholerae, including identification of potential hotspots of occurrence, and usefulness as an early warning system. With further development of the system, prediction of the probability of the occurrence of related pathogenic vibrios in the Chesapeake Bay, notably V. parahaemolyticus and V. vulnificus, will be possible, as well as its transport to any geographical location where sufficient relevant data are available.}, author = {Constantin de Magny, G. and Long, W. and Brown, C. W. and Hood, R. R. and Huq, A. and Murtugudde, R. and Rita R. Colwell} } @article {38462, title = {Resistin gene variation is associated with systemic inflammation but not plasma adipokine levels, metabolic syndrome or coronary atherosclerosis in nondiabetic Caucasians}, journal = {Clinical EndocrinologyClinical Endocrinology}, volume = {70}, year = {2009}, type = {10.1111/j.1365-2265.2008.03375.x}, abstract = {Objective Resistin causes insulin resistance and diabetes in mice whereas in humans it is linked to inflammation and atherosclerosis. Few human genetic studies of resistin in inflammation and atherosclerosis have been performed. We hypothesized that the {\textendash}420C>G putative gain-of-function resistin variant would be associated with inflammatory markers and atherosclerosis but not with metabolic syndrome or adipokines in humans.Design and methods We examined the association of three resistin polymorphisms, {\textendash}852A>G, {\textendash}420C>G and +157C>T, and related haplotypes with plasma resistin, cytokines, C-reactive protein (CRP), adipokines, plasma lipoproteins, metabolic syndrome and coronary artery calcification (CAC) in nondiabetic Caucasians (n~=~851). Results Resistin levels were higher, dose-dependently, with the {\textendash}420G allele (CC 5{\textperiodcentered}9~{\textpm}~2{\textperiodcentered}7~ng/ml, GC 6{\textperiodcentered}5~{\textpm}~4{\textperiodcentered}0~ng/ml and GG 7{\textperiodcentered}2~{\textpm}~4{\textperiodcentered}8~ng/ml, trend P~=~0{\textperiodcentered}04) after age and gender adjustment [fold higher for GC~+~GG vs. CC; 1{\textperiodcentered}07~(1{\textperiodcentered}00{\textendash}1{\textperiodcentered}15), P~<~0{\textperiodcentered}05)]. The {\textendash}852A>G single nucleotide polymorphism (SNP) was associated with higher soluble tumour necrosis factor-receptor~2 (sol-TNFR2) levels in fully adjusted models [1{\textperiodcentered}06~(95\%~CI 1{\textperiodcentered}01{\textendash}1{\textperiodcentered}11), P~=~0{\textperiodcentered}01)]. The estimated resistin haplotype (GGT) was associated with sol-TNFR2 (P~=~0{\textperiodcentered}04) and the AGT haplotype was related to CRP (P~=~0{\textperiodcentered}04) in the fully adjusted models. Resistin SNPs and haplotypes were not associated with body mass index (BMI), fasting glucose, insulin resistance, metabolic syndrome, adipokines or CAC scores. Conclusions Despite modest associations with plasma resistin and inflammatory biomarkers, resistin 5' variants were not associated with metabolic parameters or coronary calcification. This suggests that resistin is an inflammatory cytokine in humans but has little influence on adiposity, metabolic syndrome or atherosclerosis.}, isbn = {1365-2265}, author = {Qasim, Atif N. and Metkus, Thomas S. and Tadesse, Mahlet and Lehrke, Michael and Restine, Stephanie and Wolfe, Megan L. and Sridhar Hannenhalli and Cappola, Thomas and Rader, Daniel J. and Reilly, Muredach P.} } @inbook {38475, title = {Salient Frame Detection for Molecular Dynamics Simulations}, booktitle = {Scientific VisualizationScientific Visualization}, year = {2009}, publisher = {Dagstuhl Seminar Proceedings 09251}, organization = {Dagstuhl Seminar Proceedings 09251}, author = {Kim, Youngmin and Patro, Robert and Ip, Cheuk Yiu and O{\textquoteright}Leary, Dianne P. and Anishkin, Andriy and Sukharev, Sergei and Varshney, Amitabh}, editor = {Ebert, D. S. and Gr, and x6f, and x, and ller, E. and Hagen, H. and Kaufman, A.} } @article {38482, title = {Searching for SNPs with cloud computing}, journal = {Genome BiologyGenome Biology}, volume = {10}, year = {2009}, type = {10.1186/gb-2009-10-11-r134}, abstract = {As DNA sequencing outpaces improvements in computer speed, there is a critical need to accelerate tasks like alignment and SNP calling. Crossbow is a cloud-computing software tool that combines the aligner Bowtie and the SNP caller SOAPsnp. Executing in parallel using Hadoop, Crossbow analyzes data comprising 38-fold coverage of the human genome in three hours using a 320-CPU cluster rented from a cloud computing service for about $85. Crossbow is available from http://bowtie-bio.sourceforge.net/crossbow/.}, isbn = {1465-6906}, author = {Langmead, Ben and Schatz, Michael C. and Jimmy, Lin and M. Pop and Salzberg, Steven L.} } @article {38498, title = {Serogroup, Virulence, and Genetic Traits of Vibrio Parahaemolyticus in the Estuarine Ecosystem of Bangladesh}, journal = {Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol.}, volume = {75}, year = {2009}, type = {10.1128/AEM.00266-09}, abstract = {Forty-two strains of Vibrio parahaemolyticus were isolated from Bay of Bengal estuaries and, with two clinical strains, analyzed for virulence, phenotypic, and molecular traits. Serological analysis indicated O8, O3, O1, and K21 to be the major O and K serogroups, respectively, and O8:K21, O1:KUT, and O3:KUT to be predominant. The K antigen(s) was untypeable, and pandemic serogroup O3:K6 was not detected. The presence of genes toxR and tlh were confirmed by PCR in all but two strains, which also lacked toxR. A total of 18 (41\%) strains possessed the virulence gene encoding thermostable direct hemolysin (TDH), and one had the TDH-related hemolysin (trh) gene, but not tdh. Ten (23\%) strains exhibited Kanagawa phenomenon that surrogates virulence, of which six, including the two clinical strains, possessed tdh. Of the 18 tdh-positive strains, 17 (94\%), including the two clinical strains, had the seromarker O8:K21, one was O9:KUT, and the single trh-positive strain was O1:KUT. None had the group-specific or ORF8 pandemic marker gene. DNA fingerprinting employing pulsed-field gel electrophoresis (PFGE) of SfiI-digested DNA and cluster analysis showed divergence among the strains. Dendrograms constructed using PFGE (SfiI) images from a soft database, including those of pandemic and nonpandemic strains of diverse geographic origin, however, showed that local strains formed a cluster, i.e., {\textquotedblleft}clonal cluster,{\textquotedblright} as did pandemic strains of diverse origin. The demonstrated prevalence of tdh-positive and diarrheagenic serogroup O8:K21 strains in coastal villages of Bangladesh indicates a significant human health risk for inhabitants.}, isbn = {0099-2240, 1098-5336}, author = {Alam, Munirul and Chowdhury, Wasimul B. and Bhuiyan, N. A. and Islam, Atiqul and Hasan, Nur A. and Nair, G. Balakrish and Watanabe, H. and Siddique, A. K. and Huq, Anwar and Sack, R. Bradley and Akhter, M. Z. and Grim, Christopher J. and Kam, K. M. and Luey, C. K. Y. and Endtz, Hubert P. and Cravioto, Alejandro and Rita R. Colwell} } @article {38553, title = {Ultrafast and memory-efficient alignment of short DNA sequences to the human genome}, journal = {Genome BiologyGenome Biology}, volume = {10}, year = {2009}, type = {10.1186/gb-2009-10-3-r25}, abstract = {Bowtie is an ultrafast, memory-efficient alignment program for aligning short DNA sequence reads to large genomes. For the human genome, Burrows-Wheeler indexing allows Bowtie to align more than 25 million reads per CPU hour with a memory footprint of approximately 1.3 gigabytes. Bowtie extends previous Burrows-Wheeler techniques with a novel quality-aware backtracking algorithm that permits mismatches. Multiple processor cores can be used simultaneously to achieve even greater alignment speeds. Bowtie is open source http://bowtie.cbcb.umd.edu.}, isbn = {1465-6906}, author = {Langmead, Ben and Trapnell, Cole and M. Pop and Salzberg, Steven L.} } @article {38169, title = {The Complete Genome Sequence of Thermococcus Onnurineus NA1 Reveals a Mixed Heterotrophic and Carboxydotrophic Metabolism}, journal = {Journal of BacteriologyJ. Bacteriol.Journal of BacteriologyJ. Bacteriol.}, volume = {190}, year = {2008}, type = {10.1128/JB.00746-08}, abstract = {Members of the genus Thermococcus, sulfur-reducing hyperthermophilic archaea, are ubiquitously present in various deep-sea hydrothermal vent systems and are considered to play a significant role in the microbial consortia. We present the complete genome sequence and feature analysis of Thermococcus onnurineus NA1 isolated from a deep-sea hydrothermal vent area, which reveal clues to its physiology. Based on results of genomic analysis, T. onnurineus NA1 possesses the metabolic pathways for organotrophic growth on peptides, amino acids, or sugars. More interesting was the discovery that the genome encoded unique proteins that are involved in carboxydotrophy to generate energy by oxidation of CO to CO2, thereby providing a mechanistic basis for growth with CO as a substrate. This lithotrophic feature in combination with carbon fixation via RuBisCO (ribulose 1,5-bisphosphate carboxylase/oxygenase) introduces a new strategy with a complementing energy supply for T. onnurineus NA1 potentially allowing it to cope with nutrient stress in the surrounding of hydrothermal vents, providing the first genomic evidence for the carboxydotrophy in Thermococcus.}, isbn = {0021-9193, 1098-5530}, author = {Lee, Hyun Sook and Kang, Sung Gyun and Bae, Seung Seob and Lim, Jae Kyu and Cho, Yona and Kim, Yun Jae and Jeon, Jeong Ho and Cha, Sun-Shin and Kwon, Kae Kyoung and Kim, Hyung-Tae and Park, Cheol-Joo and Lee, Hee-Wook and Kim, Seung Il and Jongsik, Chun and Rita R. Colwell and Kim, Sang-Jin and Lee, Jung-Hyun} } @article {49676, title = {The draft genome of the transgenic tropical fruit tree papaya (Carica papaya Linnaeus).}, journal = {Nature}, volume = {452}, year = {2008}, month = {2008 Apr 24}, pages = {991-6}, abstract = {

Papaya, a fruit crop cultivated in tropical and subtropical regions, is known for its nutritional benefits and medicinal applications. Here we report a 3x draft genome sequence of {\textquoteright}SunUp{\textquoteright} papaya, the first commercial virus-resistant transgenic fruit tree to be sequenced. The papaya genome is three times the size of the Arabidopsis genome, but contains fewer genes, including significantly fewer disease-resistance gene analogues. Comparison of the five sequenced genomes suggests a minimal angiosperm gene set of 13,311. A lack of recent genome duplication, atypical of other angiosperm genomes sequenced so far, may account for the smaller papaya gene number in most functional groups. Nonetheless, striking amplifications in gene number within particular functional groups suggest roles in the evolution of tree-like habit, deposition and remobilization of starch reserves, attraction of seed dispersal agents, and adaptation to tropical daylengths. Transgenesis at three locations is closely associated with chloroplast insertions into the nuclear genome, and with topoisomerase I recognition sites. Papaya offers numerous advantages as a system for fruit-tree functional genomics, and this draft genome sequence provides the foundation for revealing the basis of Carica{\textquoteright}s distinguishing morpho-physiological, medicinal and nutritional properties.

}, keywords = {Arabidopsis, Carica, Contig Mapping, Databases, Genetic, Genes, Plant, Genome, Plant, Molecular Sequence Data, Plants, Genetically Modified, sequence alignment, Sequence Analysis, DNA, Transcription Factors, Tropical Climate}, issn = {1476-4687}, doi = {10.1038/nature06856}, author = {Ming, Ray and Hou, Shaobin and Feng, Yun and Yu, Qingyi and Dionne-Laporte, Alexandre and Saw, Jimmy H and Senin, Pavel and Wang, Wei and Ly, Benjamin V and Lewis, Kanako L T and Salzberg, Steven L and Feng, Lu and Jones, Meghan R and Skelton, Rachel L and Murray, Jan E and Chen, Cuixia and Qian, Wubin and Shen, Junguo and Du, Peng and Eustice, Moriah and Tong, Eric and Tang, Haibao and Lyons, Eric and Paull, Robert E and Michael, Todd P and Wall, Kerr and Rice, Danny W and Albert, Henrik and Wang, Ming-Li and Zhu, Yun J and Schatz, Michael and Nagarajan, Niranjan and Acob, Ricelle A and Guan, Peizhu and Blas, Andrea and Wai, Ching Man and Ackerman, Christine M and Ren, Yan and Liu, Chao and Wang, Jianmei and Wang, Jianping and Na, Jong-Kuk and Shakirov, Eugene V and Haas, Brian and Thimmapuram, Jyothi and Nelson, David and Wang, Xiyin and Bowers, John E and Gschwend, Andrea R and Delcher, Arthur L and Singh, Ratnesh and Suzuki, Jon Y and Tripathi, Savarni and Neupane, Kabi and Wei, Hairong and Irikura, Beth and Paidi, Maya and Jiang, Ning and Zhang, Wenli and Presting, Gernot and Windsor, Aaron and Navajas-P{\'e}rez, Rafael and Torres, Manuel J and Feltus, F Alex and Porter, Brad and Li, Yingjun and Burroughs, A Max and Luo, Ming-Cheng and Liu, Lei and Christopher, David A and Mount, Stephen M and Moore, Paul H and Sugimura, Tak and Jiang, Jiming and Schuler, Mary A and Friedman, Vikki and Mitchell-Olds, Thomas and Shippen, Dorothy E and dePamphilis, Claude W and Palmer, Jeffrey D and Freeling, Michael and Paterson, Andrew H and Gonsalves, Dennis and Wang, Lei and Alam, Maqsudul} } @article {38232, title = {Environmental signatures associated with cholera epidemics}, journal = {Proceedings of the National Academy of SciencesProceedings of the National Academy of Sciences}, volume = {105}, year = {2008}, type = {10.1073/pnas.0809654105}, abstract = {The causative agent of cholera, Vibrio cholerae, has been shown to be autochthonous to riverine, estuarine, and coastal waters along with its host, the copepod, a significant member of the zooplankton community. Temperature, salinity, rainfall and plankton have proven to be important factors in the ecology of V. cholerae, influencing the transmission of the disease in those regions of the world where the human population relies on untreated water as a source of drinking water. In this study, the pattern of cholera outbreaks during 1998{\textendash}2006 in Kolkata, India, and Matlab, Bangladesh, and the earth observation data were analyzed with the objective of developing a prediction model for cholera. Satellite sensors were used to measure chlorophyll a concentration (CHL) and sea surface temperature (SST). In addition, rainfall data were obtained from both satellite and in situ gauge measurements. From the analyses, a statistically significant relationship between the time series for cholera in Kolkata, India, and CHL and rainfall anomalies was determined. A statistically significant one month lag was observed between CHL anomaly and number of cholera cases in Matlab, Bangladesh. From the results of the study, it is concluded that ocean and climate patterns are useful predictors of cholera epidemics, with the dynamics of endemic cholera being related to climate and/or changes in the aquatic ecosystem. When the ecology of V. cholerae is considered in predictive models, a robust early warning system for cholera in endemic regions of the world can be developed for public health planning and decision making.ecology epidemiology microbiology remote sensing}, isbn = {0027-8424, 1091-6490}, author = {Constantin de Magny, G. and Murtugudde, R. and Sapiano, M. R. P. and Nizam, A. and Brown, C. W. and Busalacchi, A. J. and Yunus, M. and Nair, G. B. and Gil, A. I. and Lanata, C. F. and Rita R. Colwell} } @article {38233, title = {Environmental Vibrio spp., isolated in Mozambique, contain a polymorphic group of integrative conjugative elements and class 1 integrons}, journal = {FEMS Microbiology EcologyFEMS Microbiology Ecology}, volume = {64}, year = {2008}, type = {10.1111/j.1574-6941.2008.00455.x}, abstract = {Circulation of mobile genetic elements linked to drug resistance spread was studied in Vibrio strains isolated from surface urban water (river and sea) and shellfish samples in 2002{\textendash}2003 in Maputo, Mozambique. Class 1 integrons and integrating conjugative elements (ICE) were investigated by PCR and mating experiments in strains of major health interest: 10 Vibrio cholerae, six Vibrio parahaemolyticus, two Vibrio alginolyticus and one Vibrio fluvialis. Resistance to at least two antibiotics (predominantly β-lactams) was detected in all the strains, with additional resistances to sulfamethoxazole, spectinomycin, streptomycin and/or trimethoprim. Class 1 integrons contributed partially to the expression of drug resistance and were found in five isolates: four V. cholerae (blaP1 cassette, one strain also contained the dfrA15 cassette) and one V. alginolyticus (aadA2 cassette). ICEs, apparently devoid of resistance genes, were found in eight V. cholerae, three V. parahaemolyticus and one V. fluvialis isolates. A wide variability was observed by molecular characterization of ICEs. Five ICEs were included in the SXT/R391 family and seven ICEs were not classified. Our results indicate that the SXT/R391 family and related ICEs comprise a large class of polymorphic genetic elements widely circulating in environmental Vibrio strains in Africa, beside those evidently linked to drug resistance in clinical isolates.}, keywords = {ICE, integron, Mozambique, Vibrio}, isbn = {1574-6941}, author = {Taviani, Elisa and Ceccarelli, Daniela and Lazaro, Nivalda and Bani, Stefania and Cappuccinelli, Piero and Rita R. Colwell and Colombo, Mauro M.} } @article {38366, title = {Maternal depletion of CTCF reveals multiple functions during oocyte and preimplantation embryo development}, journal = {DevelopmentDevelopment}, volume = {135}, year = {2008}, publisher = {The Company of Biologists Limited}, author = {Wan, L. B. and Pan, H. and Sridhar Hannenhalli and Cheng, Y. and Ma, J. and Fedoriw, A. and Lobanenkov, V. and Latham, K. E. and Schultz, R. M. and Bartolomei, M. S.} } @article {38383, title = {The minimum information about a genome sequence (MIGS) specification}, journal = {Nature biotechnologyNature biotechnology}, volume = {26}, year = {2008}, note = {http://www.ncbi.nlm.nih.gov/pubmed/18464787?dopt=Abstract}, type = {10.1038/nbt1360}, abstract = {With the quantity of genomic data increasing at an exponential rate, it is imperative that these data be captured electronically, in a standard format. Standardization activities must proceed within the auspices of open-access and international working bodies. To tackle the issues surrounding the development of better descriptions of genomic investigations, we have formed the Genomic Standards Consortium (GSC). Here, we introduce the minimum information about a genome sequence (MIGS) specification with the intent of promoting participation in its development and discussing the resources that will be required to develop improved mechanisms of metadata capture and exchange. As part of its wider goals, the GSC also supports improving the {\textquoteright}transparency{\textquoteright} of the information contained in existing genomic databases.}, keywords = {Chromosome mapping, Databases, Factual, information dissemination, Information Storage and Retrieval, Information Theory, Internationality}, author = {Field, Dawn and Garrity, George and Gray, Tanya and Morrison, Norman and J. Selengut and Sterk, Peter and Tatusova, Tatiana and Thomson, Nicholas and Allen, Michael J. and Angiuoli, Samuel V. and Ashburner, Michael and Axelrod, Nelson and Baldauf, Sandra and Ballard, Stuart and Boore, Jeffrey and Cochrane, Guy and Cole, James and Dawyndt, Peter and De Vos, Paul and DePamphilis, Claude and Edwards, Robert and Faruque, Nadeem and Feldman, Robert and Gilbert, Jack and Gilna, Paul and Gl{\"o}ckner, Frank Oliver and Goldstein, Philip and Guralnick, Robert and Haft, Dan and Hancock, David and Hermjakob, Henning and Hertz-Fowler, Christiane and Hugenholtz, Phil and Joint, Ian and Kagan, Leonid and Kane, Matthew and Kennedy, Jessie and Kowalchuk, George and Kottmann, Renzo and Kolker, Eugene and Kravitz, Saul and Kyrpides, Nikos and Leebens-Mack, Jim and Lewis, Suzanna E. and Li, Kelvin and Lister, Allyson L. and Lord, Phillip and Maltsev, Natalia and Markowitz, Victor and Martiny, Jennifer and Methe, Barbara and Mizrachi, Ilene and Moxon, Richard and Nelson, Karen and Parkhill, Julian and Proctor, Lita and White, Owen and Sansone, Susanna-Assunta and Spiers, Andrew and Stevens, Robert and Swift, Paul and Taylor, Chris and Tateno, Yoshio and Tett, Adrian and Turner, Sarah and Ussery, David and Vaughan, Bob and Ward, Naomi and Whetzel, Trish and San Gil, Ingio and Wilson, Gareth and Wipat, Anil} } @article {38388, title = {A molecular footprint of limb loss: sequence variation of the autopodial identity gene Hoxa-13}, journal = {J Mol EvolJ Mol Evol}, volume = {67}, year = {2008}, type = {10.1007/s00239-008-9156-7}, abstract = {The homeobox gene Hoxa-13 codes for a transcription factor involved in multiple functions, including body axis and hand/foot development in tetrapods. In this study we investigate whether the loss of one function (e.g., limb loss in snakes) left a molecular footprint in exon 1 of Hoxa-13 that could be associated with the release of functional constraints caused by limb loss. Fragments of the Hoxa-13 exon 1 were sequenced from 13 species and analyzed, with additional published sequences of the same region, using relative rates and likelihood-ratio tests. Five amino acid sites in exon 1 of Hoxa-13 were detected as evolving under positive selection in the stem lineage of snakes. To further investigate whether there is an association between limb loss and sequence variation in Hoxa-13, we used the random forest method on an alignment that included shark, basal fish lineages, and "eu-tetrapods" such as mammals, turtle, alligator, and birds. The random forest method approaches the problem as one of classification, where we seek to predict the presence or absence of autopodium based on amino acid variation in Hoxa-13 sequences. Different alignments tested were associated with similar error rates (18.42\%). The random forest method suggested that phenotypic states (autopodium present and absent) can often be correctly predicted based on Hoxa-13 sequences. Basal, nontetrapod gnat-hostomes that never had an autopodium were consistently classified as limbless together with the snakes, while eu-tetrapods without any history of limb loss in their phylogeny were also consistently classified as having a limb. Misclassifications affected mostly lizards, which, as a group, have a history of limb loss and limb re-evolution, and the urodele and caecilian in our sample. We conclude that a molecular footprint can be detected in Hoxa-13 that is associated with the lack of an autopodium; groups with classification ambiguity (lizards) are characterized by a history of repeated limb loss and possible limb re-evolution.}, author = {Kohlsdorf, T. and Michael P. Cummings and Lynch, V. J. and Stopper, G. F. and Takahashi, K. and Wagner, G. P.} } @article {49643, title = {Schistosoma mansoni: Microarray analysis of gene expression induced by host sex.}, journal = {Exp Parasitol}, volume = {120}, year = {2008}, month = {2008 Dec}, pages = {357-63}, abstract = {

Schistosoma mansoni is a digenetic trematode and a human parasite responsible for high social and economic impact. Although some authors have studied the effect of host hormones on parasites, not much is known about the effects of host sex on gene expression in Schistosomes. In order to study gene transcripts associated with the host sex, we compared the gene expression profiles of both male and female unisexual adult S. mansoni parasites raised on either male or female hosts, using DNA microarrays. Our results show that host sex caused differential expression of at least 11 genes in female parasites and of 134 in male parasites. Of the differentially expressed genes in female worms, 10 were preferentially expressed in female worms from male mice, while of the 134 differentially expressed genes in male parasites, 79 (59\%) were preferentially expressed in worms from female mice. Further investigation of the role of each of those genes will help understand better their importance in the pathogenesis of Schistosomiasis.

}, keywords = {Animals, Biomphalaria, Female, Gene expression, Host-Parasite Interactions, Male, Mice, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, RNA, Helminth, Schistosoma mansoni, Schistosomiasis mansoni, Sex Factors}, issn = {1090-2449}, doi = {10.1016/j.exppara.2008.09.005}, author = {Waisberg, M and Lobo, F P and Cerqueira, G C and Passos, L K J and Carvalho, O S and El-Sayed, N M and Franco, G R} } @article {38499, title = {Sex and age dimorphism of myocardial gene expression in nonischemic human heart failure}, journal = {Circulation: Cardiovascular GeneticsCirculation: Cardiovascular Genetics}, volume = {1}, year = {2008}, publisher = {Am Heart Assoc}, author = {Fermin, D. R. and Barac, A. and Lee, S. and Polster, S. P. and Sridhar Hannenhalli and Bergemann, T. L. and Grindle, S. and Dyke, D. B. and Pagani, F. and Miller, L. W. and others,} } @article {38136, title = {Bio-STEER: A Semantic Web workflow tool for Grid computing in the life sciences}, journal = {Future Generation Comp SystFuture Generation Comp Syst}, volume = {23}, year = {2007}, type = {DOI 10.1016/j.future.2006.07.011}, abstract = {Life science research is becoming evermore computationally intensive. Hence, from a computational resource perspective, Grid computing provides a logical approach to meeting many of the computational needs of life science research. However, there are several barriers to the widespread use of Grid computing in life sciences. In this paper, we attempt to address one particular barrier: the difficulty of using Grid computing by life scientists. Life science research often involves connecting multiple applications together to form a workflow. This process of constructing a workflow is complex. When combined with the difficulty of using Grid services, composing a meaningful workflow using Grid services can present a challenge to life scientists. Our proposed solution is a Semantic Web-enabled computing environment, called Bio-STEER. In BioSTEER, bioinformatics Grid services are mapped to Semantic Web services, described in OWL-S. We also defined an ontology in OWL to model bioinformatics applications. A graphical user interface helps to construct a scientific workflow by showing a list of services that are semantically sound: that is, the output of one service is semantically compatible with the input of the connecting service. Bio-STEER can help users take full advantaue of Grid services through a user-friendly graphical user interface (GUI), which allows them to easily construct the workflows they need. (c) 2006 Elsevier B.V. All rights reserved.}, keywords = {client/server, distributed, ENVIRONMENTS, integrated, interface, management, semantics, services, systems, user, web-base, workflow}, author = {Lee, S. and Wang, T. D. and Hashmi, N. and Michael P. Cummings} } @article {38147, title = {Characterization of Ehp, a Secreted Complement Inhibitory Protein from Staphylococcus aureus}, journal = {Journal of Biological ChemistryJournal of Biological Chemistry}, volume = {282}, year = {2007}, type = {10.1074/jbc.M704247200}, abstract = {We report here the discovery and characterization of Ehp, a new secreted Staphylococcus aureus protein that potently inhibits the alternative complement activation pathway. Ehp was identified through a genomic scan as an uncharacterized secreted protein from S. aureus, and immunoblotting of conditioned S. aureus culture medium revealed that the Ehp protein was secreted at the highest levels during log-phase bacterial growth. The mature Ehp polypeptide is composed of 80 residues and is 44\% identical to the complement inhibitory domain of S. aureus Efb (extracellular fibrinogen-binding protein). We observed preferential binding by Ehp to native and hydrolyzed C3 relative to fully active C3b and found that Ehp formed a subnanomolar affinity complex with these various forms of C3 by binding to its thioester-containing C3d domain. Site-directed mutagenesis demonstrated that Arg75 and Asn82 are important in forming the Ehp{\textperiodcentered}C3d complex, but loss of these side chains did not completely disrupt Ehp/C3d binding. This suggested the presence of a second C3d-binding site in Ehp, which was mapped to the proximity of Ehp Asn63. Further molecular level details of the Ehp/C3d interaction were revealed by solving the 2.7-{\r A} crystal structure of an Ehp{\textperiodcentered}C3d complex in which the low affinity site had been mutationally inactivated. Ehp potently inhibited C3b deposition onto sensitized surfaces by the alternative complement activation pathway. This inhibition was directly related to Ehp/C3d binding and was more potent than that seen for Efb-C. An altered conformation in Ehp-bound C3 was detected by monoclonal antibody C3-9, which is specific for a neoantigen exposed in activated forms of C3. Our results suggest that increased inhibitory potency of Ehp relative to Efb-C is derived from the second C3-binding site in this new protein.}, author = {Hammel, Michal and Sfyroera, Georgia and Pyrpassopoulos, Serapion and Ricklin, Daniel and Ramyar, Kasra X. and M. Pop and Jin, Zhongmin and Lambris, John D. and Geisbrecht, Brian V.} } @article {38172, title = {COMPUTATIONAL BIOLOGY}, journal = {Nucleic acids researchNucleic Acids Research}, volume = {35}, year = {2007}, publisher = {Information Retrieval Ltd}, author = {Leparc, G. G. and Mitra, R. D. and Vardhanabhuti, S. and Wang, J. and Sridhar Hannenhalli and Smit, S. and Widmann, J. and Knight, R. and Wu, S. and Zhang, Y. and others,} } @article {38242, title = {Evolution of genes and genomes on the Drosophila phylogeny}, journal = {NatureNature}, volume = {450}, year = {2007}, note = {[szlig]}, type = {10.1038/nature06341}, abstract = {Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.}, isbn = {0028-0836}, author = {Clark, Andrew G. and Eisen, Michael B. and Smith, Douglas R. and Bergman, Casey M. and Oliver, Brian and Markow, Therese A. and Kaufman, Thomas C. and Kellis, Manolis and Gelbart, William and Iyer, Venky N. and Pollard, Daniel A. and Sackton, Timothy B. and Larracuente, Amanda M. and Singh, Nadia D. and Abad, Jose P. and Abt, Dawn N. and Adryan, Boris and Aguade, Montserrat and Akashi, Hiroshi and Anderson, Wyatt W. and Aquadro, Charles F. and Ardell, David H. and Arguello, Roman and Artieri, Carlo G. and Barbash, Daniel A. and Barker, Daniel and Barsanti, Paolo and Batterham, Phil and Batzoglou, Serafim and Begun, Dave and Bhutkar, Arjun and Blanco, Enrico and Bosak, Stephanie A. and Bradley, Robert K. and Brand, Adrianne D. and Brent, Michael R. and Brooks, Angela N. and Brown, Randall H. and Butlin, Roger K. and Caggese, Corrado and Calvi, Brian R. and Carvalho, A. Bernardo de and Caspi, Anat and Castrezana, Sergio and Celniker, Susan E. and Chang, Jean L. and Chapple, Charles and Chatterji, Sourav and Chinwalla, Asif and Civetta, Alberto and Clifton, Sandra W. and Comeron, Josep M. and Costello, James C. and Coyne, Jerry A. and Daub, Jennifer and David, Robert G. and Delcher, Arthur L. and Delehaunty, Kim and Do, Chuong B. and Ebling, Heather and Edwards, Kevin and Eickbush, Thomas and Evans, Jay D. and Filipski, Alan and Findei, and Sven and Freyhult, Eva and Fulton, Lucinda and Fulton, Robert and Garcia, Ana C. L. and Gardiner, Anastasia and Garfield, David A. and Garvin, Barry E. and Gibson, Greg and Gilbert, Don and Gnerre, Sante and Godfrey, Jennifer and Good, Robert and Gotea, Valer and Gravely, Brenton and Greenberg, Anthony J. and Griffiths-Jones, Sam and Gross, Samuel and Guigo, Roderic and Gustafson, Erik A. and Haerty, Wilfried and Hahn, Matthew W. and Halligan, Daniel L. and Halpern, Aaron L. and Halter, Gillian M. and Han, Mira V. and Heger, Andreas and Hillier, LaDeana and Hinrichs, Angie S. and Holmes, Ian and Hoskins, Roger A. and Hubisz, Melissa J. and Hultmark, Dan and Huntley, Melanie A. and Jaffe, David B. and Jagadeeshan, Santosh and Jeck, William R. and Johnson, Justin and Jones, Corbin D. and Jordan, William C. and Karpen, Gary H. and Kataoka, Eiko and Keightley, Peter D. and Kheradpour, Pouya and Kirkness, Ewen F. and Koerich, Leonardo B. and Kristiansen, Karsten and Kudrna, Dave and Kulathinal, Rob J. and Kumar, Sudhir and Kwok, Roberta and Lander, Eric and Langley, Charles H. and Lapoint, Richard and Lazzaro, Brian P. and Lee, So-Jeong and Levesque, Lisa and Li, Ruiqiang and Lin, Chiao-Feng and Lin, Michael F. and Lindblad-Toh, Kerstin and Llopart, Ana and Long, Manyuan and Low, Lloyd and Lozovsky, Elena and Lu, Jian and Luo, Meizhong and Machado, Carlos A. and Makalowski, Wojciech and Marzo, Mar and Matsuda, Muneo and Matzkin, Luciano and McAllister, Bryant and McBride, Carolyn S. and McKernan, Brendan and McKernan, Kevin and Mendez-Lago, Maria and Minx, Patrick and Mollenhauer, Michael U. and Montooth, Kristi and Stephen M. Mount and Mu, Xu and Myers, Eugene and Negre, Barbara and Newfeld, Stuart and Nielsen, Rasmus and Noor, Mohamed A. F. and O{\textquoteright}Grady, Patrick and Pachter, Lior and Papaceit, Montserrat and Parisi, Matthew J. and Parisi, Michael and Parts, Leopold and Pedersen, Jakob S. and Pesole, Graziano and Phillippy, Adam M. and Ponting, Chris P. and M. Pop and Porcelli, Damiano and Powell, Jeffrey R. and Prohaska, Sonja and Pruitt, Kim and Puig, Marta and Quesneville, Hadi and Ram, Kristipati Ravi and Rand, David and Rasmussen, Matthew D. and Reed, Laura K. and Reenan, Robert and Reily, Amy and Remington, Karin A. and Rieger, Tania T. and Ritchie, Michael G. and Robin, Charles and Rogers, Yu-Hui and Rohde, Claudia and Rozas, Julio and Rubenfield, Marc J. and Ruiz, Alfredo and Russo, Susan and Salzberg, Steven L. and Sanchez-Gracia, Alejandro and Saranga, David J. and Sato, Hajime and Schaeffer, Stephen W. and Schatz, Michael C. and Schlenke, Todd and Schwartz, Russell and Segarra, Carmen and Singh, Rama S. and Sirot, Laura and Sirota, Marina and Sisneros, Nicholas B. and Smith, Chris D. and Smith, Temple F. and Spieth, John and Stage, Deborah E. and Stark, Alexander and Stephan, Wolfgang and Strausberg, Robert L. and Strempel, Sebastian and Sturgill, David and Sutton, Granger and Sutton, Granger G. and Tao, Wei and Teichmann, Sarah and Tobari, Yoshiko N. and Tomimura, Yoshihiko and Tsolas, Jason M. and Valente, Vera L. S. and Venter, Eli and Venter, J. Craig and Vicario, Saverio and Vieira, Filipe G. and Vilella, Albert J. and Villasante, Alfredo and Walenz, Brian and Wang, Jun and Wasserman, Marvin and Watts, Thomas and Wilson, Derek and Wilson, Richard K. and Wing, Rod A. and Wolfner, Mariana F. and Wong, Alex and Wong, Gane Ka-Shu and Wu, Chung- I. and Wu, Gabriel and Yamamoto, Daisuke and Yang, Hsiao-Pei and Yang, Shiaw-Pyng and Yorke, James A. and Yoshida, Kiyohito and Zdobnov, Evgeny and Zhang, Peili and Zhang, Yu and Zimin, Aleksey V. and Baldwin, Jennifer and Abdouelleil, Amr and Abdulkadir, Jamal and Abebe, Adal and Abera, Brikti and Abreu, Justin and Acer, St Christophe and Aftuck, Lynne and Alexander, Allen and An, Peter and Anderson, Erica and Anderson, Scott and Arachi, Harindra and Azer, Marc and Bachantsang, Pasang and Barry, Andrew and Bayul, Tashi and Berlin, Aaron and Bessette, Daniel and Bloom, Toby and Blye, Jason and Boguslavskiy, Leonid and Bonnet, Claude and Boukhgalter, Boris and Bourzgui, Imane and Brown, Adam and Cahill, Patrick and Channer, Sheridon and Cheshatsang, Yama and Chuda, Lisa and Citroen, Mieke and Collymore, Alville and Cooke, Patrick and Costello, Maura and D{\textquoteright}Aco, Katie and Daza, Riza and Haan, Georgius De and DeGray, Stuart and DeMaso, Christina and Dhargay, Norbu and Dooley, Kimberly and Dooley, Erin and Doricent, Missole and Dorje, Passang and Dorjee, Kunsang and Dupes, Alan and Elong, Richard and Falk, Jill and Farina, Abderrahim and Faro, Susan and Ferguson, Diallo and Fisher, Sheila and Foley, Chelsea D. and Franke, Alicia and Friedrich, Dennis and Gadbois, Loryn and Gearin, Gary and Gearin, Christina R. and Giannoukos, Georgia and Goode, Tina and Graham, Joseph and Grandbois, Edward and Grewal, Sharleen and Gyaltsen, Kunsang and Hafez, Nabil and Hagos, Birhane and Hall, Jennifer and Henson, Charlotte and Hollinger, Andrew and Honan, Tracey and Huard, Monika D. and Hughes, Leanne and Hurhula, Brian and Husby, M. Erii and Kamat, Asha and Kanga, Ben and Kashin, Seva and Khazanovich, Dmitry and Kisner, Peter and Lance, Krista and Lara, Marcia and Lee, William and Lennon, Niall and Letendre, Frances and LeVine, Rosie and Lipovsky, Alex and Liu, Xiaohong and Liu, Jinlei and Liu, Shangtao and Lokyitsang, Tashi and Lokyitsang, Yeshi and Lubonja, Rakela and Lui, Annie and MacDonald, Pen and Magnisalis, Vasilia and Maru, Kebede and Matthews, Charles and McCusker, William and McDonough, Susan and Mehta, Teena and Meldrim, James and Meneus, Louis and Mihai, Oana and Mihalev, Atanas and Mihova, Tanya and Mittelman, Rachel and Mlenga, Valentine and Montmayeur, Anna and Mulrain, Leonidas and Navidi, Adam and Naylor, Jerome and Negash, Tamrat and Nguyen, Thu and Nguyen, Nga and Nicol, Robert and Norbu, Choe and Norbu, Nyima and Novod, Nathaniel and O{\textquoteright}Neill, Barry and Osman, Sahal and Markiewicz, Eva and Oyono, Otero L. and Patti, Christopher and Phunkhang, Pema and Pierre, Fritz and Priest, Margaret and Raghuraman, Sujaa and Rege, Filip and Reyes, Rebecca and Rise, Cecil and Rogov, Peter and Ross, Keenan and Ryan, Elizabeth and Settipalli, Sampath and Shea, Terry and Sherpa, Ngawang and Shi, Lu and Shih, Diana and Sparrow, Todd and Spaulding, Jessica and Stalker, John and Stange-Thomann, Nicole and Stavropoulos, Sharon and Stone, Catherine and Strader, Christopher and Tesfaye, Senait and Thomson, Talene and Thoulutsang, Yama and Thoulutsang, Dawa and Topham, Kerri and Topping, Ira and Tsamla, Tsamla and Vassiliev, Helen and Vo, Andy and Wangchuk, Tsering and Wangdi, Tsering and Weiand, Michael and Wilkinson, Jane and Wilson, Adam and Yadav, Shailendra and Young, Geneva and Yu, Qing and Zembek, Lisa and Zhong, Danni and Zimmer, Andrew and Zwirko, Zac and Jaffe, David B. and Alvarez, Pablo and Brockman, Will and Butler, Jonathan and Chin, CheeWhye and Gnerre, Sante and Grabherr, Manfred and Kleber, Michael and Mauceli, Evan and MacCallum, Iain} } @article {49677, title = {Evolution of genes and genomes on the Drosophila phylogeny.}, journal = {Nature}, volume = {450}, year = {2007}, month = {2007 Nov 8}, pages = {203-18}, abstract = {

Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

}, keywords = {Animals, Codon, DNA Transposable Elements, Drosophila, Drosophila Proteins, Evolution, Molecular, Gene Order, Genes, Insect, Genome, Insect, Genome, Mitochondrial, Genomics, Immunity, Multigene Family, Phylogeny, Reproduction, RNA, Untranslated, sequence alignment, Sequence Analysis, DNA, Synteny}, issn = {1476-4687}, doi = {10.1038/nature06341}, author = {Clark, Andrew G and Eisen, Michael B and Smith, Douglas R and Bergman, Casey M and Oliver, Brian and Markow, Therese A and Kaufman, Thomas C and Kellis, Manolis and Gelbart, William and Iyer, Venky N and Pollard, Daniel A and Sackton, Timothy B and Larracuente, Amanda M and Singh, Nadia D and Abad, Jose P and Abt, Dawn N and Adryan, Boris and Aguade, Montserrat and Akashi, Hiroshi and Anderson, Wyatt W and Aquadro, Charles F and Ardell, David H and Arguello, Roman and Artieri, Carlo G and Barbash, Daniel A and Barker, Daniel and Barsanti, Paolo and Batterham, Phil and Batzoglou, Serafim and Begun, Dave and Bhutkar, Arjun and Blanco, Enrico and Bosak, Stephanie A and Bradley, Robert K and Brand, Adrianne D and Brent, Michael R and Brooks, Angela N and Brown, Randall H and Butlin, Roger K and Caggese, Corrado and Calvi, Brian R and Bernardo de Carvalho, A and Caspi, Anat and Castrezana, Sergio and Celniker, Susan E and Chang, Jean L and Chapple, Charles and Chatterji, Sourav and Chinwalla, Asif and Civetta, Alberto and Clifton, Sandra W and Comeron, Josep M and Costello, James C and Coyne, Jerry A and Daub, Jennifer and David, Robert G and Delcher, Arthur L and Delehaunty, Kim and Do, Chuong B and Ebling, Heather and Edwards, Kevin and Eickbush, Thomas and Evans, Jay D and Filipski, Alan and Findeiss, Sven and Freyhult, Eva and Fulton, Lucinda and Fulton, Robert and Garcia, Ana C L and Gardiner, Anastasia and Garfield, David A and Garvin, Barry E and Gibson, Greg and Gilbert, Don and Gnerre, Sante and Godfrey, Jennifer and Good, Robert and Gotea, Valer and Gravely, Brenton and Greenberg, Anthony J and Griffiths-Jones, Sam and Gross, Samuel and Guigo, Roderic and Gustafson, Erik A and Haerty, Wilfried and Hahn, Matthew W and Halligan, Daniel L and Halpern, Aaron L and Halter, Gillian M and Han, Mira V and Heger, Andreas and Hillier, LaDeana and Hinrichs, Angie S and Holmes, Ian and Hoskins, Roger A and Hubisz, Melissa J and Hultmark, Dan and Huntley, Melanie A and Jaffe, David B and Jagadeeshan, Santosh and Jeck, William R and Johnson, Justin and Jones, Corbin D and Jordan, William C and Karpen, Gary H and Kataoka, Eiko and Keightley, Peter D and Kheradpour, Pouya and Kirkness, Ewen F and Koerich, Leonardo B and Kristiansen, Karsten and Kudrna, Dave and Kulathinal, Rob J and Kumar, Sudhir and Kwok, Roberta and Lander, Eric and Langley, Charles H and Lapoint, Richard and Lazzaro, Brian P and Lee, So-Jeong and Levesque, Lisa and Li, Ruiqiang and Lin, Chiao-Feng and Lin, Michael F and Lindblad-Toh, Kerstin and Llopart, Ana and Long, Manyuan and Low, Lloyd and Lozovsky, Elena and Lu, Jian and Luo, Meizhong and Machado, Carlos A and Makalowski, Wojciech and Marzo, Mar and Matsuda, Muneo and Matzkin, Luciano and McAllister, Bryant and McBride, Carolyn S and McKernan, Brendan and McKernan, Kevin and Mendez-Lago, Maria and Minx, Patrick and Mollenhauer, Michael U and Montooth, Kristi and Mount, Stephen M and Mu, Xu and Myers, Eugene and Negre, Barbara and Newfeld, Stuart and Nielsen, Rasmus and Noor, Mohamed A F and O{\textquoteright}Grady, Patrick and Pachter, Lior and Papaceit, Montserrat and Parisi, Matthew J and Parisi, Michael and Parts, Leopold and Pedersen, Jakob S and Pesole, Graziano and Phillippy, Adam M and Ponting, Chris P and Pop, Mihai and Porcelli, Damiano and Powell, Jeffrey R and Prohaska, Sonja and Pruitt, Kim and Puig, Marta and Quesneville, Hadi and Ram, Kristipati Ravi and Rand, David and Rasmussen, Matthew D and Reed, Laura K and Reenan, Robert and Reily, Amy and Remington, Karin A and Rieger, Tania T and Ritchie, Michael G and Robin, Charles and Rogers, Yu-Hui and Rohde, Claudia and Rozas, Julio and Rubenfield, Marc J and Ruiz, Alfredo and Russo, Susan and Salzberg, Steven L and Sanchez-Gracia, Alejandro and Saranga, David J and Sato, Hajime and Schaeffer, Stephen W and Schatz, Michael C and Schlenke, Todd and Schwartz, Russell and Segarra, Carmen and Singh, Rama S and Sirot, Laura and Sirota, Marina and Sisneros, Nicholas B and Smith, Chris D and Smith, Temple F and Spieth, John and Stage, Deborah E and Stark, Alexander and Stephan, Wolfgang and Strausberg, Robert L and Strempel, Sebastian and Sturgill, David and Sutton, Granger and Sutton, Granger G and Tao, Wei and Teichmann, Sarah and Tobari, Yoshiko N and Tomimura, Yoshihiko and Tsolas, Jason M and Valente, Vera L S and Venter, Eli and Venter, J Craig and Vicario, Saverio and Vieira, Filipe G and Vilella, Albert J and Villasante, Alfredo and Walenz, Brian and Wang, Jun and Wasserman, Marvin and Watts, Thomas and Wilson, Derek and Wilson, Richard K and Wing, Rod A and Wolfner, Mariana F and Wong, Alex and Wong, Gane Ka-Shu and Wu, Chung-I and Wu, Gabriel and Yamamoto, Daisuke and Yang, Hsiao-Pei and Yang, Shiaw-Pyng and Yorke, James A and Yoshida, Kiyohito and Zdobnov, Evgeny and Zhang, Peili and Zhang, Yu and Zimin, Aleksey V and Baldwin, Jennifer and Abdouelleil, Amr and Abdulkadir, Jamal and Abebe, Adal and Abera, Brikti and Abreu, Justin and Acer, St Christophe and Aftuck, Lynne and Alexander, Allen and An, Peter and Anderson, Erica and Anderson, Scott and Arachi, Harindra and Azer, Marc and Bachantsang, Pasang and Barry, Andrew and Bayul, Tashi and Berlin, Aaron and Bessette, Daniel and Bloom, Toby and Blye, Jason and Boguslavskiy, Leonid and Bonnet, Claude and Boukhgalter, Boris and Bourzgui, Imane and Brown, Adam and Cahill, Patrick and Channer, Sheridon and Cheshatsang, Yama and Chuda, Lisa and Citroen, Mieke and Collymore, Alville and Cooke, Patrick and Costello, Maura and D{\textquoteright}Aco, Katie and Daza, Riza and De Haan, Georgius and DeGray, Stuart and DeMaso, Christina and Dhargay, Norbu and Dooley, Kimberly and Dooley, Erin and Doricent, Missole and Dorje, Passang and Dorjee, Kunsang and Dupes, Alan and Elong, Richard and Falk, Jill and Farina, Abderrahim and Faro, Susan and Ferguson, Diallo and Fisher, Sheila and Foley, Chelsea D and Franke, Alicia and Friedrich, Dennis and Gadbois, Loryn and Gearin, Gary and Gearin, Christina R and Giannoukos, Georgia and Goode, Tina and Graham, Joseph and Grandbois, Edward and Grewal, Sharleen and Gyaltsen, Kunsang and Hafez, Nabil and Hagos, Birhane and Hall, Jennifer and Henson, Charlotte and Hollinger, Andrew and Honan, Tracey and Huard, Monika D and Hughes, Leanne and Hurhula, Brian and Husby, M Erii and Kamat, Asha and Kanga, Ben and Kashin, Seva and Khazanovich, Dmitry and Kisner, Peter and Lance, Krista and Lara, Marcia and Lee, William and Lennon, Niall and Letendre, Frances and LeVine, Rosie and Lipovsky, Alex and Liu, Xiaohong and Liu, Jinlei and Liu, Shangtao and Lokyitsang, Tashi and Lokyitsang, Yeshi and Lubonja, Rakela and Lui, Annie and MacDonald, Pen and Magnisalis, Vasilia and Maru, Kebede and Matthews, Charles and McCusker, William and McDonough, Susan and Mehta, Teena and Meldrim, James and Meneus, Louis and Mihai, Oana and Mihalev, Atanas and Mihova, Tanya and Mittelman, Rachel and Mlenga, Valentine and Montmayeur, Anna and Mulrain, Leonidas and Navidi, Adam and Naylor, Jerome and Negash, Tamrat and Nguyen, Thu and Nguyen, Nga and Nicol, Robert and Norbu, Choe and Norbu, Nyima and Novod, Nathaniel and O{\textquoteright}Neill, Barry and Osman, Sahal and Markiewicz, Eva and Oyono, Otero L and Patti, Christopher and Phunkhang, Pema and Pierre, Fritz and Priest, Margaret and Raghuraman, Sujaa and Rege, Filip and Reyes, Rebecca and Rise, Cecil and Rogov, Peter and Ross, Keenan and Ryan, Elizabeth and Settipalli, Sampath and Shea, Terry and Sherpa, Ngawang and Shi, Lu and Shih, Diana and Sparrow, Todd and Spaulding, Jessica and Stalker, John and Stange-Thomann, Nicole and Stavropoulos, Sharon and Stone, Catherine and Strader, Christopher and Tesfaye, Senait and Thomson, Talene and Thoulutsang, Yama and Thoulutsang, Dawa and Topham, Kerri and Topping, Ira and Tsamla, Tsamla and Vassiliev, Helen and Vo, Andy and Wangchuk, Tsering and Wangdi, Tsering and Weiand, Michael and Wilkinson, Jane and Wilson, Adam and Yadav, Shailendra and Young, Geneva and Yu, Qing and Zembek, Lisa and Zhong, Danni and Zimmer, Andrew and Zwirko, Zac and Jaffe, David B and Alvarez, Pablo and Brockman, Will and Butler, Jonathan and Chin, CheeWhye and Gnerre, Sante and Grabherr, Manfred and Kleber, Michael and Mauceli, Evan and MacCallum, Iain} } @article {38273, title = {GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo}, journal = {DevelopmentDevelopment}, volume = {134}, year = {2007}, type = {10.1242/dev.02720}, abstract = {In vitro studies have suggested that members of the GATA and Nkx transcription factor families physically interact, and synergistically activate pulmonary epithelial- and cardiac-gene promoters. However, the relevance of this synergy has not been demonstrated in vivo. We show that Gata6-Titf1 (Gata6-Nkx2.1) double heterozygous (G6-Nkx DH) embryos and mice have severe defects in pulmonary epithelial differentiation and distal airway development, as well as reduced phospholipid production. The defects in G6-Nkx DH embryos and mice are similar to those observed in human neonates with respiratory distress syndromes, including bronchopulmonary dysplasia, and differential gene expression analysis reveals essential developmental pathways requiring synergistic regulation by both Gata6 and Titf1 (Nkx2.1). These studies indicate that Gata6 and Nkx2.1 act in a synergistic manner to direct pulmonary epithelial differentiation and development in vivo, providing direct evidence that interactions between these two transcription factor families are crucial for the development of the tissues in which they are co-expressed.}, author = {Zhang, Yuzhen and Rath, Nibedita and Sridhar Hannenhalli and Wang, Zhishan and Cappola, Thomas and Kimura, Shioko and Atochina-Vasserman, Elena and Lu, Min Min and Beers, Michael F. and Morrisey, Edward E.} } @article {38377, title = {Microarray analysis of gene expression induced by sexual contact in Schistosoma mansoni}, journal = {BMC GenomicsBMC Genomics}, volume = {8}, year = {2007}, type = {10.1186/1471-2164-8-181}, abstract = {BACKGROUND:The parasitic trematode Schistosoma mansoni is one of the major causative agents of Schistosomiasis, a disease that affects approximately 200 million people, mostly in developing countries. Since much of the pathology is associated with eggs laid by the female worm, understanding the mechanisms involved in oogenesis and sexual maturation is an important step towards the discovery of new targets for effective drug therapy. It is known that the adult female worm only develops fully in the presence of a male worm and that the rates of oviposition and maturation of eggs are significantly increased by mating. In order to study gene transcripts associated with sexual maturation and oviposition, we compared the gene expression profiles of sexually mature and immature parasites using DNA microarrays.RESULTS:For each experiment, three amplified RNA microarray hybridizations and their dye swaps were analyzed. Our results show that 265 transcripts are differentially expressed in adult females and 53 in adult males when mature and immature worms are compared. Of the genes differentially expressed, 55\% are expressed at higher levels in paired females while the remaining 45\% are more expressed in unpaired ones and 56.6\% are expressed at higher levels in paired male worms while the remaining 43.4\% are more expressed in immature parasites. Real-time RT-PCR analysis validated the microarray results. Several new maturation associated transcripts were identified. Genes that were up-regulated in single-sex females were mostly related to energy generation (i.e. carbohydrate and protein metabolism, generation of precursor metabolites and energy, cellular catabolism, and organelle organization and biogenesis) while genes that were down-regulated related to RNA metabolism, reactive oxygen species metabolism, electron transport, organelle organization and biogenesis and protein biosynthesis.CONCLUSION:Our results confirm previous observations related to gene expression induced by sexual maturation in female schistosome worms. They also increase the list of S. mansoni maturation associated transcripts considerably, therefore opening new and exciting avenues for the study of the conjugal biology and development of new drugs against schistosomes.}, isbn = {1471-2164}, author = {Waisberg, Michael and Lobo, Francisco and Cerqueira, Gustavo and Passos, Liana and Carvalho, Omar and Franco, Gloria and Najib M. El-Sayed} } @article {49783, title = {New developments in the InterPro database.}, journal = {Nucleic Acids Res}, volume = {35}, year = {2007}, month = {2007 Jan}, pages = {D224-8}, abstract = {

InterPro is an integrated resource for protein families, domains and functional sites, which integrates the following protein signature databases: PROSITE, PRINTS, ProDom, Pfam, SMART, TIGRFAMs, PIRSF, SUPERFAMILY, Gene3D and PANTHER. The latter two new member databases have been integrated since the last publication in this journal. There have been several new developments in InterPro, including an additional reading field, new database links, extensions to the web interface and additional match XML files. InterPro has always provided matches to UniProtKB proteins on the website and in the match XML file on the FTP site. Additional matches to proteins in UniParc (UniProt archive) are now available for download in the new match XML files only. The latest InterPro release (13.0) contains more than 13 000 entries, covering over 78\% of all proteins in UniProtKB. The database is available for text- and sequence-based searches via a webserver (http://www.ebi.ac.uk/interpro), and for download by anonymous FTP (ftp://ftp.ebi.ac.uk/pub/databases/interpro). The InterProScan search tool is now also available via a web service at http://www.ebi.ac.uk/Tools/webservices/WSInterProScan.html.

}, keywords = {Databases, Protein, Internet, Protein Structure, Tertiary, Proteins, Sequence Analysis, Protein, Systems Integration, User-Computer Interface}, issn = {1362-4962}, doi = {10.1093/nar/gkl841}, author = {Mulder, Nicola J and Apweiler, Rolf and Attwood, Teresa K and Bairoch, Amos and Bateman, Alex and Binns, David and Bork, Peer and Buillard, Virginie and Cerutti, Lorenzo and Copley, Richard and Courcelle, Emmanuel and Das, Ujjwal and Daugherty, Louise and Dibley, Mark and Finn, Robert and Fleischmann, Wolfgang and Gough, Julian and Haft, Daniel and Hulo, Nicolas and Hunter, Sarah and Kahn, Daniel and Kanapin, Alexander and Kejariwal, Anish and Labarga, Alberto and Langendijk-Genevaux, Petra S and Lonsdale, David and Lopez, Rodrigo and Letunic, Ivica and Madera, Martin and Maslen, John and McAnulla, Craig and McDowall, Jennifer and Mistry, Jaina and Mitchell, Alex and Nikolskaya, Anastasia N and Orchard, Sandra and Orengo, Christine and Petryszak, Robert and Selengut, Jeremy D and Sigrist, Christian J A and Thomas, Paul D and Valentin, Franck and Wilson, Derek and Wu, Cathy H and Yeats, Corin} } @article {38405, title = {New Trypanosoma cruzi Repeated Element That Shows Site Specificity for Insertion}, journal = {Eukaryotic CellEukaryotic Cell}, volume = {6}, year = {2007}, type = {

10.1128/EC.00036-07

}, abstract = {A new family of site-specific repeated elements identified in Trypanosoma cruzi, which we named TcTREZO, is described here. TcTREZO appears to be a composite repeated element, since three subregions may be defined within it on the basis of sequence similarities with other T. cruzi sequences. Analysis of the distribution of TcTREZO in the genome clearly indicates that it displays site specificity for insertion. Most TcTREZO elements are flanked by conserved sequences. There is a highly conserved 68-bp sequence at the 5{\textquoteright} end of the element and a sequence domain of [~]500 bp without a well-defined borderline at the 3{\textquoteright} end. Northern blot hybridization and reverse transcriptase PCR analyses showed that TcTREZO transcripts are expressed as oligo(A)-terminated transcripts whose length corresponds to the unit size of the element (1.6 kb). Transcripts of [~]0.2 kb derived from a small part of TcTREZO are also detected in steady-state RNA. TcTREZO transcripts are unspliced and not translated. The copy number of TcTREZO sequences was estimated to be [~]173 copies per haploid genome. TcTREZO appears to have been assembled by insertions of sequences into a progenitor element. Once associated with each other, these subunits were amplified as a new transposable element. TcTREZO shows site specificity for insertion, suggesting that a sequence-specific endonuclease could be responsible for its insertion at a unique site.}, author = {Souza, Renata T. and Santos, Marcia R. M. and Lima, Fabio M. and Najib M. El-Sayed and Myler, Peter J. and Ruiz, Jeronimo C. and da Silveira, Jose Franco} } @article {38481, title = {Schistosoma mansoni genome: Closing in on a final gene set}, journal = {Experimental ParasitologyExperimental Parasitology}, volume = {117}, year = {2007}, type = {16/j.exppara.2007.06.005}, abstract = {The Schistosoma mansoni genome sequencing consortium has recently released the latest versions of the genome assembly as well as an automated preliminary gene structure annotation. The combined datasets constitute a vast resource for researchers to exploit in a variety of post-genomic studies with an emphasis of transcriptomic and proteomic tools. Here we present an innovative method used for combining diverse sources of evidence including ab initio gene predictions, protein and transcript sequence homologies, and cross-genome sequence homologies between S. mansoni and Schistosoma japonicum to define a comprehensive list of protein-coding genes.}, keywords = {Annotation, Gene finding, Genome, Schistosoma mansoni}, isbn = {0014-4894}, author = {Haas, Brian J. and Berriman, Matthew and Hirai, Hirohisa and Cerqueira, Gustavo G. and LoVerde, Philip T. and Najib M. El-Sayed} } @article {49681, title = {Spliceosomal small nuclear RNA genes in 11 insect genomes.}, journal = {RNA}, volume = {13}, year = {2007}, month = {2007 Jan}, pages = {5-14}, abstract = {

The removal of introns from the primary transcripts of protein-coding genes is accomplished by the spliceosome, a large macromolecular complex of which small nuclear RNAs (snRNAs) are crucial components. Following the recent sequencing of the honeybee (Apis mellifera) genome, we used various computational methods, ranging from sequence similarity search to RNA secondary structure prediction, to search for putative snRNA genes (including their promoters) and to examine their pattern of conservation among 11 available insect genomes (A. mellifera, Tribolium castaneum, Bombyx mori, Anopheles gambiae, Aedes aegypti, and six Drosophila species). We identified candidates for all nine spliceosomal snRNA genes in all the analyzed genomes. All the species contain a similar number of snRNA genes, with the exception of A. aegypti, whose genome contains more U1, U2, and U5 genes, and A. mellifera, whose genome contains fewer U2 and U5 genes. We found that snRNA genes are generally more closely related to homologs within the same genus than to those in other genera. Promoter regions for all spliceosomal snRNA genes within each insect species share similar sequence motifs that are likely to correspond to the PSEA (proximal sequence element A), the binding site for snRNA activating protein complex, but these promoter elements vary in sequence among the five insect families surveyed here. In contrast to the other insect species investigated, Dipteran genomes are characterized by a rapid evolution (or loss) of components of the U12 spliceosome and a striking loss of U12-type introns.

}, keywords = {Animals, Base Sequence, Bees, Computational Biology, Diptera, Evolution, Molecular, Genes, Insect, Genome, Insect, Molecular Sequence Data, Nucleic Acid Conformation, Phylogeny, Promoter Regions, Genetic, RNA Splicing, RNA, Small Nuclear, Sequence Analysis, RNA, Spliceosomes}, issn = {1355-8382}, doi = {10.1261/rna.259207}, author = {Mount, Stephen M and Gotea, Valer and Lin, Chiao-Feng and Hernandez, Kristina and Makalowski, Wojciech} } @article {38563, title = {Variola virus topoisomerase: DNA cleavage specificity and distribution of sites in Poxvirus genomes}, journal = {VirologyVirology}, volume = {365}, year = {2007}, type = {16/j.virol.2007.02.037}, abstract = {Topoisomerase enzymes regulate superhelical tension in DNA resulting from transcription, replication, repair, and other molecular transactions. Poxviruses encode an unusual type IB topoisomerase that acts only at conserved DNA sequences containing the core pentanucleotide 5{\textquoteright}-(T/C)CCTT-3{\textquoteright}. In X-ray structures of the variola virus topoisomerase bound to DNA, protein-DNA contacts were found to extend beyond the core pentanucleotide, indicating that the full recognition site has not yet been fully defined in functional studies. Here we report quantitation of DNA cleavage rates for an optimized 13~bp site and for all possible single base substitutions (40 total sites), with the goals of understanding the molecular mechanism of recognition and mapping topoisomerase sites in poxvirus genome sequences. The data allow a precise definition of enzyme-DNA interactions and the energetic contributions of each. We then used the resulting "action matrix" to show that favorable topoisomerase sites are distributed all along the length of poxvirus DNA sequences, consistent with a requirement for local release of superhelical tension in constrained topological domains. In orthopox genomes, an additional central cluster of sites was also evident. A negative correlation of predicted topoisomerase sites was seen relative to early terminators, but no correlation was seen with early or late promoters. These data define the full variola virus topoisomerase recognition site and provide a new window on topoisomerase function in vivo.}, keywords = {Annotation of topoisomerase sites, Sequence specific recognition, Topoisomerase IB, Variola virus}, isbn = {0042-6822}, author = {Minkah, Nana and Hwang, Young and Perry, Kay and Van Duyne, Gregory D. and Hendrickson, Robert and Lefkowitz, Elliot J. and Sridhar Hannenhalli and Bushman, Frederic D.} } @article {38159, title = {Comparative genomic evidence for a close relationship between the dimorphic prosthecate bacteria Hyphomonas neptunium and Caulobacter crescentus}, journal = {Journal of bacteriologyJournal of bacteriology}, volume = {188}, year = {2006}, note = {http://www.ncbi.nlm.nih.gov/pubmed/16980487?dopt=Abstract}, type = {10.1128/JB.00111-06}, abstract = {The dimorphic prosthecate bacteria (DPB) are alpha-proteobacteria that reproduce in an asymmetric manner rather than by binary fission and are of interest as simple models of development. Prior to this work, the only member of this group for which genome sequence was available was the model freshwater organism Caulobacter crescentus. Here we describe the genome sequence of Hyphomonas neptunium, a marine member of the DPB that differs from C. crescentus in that H. neptunium uses its stalk as a reproductive structure. Genome analysis indicates that this organism shares more genes with C. crescentus than it does with Silicibacter pomeroyi (a closer relative according to 16S rRNA phylogeny), that it relies upon a heterotrophic strategy utilizing a wide range of substrates, that its cell cycle is likely to be regulated in a similar manner to that of C. crescentus, and that the outer membrane complements of H. neptunium and C. crescentus are remarkably similar. H. neptunium swarmer cells are highly motile via a single polar flagellum. With the exception of cheY and cheR, genes required for chemotaxis were absent in the H. neptunium genome. Consistent with this observation, H. neptunium swarmer cells did not respond to any chemotactic stimuli that were tested, which suggests that H. neptunium motility is a random dispersal mechanism for swarmer cells rather than a stimulus-controlled navigation system for locating specific environments. In addition to providing insights into bacterial development, the H. neptunium genome will provide an important resource for the study of other interesting biological processes including chromosome segregation, polar growth, and cell aging.}, keywords = {Alphaproteobacteria, Bacterial Outer Membrane Proteins, Caulobacter crescentus, cell cycle, Chemotaxis, DNA, Bacterial, Flagella, Genome, Bacterial, Microbial Viability, Molecular Sequence Data, Movement, Sequence Analysis, DNA, Sequence Homology, signal transduction}, author = {Badger, Jonathan H. and Hoover, Timothy R. and Brun, Yves V. and Weiner, Ronald M. and Laub, Michael T. and Alexandre, Gladys and Mr{\'a}zek, Jan and Ren, Qinghu and Paulsen, Ian T. and Nelson, Karen E. and Khouri, Hoda M. and Radune, Diana and Sosa, Julia and Dodson, Robert J. and Sullivan, Steven A. and Rosovitz, M. J. and Madupu, Ramana and Brinkac, Lauren M. and Durkin, A. Scott and Daugherty, Sean C. and Kothari, Sagar P. and Giglio, Michelle Gwinn and Zhou, Liwei and Haft, Daniel H. and J. Selengut and Davidsen, Tanja M. and Yang, Qi and Zafar, Nikhat and Ward, Naomi L.} } @article {38161, title = {Comparative genomics of emerging human ehrlichiosis agents}, journal = {PLoS geneticsPLoS genetics}, volume = {2}, year = {2006}, note = {http://www.ncbi.nlm.nih.gov/pubmed/16482227?dopt=Abstract}, type = {10.1371/journal.pgen.0020021}, abstract = {Anaplasma (formerly Ehrlichia) phagocytophilum, Ehrlichia chaffeensis, and Neorickettsia (formerly Ehrlichia) sennetsu are intracellular vector-borne pathogens that cause human ehrlichiosis, an emerging infectious disease. We present the complete genome sequences of these organisms along with comparisons to other organisms in the Rickettsiales order. Ehrlichia spp. and Anaplasma spp. display a unique large expansion of immunodominant outer membrane proteins facilitating antigenic variation. All Rickettsiales have a diminished ability to synthesize amino acids compared to their closest free-living relatives. Unlike members of the Rickettsiaceae family, these pathogenic Anaplasmataceae are capable of making all major vitamins, cofactors, and nucleotides, which could confer a beneficial role in the invertebrate vector or the vertebrate host. Further analysis identified proteins potentially involved in vacuole confinement of the Anaplasmataceae, a life cycle involving a hematophagous vector, vertebrate pathogenesis, human pathogenesis, and lack of transovarial transmission. These discoveries provide significant insights into the biology of these obligate intracellular pathogens.}, keywords = {Animals, Biotin, DNA Repair, Ehrlichia, Ehrlichiosis, Genome, Genomics, HUMANS, Models, Biological, Phylogeny, Rickettsia, Ticks}, author = {Dunning Hotopp, Julie C. and Lin, Mingqun and Madupu, Ramana and Crabtree, Jonathan and Angiuoli, Samuel V. and Eisen, Jonathan A. and Eisen, Jonathan and Seshadri, Rekha and Ren, Qinghu and Wu, Martin and Utterback, Teresa R. and Smith, Shannon and Lewis, Matthew and Khouri, Hoda and Zhang, Chunbin and Niu, Hua and Lin, Quan and Ohashi, Norio and Zhi, Ning and Nelson, William and Brinkac, Lauren M. and Dodson, Robert J. and Rosovitz, M. J. and Sundaram, Jaideep and Daugherty, Sean C. and Davidsen, Tanja and Durkin, Anthony S. and Gwinn, Michelle and Haft, Daniel H. and J. Selengut and Sullivan, Steven A. and Zafar, Nikhat and Zhou, Liwei and Benahmed, Faiza and Forberger, Heather and Halpin, Rebecca and Mulligan, Stephanie and Robinson, Jeffrey and White, Owen and Rikihisa, Yasuko and Tettelin, Herv{\'e}} } @article {38243, title = {Evolution of non-LTR retrotransposons in the trypanosomatid genomes: Leishmania major has lost the active elements}, journal = {Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology}, volume = {145}, year = {2006}, type = {16/j.molbiopara.2005.09.017}, abstract = {The ingi and L1Tc non-LTR retrotransposons - which constitute the ingi clade - are abundant in the genome of the trypanosomatid species Trypanosoma brucei and Trypanosoma cruzi, respectively. The corresponding retroelements, however, are not present in the genome of a closely related trypanosomatid, Leishmania major. To study the evolution of non-LTR retrotransposons in trypanosomatids, we have analyzed all ingi/L1Tc elements and highly degenerate ingi/L1Tc-related sequences identified in the recently completed T. brucei, T. cruzi and L. major genomes. The coding sequences of 242 degenerate ingi/L1Tc-related elements (DIREs) in all three genomes were reconstituted by removing the numerous frame shifts. Three independent phylogenetic analyses conducted on the conserved domains encoded by these elements show that all DIREs, including the 52 L. major DIREs, form a monophyletic group belonging to the ingi clade. This indicates that the trypanosomatid ancestor contained active mobile elements that have been retained in the Trypanosoma species, but were lost from L. major genome, where only remnants (DIRE) are detectable. All 242 DIREs analyzed group together according to their species origin with the exception of 11 T. cruzi DIREs which are close to the T. brucei ingi/DIRE families. Considering the absence of known horizontal transfer between the African T. brucei and the South-American T. cruzi, this suggests that this group of elements evolved at a lower rate when compared to the other trypanosomatid elements. Interestingly, the only nucleotide sequence conserved between ingi and L1Tc (the first 79 residues) is also present at the 5{\textquoteright}-extremity of all the full length DIREs and suggests a possible role for this conserved motif, as well as for DIREs.}, keywords = {Degenerate retroelement, Evolution, Ingi, L1Tc, Leishmania major, Non-LTR retrotransposon, Retroposon, Trypanosoma brucei, Trypanosoma cruzi}, isbn = {0166-6851}, author = {Bringaud, Frederic and Ghedin, Elodie and Blandin, Ga{\"e}lle and Bartholomeu, Daniella C. and Caler, Elisabet and Levin, Mariano J. and Baltz, Th{\'e}o and Najib M. El-Sayed} } @article {38332, title = {Identification and cross-species comparison of canine osteoarthritic gene regulatory cis-elements}, journal = {Osteoarthritis and cartilage/OARS, Osteoarthritis Research SocietyOsteoarthritis and cartilage/OARS, Osteoarthritis Research Society}, volume = {14}, year = {2006}, author = {Sridhar Hannenhalli and Middleton, R. P. and Levy, S. and Perroud, B. and Holzwarth, J. A. and McDonald, K. and Hannah, S. S. and others,} } @article {38464, title = {Retroviral DNA integration: viral and cellular determinants of target-site selection}, journal = {PLoS pathogensPLoS pathogens}, volume = {2}, year = {2006}, publisher = {Public Library of Science}, author = {Lewinski, M. K. and Yamashita, M. and Emerman, M. and Ciuffi, A. and Marshall, H. and Crawford, G. and Collins, F. and Shinn, P. and Leipzig, J. and Sridhar Hannenhalli and others,} } @article {38479, title = {Schistosoma mansoni (Platyhelminthes, Trematoda) nuclear receptors: Sixteen new members and a novel subfamily}, journal = {GeneGene}, volume = {366}, year = {2006}, type = {16/j.gene.2005.09.013}, abstract = {Nuclear receptors (NRs) are important transcriptional modulators in metazoans. Sixteen new NRs were identified in the Platyhelminth trematode, Schistosoma mansoni. Three were found to possess novel tandem DNA-binding domains that identify a new subfamily of NR. Two NRs are homologues of the thyroid hormone receptor that previously were thought to be restricted to chordates. This study brings the total number of identified NR in S. mansoni to 21. Phylogenetic and comparative genomic analyses demonstrate that S. mansoni NRs share an evolutionary lineage with that of arthropods and vertebrates. Phylogenic analysis shows that more than half of the S. mansoni nuclear receptors evolved from a second gene duplication. As the second gene duplication of NRs was thought to be specific to vertebrates, our data challenge the current theory of NR evolution.}, keywords = {Nuclear receptors, Schistosoma mansoni}, isbn = {0378-1119}, author = {Wu, Wenjie and Niles, Edward G. and Najib M. El-Sayed and Berriman, Matthew and LoVerde, Philip T.} } @article {38486, title = {Selection of Target Sites for Mobile DNA Integration in the Human Genome}, journal = {PLoS Comput BiolPLoS Comput BiolPLoS Comput BiolPLoS Comput Biol}, volume = {2}, year = {2006}, type = {10.1371/journal.pcbi.0020157}, abstract = {DNA sequences from retroviruses, retrotransposons, DNA transposons, and parvoviruses can all become integrated into the human genome. Accumulation of such sequences accounts for at least 40\% of our genome today. These integrating elements are also of interest as gene-delivery vectors for human gene therapy. Here we present a comprehensive bioinformatic analysis of integration targeting by HIV, MLV, ASLV, SFV, L1, SB, and AAV. We used a mathematical method which allowed annotation of each base pair in the human genome for its likelihood of hosting an integration event by each type of element, taking advantage of more than 200 types of genomic annotation. This bioinformatic resource documents a wealth of new associations between genomic features and integration targeting. The study also revealed that the length of genomic intervals analyzed strongly affected the conclusions drawn{\textemdash}thus, answering the question {\textquotedblleft}What genomic features affect integration?{\textquotedblright} requires carefully specifying the length scale of interest.}, author = {Berry, Charles and Sridhar Hannenhalli and Leipzig, Jeremy and Bushman, Frederic D.} } @article {38131, title = {Bioinformatic Prediction of mRNA Targets of the Fragile X Mental Retardation Protein}, year = {2005}, author = {Simola, D. F. and Bucan, M. and Dalva, M. and Sridhar Hannenhalli and Liebhaber, S. and Ungar, L.} } @article {38188, title = {Critical Factors Influencing the Occurrence of Vibrio Cholerae in the Environment of Bangladesh}, journal = {Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol.}, volume = {71}, year = {2005}, type = {10.1128/AEM.71.8.4645-4654.2005}, abstract = {The occurrence of outbreaks of cholera in Africa in 1970 and in Latin America in 1991, mainly in coastal communities, and the appearance of the new serotype Vibrio cholerae O139 in India and subsequently in Bangladesh have stimulated efforts to understand environmental factors influencing the growth and geographic distribution of epidemic Vibrio cholerae serotypes. Because of the severity of recent epidemics, cholera is now being considered by some infectious disease investigators as a {\textquotedblleft}reemerging{\textquotedblright} disease, prompting new work on the ecology of vibrios. Epidemiological and ecological surveillance for cholera has been under way in four rural, geographically separated locations in Bangladesh for the past 4 years, during which both clinical and environmental samples were collected at biweekly intervals. The clinical epidemiology portion of the research has been published (Sack et al., J. Infect. Dis. 187:96-101, 2003). The results of environmental sampling and analysis of the environmental and clinical data have revealed significant correlations of water temperature, water depth, rainfall, conductivity, and copepod counts with the occurrence of cholera toxin-producing bacteria (presumably V. cholerae). The lag periods between increases or decreases in units of factors, such as temperature and salinity, and occurrence of cholera correlate with biological parameters, e.g., plankton population blooms. The new information on the ecology of V. cholerae is proving useful in developing environmental models for the prediction of cholera epidemics.}, isbn = {0099-2240, 1098-5336}, author = {Huq, Anwar and Sack, R. Bradley and Nizam, Azhar and Longini, Ira M. and Nair, G. Balakrish and Ali, Afsar and Morris, J. Glenn and Khan, M. N. Huda and Siddique, A. Kasem and Yunus, Mohammed and Albert, M. John and Sack, David A. and Rita R. Colwell} } @article {38292, title = {The genome of the African trypanosome Trypanosoma brucei}, journal = {ScienceScience}, volume = {309}, year = {2005}, author = {Berriman, M. and Ghedin, E. and Hertz-Fowler, C. and Blandin, G. and Renauld, H. and Bartholomeu, D. C. and Lennard, N. J. and Caler, E. and Hamlin, N. E. and Haas, B. and others,} } @article {38293, title = {The genome of the protist parasite Entamoeba histolytica}, journal = {NatureNature}, volume = {433}, year = {2005}, publisher = {Nature Publishing Group}, author = {Loftus, B. and Anderson, I. and Davies, R. and Alsmark, U. C. M. and Samuelson, J. and Amedeo, P. and Roncaglia, P. and Berriman, M. and Hirt, R. P. and Mann, B. J. and others,} } @article {38307, title = {Genome-Wide Analysis of Chromosomal Features Repressing Human Immunodeficiency Virus Transcription}, journal = {Journal of VirologyJ. Virol.Journal of VirologyJ. Virol.}, volume = {79}, year = {2005}, type = {10.1128/JVI.79.11.6610-6619.2005}, abstract = {We have investigated regulatory sequences in noncoding human DNA that are associated with repression of an integrated human immunodeficiency virus type 1 (HIV-1) promoter. HIV-1 integration results in the formation of precise and homogeneous junctions between viral and host DNA, but integration takes place at many locations. Thus, the variation in HIV-1 gene expression at different integration sites reports the activity of regulatory sequences at nearby chromosomal positions. Negative regulation of HIV transcription is of particular interest because of its association with maintaining HIV in a latent state in cells from infected patients. To identify chromosomal regulators of HIV transcription, we infected Jurkat T cells with an HIV-based vector transducing green fluorescent protein (GFP) and separated cells into populations containing well-expressed (GFP-positive) or poorly expressed (GFP-negative) proviruses. We then determined the chromosomal locations of the two classes by sequencing 971 junctions between viral and cellular DNA. Possible effects of endogenous cellular transcription were characterized by transcriptional profiling. Low-level GFP expression correlated with integration in (i) gene deserts, (ii) centromeric heterochromatin, and (iii) very highly expressed cellular genes. These data provide a genome-wide picture of chromosomal features that repress transcription and suggest models for transcriptional latency in cells from HIV-infected patients.}, isbn = {0022-538X, 1098-5514}, author = {Lewinski, M. K. and Bisgrove, D. and Shinn, P. and Chen, H. and Hoffmann, C. and Sridhar Hannenhalli and Verdin, E. and Berry, C. C. and Ecker, J. R. and Bushman, F. D.} } @article {38310, title = {Genome-wide analysis of retroviral DNA integration}, journal = {Nat Rev MicroNat Rev MicroNat Rev MicroNat Rev Micro}, volume = {3}, year = {2005}, type = {10.1038/nrmicro1263}, isbn = {1740-1526}, author = {Bushman, Frederic and Lewinski, Mary and Ciuffi, Angela and Barr, Stephen and Leipzig, Jeremy and Sridhar Hannenhalli and Hoffmann, Christian} } @article {38443, title = {Post-transcriptional Control in Mammalian Dendrites}, year = {2005}, author = {Simola, D. F. and Dalva, M. and Sridhar Hannenhalli and Liebhaber, S. and Bucan, M. and Ungar, L.} } @article {38450, title = {Promoter architecture and response to a positive regulator of archaeal transcription}, journal = {Molecular MicrobiologyMolecular Microbiology}, volume = {56}, year = {2005}, type = {10.1111/j.1365-2958.2005.04563.x}, abstract = {The archaeal transcription apparatus is chimeric: its core components (RNA polymerase and basal factors) closely resemble those of eukaryotic RNA polymerase II, but the putative archaeal transcriptional regulators are overwhelmingly of bacterial type. Particular interest attaches to how these bacterial-type effectors, especially activators, regulate a eukaryote-like transcription system. The hyperthermophilic archaeon Methanocaldococcus jannaschii encodes a potent transcriptional activator, Ptr2, related to the Lrp/AsnC family of bacterial regulators. Ptr2 activates rubredoxin 2 (rb2) transcription through a bipartite upstream activating site (UAS), and conveys its stimulatory effects on its cognate transcription machinery through direct recruitment of the TATA binding protein (TBP). A functional dissection of the highly constrained architecture of the rb2 promoter shows that a {\textquoteleft}one-site{\textquoteright} minimal UAS suffices for activation by Ptr2, and specifies the required placement of this site. The presence of such a simplified UAS upstream of the natural rubrerythrin (rbr) promoter also suffices for positive regulation by Ptr2 in vitro, and TBP recruitment remains the primary means of transcriptional activation at this promoter.}, isbn = {1365-2958}, author = {Ouhammouch, Mohamed and Langham, Geoffrey E. and Hausner, Winfried and Simpson, Anjana J. and Najib M. El-Sayed and Geiduschek, E. Peter} } @article {38525, title = {Temperature-Driven Campylobacter Seasonality in England and Wales}, journal = {Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol.}, volume = {71}, year = {2005}, type = {10.1128/AEM.71.1.85-92.2005}, abstract = {Campylobacter incidence in England and Wales between 1990 and 1999 was examined in conjunction with weather conditions. Over the 10-year interval, the average annual rate was determined to be 78.4 {\textpm} 15.0 cases per 100,000, with an upward trend. Rates were higher in males than in females, regardless of age, and highest in children less than 5 years old. Major regional differences were detected, with the highest rates in Wales and the southwest and the lowest in the southeast. The disease displayed a seasonal pattern, and increased campylobacter rates were found to be correlated with temperature. The most marked seasonal effect was observed for children under the age of 5. The seasonal pattern of campylobacter infections indicated a linkage with environmental factors rather than food sources. Therefore, public health interventions should not be restricted to food-borne approaches, and the epidemiology of the seasonal peak in human campylobacter infections may best be understood through studies in young children.}, isbn = {0099-2240, 1098-5336}, author = {Louis, Val{\'e}rie R. and Gillespie, Iain A. and O{\textquoteright}Brien, Sarah J. and Russek-Cohen, Estelle and Pearson, Andrew D. and Rita R. Colwell} } @article {49638, title = {What the genome sequence is revealing about trypanosome antigenic variation.}, journal = {Biochem Soc Trans}, volume = {33}, year = {2005}, month = {2005 Nov}, pages = {986-9}, abstract = {

African trypanosomes evade humoral immunity through antigenic variation, whereby they switch expression of the gene encoding their VSG (variant surface glycoprotein) coat. Switching proceeds by duplication of silent VSG genes into a transcriptionally active locus. The genome project has revealed that most of the silent archive consists of hundreds of subtelomeric VSG tandem arrays, and that most of these are not functional genes. Precedent suggests that they can contribute combinatorially to the formation of expressed, functional genes through segmental gene conversion. These findings from the genome project have major implications for evolution of the VSG archive and for transmission of the parasite in the field.

}, keywords = {Animals, Antigens, Protozoan, Evolution, Molecular, Genetic Variation, Genome, Trypanosomatina, Variant Surface Glycoproteins, Trypanosoma}, issn = {0300-5127}, doi = {10.1042/BST20050986}, author = {Barry, J D and Marcello, L and Morrison, L J and Read, A F and Lythgoe, K and Jones, N and Carrington, M and Blandin, G and B{\"o}hme, U and Caler, E and Hertz-Fowler, C and Renauld, H and El-Sayed, N and Berriman, M} } @article {38575, title = {Whole-genome sequence analysis of Pseudomonas syringae pv. phaseolicola 1448A reveals divergence among pathovars in genes involved in virulence and transposition}, journal = {Journal of bacteriologyJournal of bacteriology}, volume = {187}, year = {2005}, note = {http://www.ncbi.nlm.nih.gov/pubmed/16159782?dopt=Abstract}, type = {10.1128/JB.187.18.6488-6498.2005}, abstract = {Pseudomonas syringae pv. phaseolicola, a gram-negative bacterial plant pathogen, is the causal agent of halo blight of bean. In this study, we report on the genome sequence of P. syringae pv. phaseolicola isolate 1448A, which encodes 5,353 open reading frames (ORFs) on one circular chromosome (5,928,787 bp) and two plasmids (131,950 bp and 51,711 bp). Comparative analyses with a phylogenetically divergent pathovar, P. syringae pv. tomato DC3000, revealed a strong degree of conservation at the gene and genome levels. In total, 4,133 ORFs were identified as putative orthologs in these two pathovars using a reciprocal best-hit method, with 3,941 ORFs present in conserved, syntenic blocks. Although these two pathovars are highly similar at the physiological level, they have distinct host ranges; 1448A causes disease in beans, and DC3000 is pathogenic on tomato and Arabidopsis. Examination of the complement of ORFs encoding virulence, fitness, and survival factors revealed a substantial, but not complete, overlap between these two pathovars. Another distinguishing feature between the two pathovars is their distinctive sets of transposable elements. With access to a fifth complete pseudomonad genome sequence, we were able to identify 3,567 ORFs that likely comprise the core Pseudomonas genome and 365 ORFs that are P. syringae specific.}, keywords = {Bacterial Proteins, DNA, Bacterial, Genes, Bacterial, Genome, Bacterial, Molecular Sequence Data, Pseudomonas syringae, Species Specificity, virulence}, author = {Joardar, Vinita and Lindeberg, Magdalen and Jackson, Robert W. and J. Selengut and Dodson, Robert and Brinkac, Lauren M. and Daugherty, Sean C. and Deboy, Robert and Durkin, A. Scott and Giglio, Michelle Gwinn and Madupu, Ramana and Nelson, William C. and Rosovitz, M. J. and Sullivan, Steven and Crabtree, Jonathan and Creasy, Todd and Davidsen, Tanja and Haft, Dan H. and Zafar, Nikhat and Zhou, Liwei and Halpin, Rebecca and Holley, Tara and Khouri, Hoda and Feldblyum, Tamara and White, Owen and Fraser, Claire M. and Chatterjee, Arun K. and Cartinhour, Sam and Schneider, David J. and Mansfield, John and Collmer, Alan and Buell, C. Robin} } @proceedings {38100, title = {Abstracting workflows: unifying bioinformatics task conceptualization and specification through Semantic Web services}, year = {2004}, month = {2004}, address = {Cambridge, Massachusetts USA}, author = {Hashmi, N. and Lee, S. and Michael P. Cummings} } @article {38104, title = {Advances in schistosome genomics}, journal = {Trends in ParasitologyTrends in Parasitology}, volume = {20}, year = {2004}, type = {16/j.pt.2004.02.002}, abstract = {In Spring 2004, the first draft of the 270~Mb genome of Schistosoma mansoni will be released. This sequence is based on the assembly and annotation of a >7.5-fold coverage, shotgun sequencing project. The key stages involved in the international collaborative efforts that have led to the generation of these sequencing data for the parasite S. mansoni are discussed here.}, isbn = {1471-4922}, author = {Najib M. El-Sayed and Bartholomeu, Daniella and Ivens, Alasdair and Johnston, David A. and LoVerde, Philip T.} } @article {38149, title = {CHARACTERIZATION OF< i> Ath17, A QUANTITATIVE TRAIT LOCUS FOR ATHEROSCLEROSIS SUSCEPTIBILITY BETWEEN C57BL/6J AND 129S1/SvImJ; SINGLE-NUCLEOTIDE POLYMORPHISMS HAVE IMPORTANT IMPLICATIONS ON IDENTIFYING ATHEROSCLEROSIS MODIFIER GENES}, journal = {Cardiovascular PathologyCardiovascular Pathology}, volume = {13}, year = {2004}, publisher = {Elsevier}, author = {Ishimori, N. and Walsh, K. and Zheng, X. and Lu, F. and Sridhar Hannenhalli and Nusskern, D. and Mural, R. and Paigen, B.} } @article {49635, title = {Gene synteny and evolution of genome architecture in trypanosomatids.}, journal = {Mol Biochem Parasitol}, volume = {134}, year = {2004}, month = {2004 Apr}, pages = {183-91}, abstract = {

The trypanosomatid protozoa Trypanosoma brucei, Trypanosoma cruzi and Leishmania major are related human pathogens that cause markedly distinct diseases. Using information from genome sequencing projects currently underway, we have compared the sequences of large chromosomal fragments from each species. Despite high levels of divergence at the sequence level, these three species exhibit a striking conservation of gene order, suggesting that selection has maintained gene order among the trypanosomatids over hundreds of millions of years of evolution. The few sites of genome rearrangement between these species are marked by the presence of retrotransposon-like elements, suggesting that retrotransposons may have played an important role in shaping trypanosomatid genome organization. A degenerate retroelement was identified in L. major by examining the regions near breakage points of the synteny. This is the first such element found in L. major suggesting that retroelements were found in the common ancestor of all three species.

}, keywords = {Animals, Computational Biology, Evolution, Molecular, Gene Order, Genome, Protozoan, Genomics, Leishmania major, Multigene Family, Recombination, Genetic, Retroelements, Selection, Genetic, Synteny, Trypanosoma brucei brucei, Trypanosoma cruzi, Trypanosomatina}, issn = {0166-6851}, doi = {10.1016/j.molbiopara.2003.11.012}, author = {Ghedin, Elodie and Bringaud, Frederic and Peterson, Jeremy and Myler, Peter and Berriman, Matthew and Ivens, Alasdair and Andersson, Bj{\"o}rn and Bontempi, Esteban and Eisen, Jonathan and Angiuoli, Sam and Wanless, David and Von Arx, Anna and Murphy, Lee and Lennard, Nicola and Salzberg, Steven and Adams, Mark D and White, Owen and Hall, Neil and Stuart, Kenneth and Fraser, Claire M and el-Sayed, Najib M A} } @article {38302, title = {Genome sequence of Silicibacter pomeroyi reveals adaptations to the marine environment}, journal = {NatureNature}, volume = {432}, year = {2004}, note = {http://www.ncbi.nlm.nih.gov/pubmed/15602564?dopt=Abstract}, type = {10.1038/nature03170}, abstract = {Since the recognition of prokaryotes as essential components of the oceanic food web, bacterioplankton have been acknowledged as catalysts of most major biogeochemical processes in the sea. Studying heterotrophic bacterioplankton has been challenging, however, as most major clades have never been cultured or have only been grown to low densities in sea water. Here we describe the genome sequence of Silicibacter pomeroyi, a member of the marine Roseobacter clade (Fig. 1), the relatives of which comprise approximately 10-20\% of coastal and oceanic mixed-layer bacterioplankton. This first genome sequence from any major heterotrophic clade consists of a chromosome (4,109,442 base pairs) and megaplasmid (491,611 base pairs). Genome analysis indicates that this organism relies upon a lithoheterotrophic strategy that uses inorganic compounds (carbon monoxide and sulphide) to supplement heterotrophy. Silicibacter pomeroyi also has genes advantageous for associations with plankton and suspended particles, including genes for uptake of algal-derived compounds, use of metabolites from reducing microzones, rapid growth and cell-density-dependent regulation. This bacterium has a physiology distinct from that of marine oligotrophs, adding a new strategy to the recognized repertoire for coping with a nutrient-poor ocean.}, keywords = {Adaptation, Physiological, Carrier Proteins, Genes, Bacterial, Genome, Bacterial, marine biology, Molecular Sequence Data, Oceans and Seas, Phylogeny, plankton, RNA, Ribosomal, 16S, Roseobacter, Seawater}, author = {Moran, Mary Ann and Buchan, Alison and Gonz{\'a}lez, Jos{\'e} M. and Heidelberg, John F. and Whitman, William B. and Kiene, Ronald P. and Henriksen, James R. and King, Gary M. and Belas, Robert and Fuqua, Clay and Brinkac, Lauren and Lewis, Matt and Johri, Shivani and Weaver, Bruce and Pai, Grace and Eisen, Jonathan A. and Rahe, Elisha and Sheldon, Wade M. and Ye, Wenying and Miller, Todd R. and Carlton, Jane and Rasko, David A. and Paulsen, Ian T. and Ren, Qinghu and Daugherty, Sean C. and DeBoy, Robert T. and Dodson, Robert J. and Durkin, A. Scott and Madupu, Ramana and Nelson, William C. and Sullivan, Steven A. and Rosovitz, M. J. and Haft, Daniel H. and J. Selengut and Ward, Naomi} } @article {38410, title = {Occurrence and distribution of Vibrio cholerae in the coastal environment of Peru}, journal = {Environmental MicrobiologyEnvironmental Microbiology}, volume = {6}, year = {2004}, type = {10.1111/j.1462-2920.2004.00601.x}, abstract = {The occurrence and distribution of Vibrio cholerae in sea water and plankton along the coast of Peru were studied from October 1997 to June 2000, and included the 1997{\textendash}98 El Ni{\~n}o event. Samples were collected at four sites in coastal waters off Peru at monthly intervals. Of 178 samples collected and tested, V. cholerae O1 was cultured from 10 (5.6\%) samples, and V. cholerae O1 was detected by direct fluorescent antibody assay in 26 out of 159 samples tested (16.4\%). Based on the number of cholera cases reported in Peru from 1997 to 2000, a significant correlation was observed between cholera incidence and elevated sea surface temperature (SST) along the coast of Peru (P~<~0.001). From the results of this study, coastal sea water and zooplankton are concluded to be a reservoir for V. cholerae in Peru. The climate{\textendash}cholera relationship observed for the 1997{\textendash}98 El Ni{\~n}o year suggests that an early warning system for cholera risk can be established for Peru and neighbouring Latin American countries.}, isbn = {1462-2920}, author = {Gil, Ana I. and Louis, Val{\'e}rie R. and Rivera, Irma N. G. and Lipp, Erin and Huq, Anwar and Lanata, Claudio F. and Taylor, David N. and Russek-Cohen, Estelle and Choopun, Nipa and Sack, R. Bradley and Rita R. Colwell} } @article {38437, title = {Polylysogeny and prophage induction by secondary infection in Vibrio cholerae}, journal = {Environmental MicrobiologyEnvironmental Microbiology}, volume = {6}, year = {2004}, type = {10.1111/j.1462-2920.2004.00603.x}, abstract = {Strains of Vibrio cholerae O1, biotypes El Tor and classical, were infected with a known temperate phage (ΦP15) and monitored over a 15-day period for prophage induction. Over the course of the experiment two morphologically and three genomically distinct virus-like particles were observed from the phage-infected El Tor strain by transmission electron microscopy and field inversion gel electrophoresis, respectively, whereas only one phage, ΦP15, was observed from the infected classical strain. In the uninfected El Tor culture one prophage was spontaneously induced after 6~days. No induction in either strain was observed after treatment with mitomycin C. Data indicate that El Tor biotypes of V. cholerae may be polylysogenic and that secondary infection can promote multiple prophage induction. These traits may be important in the transfer of genetic material among V. cholerae by providing an environmentally relevant route for multiple prophage propagation and transmission.}, isbn = {1462-2920}, author = {Espeland, Eric M. and Lipp, Erin K. and Huq, Anwar and Rita R. Colwell} } @article {38480, title = {Schistosoma mansoni genome project: an update}, journal = {Parasitology InternationalParasitology International}, volume = {53}, year = {2004}, type = {16/j.parint.2004.01.009}, abstract = {A schistosome genome project was initiated by the World Health Organization in 1994 with the notion that the best prospects for identifying new targets for drugs, vaccines, and diagnostic development lie in schistosome gene discovery, development of chromosome maps, whole genome sequencing and genome analysis. Schistosoma mansoni has a haploid genome of 270 Mb contained on 8 pairs of chromosomes. It is estimated that the S. mansoni genome contains between 15~000 and 25~000 genes. There are approximately 16~689 ESTs obtained from diverse libraries representing different developmental stages of S. mansoni, deposited in the NCBI EST database. More than half of the deposited sequences correspond to genes of unknown function. Approximately 40-50\% of the sequences form unique clusters, suggesting that approximately 20-25\% of the total schistosome genes have been discovered. Efforts to develop low resolution chromosome maps are in progress. There is a genome sequencing program underway that will provide 3X sequence coverage of the S. mansoni genome that will result in approximately 95\% gene discovery. The genomics era has provided the resources to usher in the era of functional genomics that will involve microarrays to focus on specific metabolic pathways, proteomics to identify relevant proteins and protein-protein interactions to understand critical parasite pathways. Functional genomics is expected to accelerate the development of control and treatment strategies for schistosomiasis.}, keywords = {Chromosome mapping, Gene discovery, Genomics, Schistosoma mansoni}, isbn = {1383-5769}, author = {LoVerde, Philip T. and Hirai, Hirohisa and Merrick, Joseph M. and Lee, Norman H. and Najib M. El-Sayed} } @article {38574, title = {Whole genome comparisons of serotype 4b and 1/2a strains of the food-borne pathogen Listeria monocytogenes reveal new insights into the core genome components of this species}, journal = {Nucleic acids researchNucleic Acids Research}, volume = {32}, year = {2004}, note = {http://www.ncbi.nlm.nih.gov/pubmed/15115801?dopt=Abstract}, type = {10.1093/nar/gkh562}, abstract = {The genomes of three strains of Listeria monocytogenes that have been associated with food-borne illness in the USA were subjected to whole genome comparative analysis. A total of 51, 97 and 69 strain-specific genes were identified in L.monocytogenes strains F2365 (serotype 4b, cheese isolate), F6854 (serotype 1/2a, frankfurter isolate) and H7858 (serotype 4b, meat isolate), respectively. Eighty-three genes were restricted to serotype 1/2a and 51 to serotype 4b strains. These strain- and serotype-specific genes probably contribute to observed differences in pathogenicity, and the ability of the organisms to survive and grow in their respective environmental niches. The serotype 1/2a-specific genes include an operon that encodes the rhamnose biosynthetic pathway that is associated with teichoic acid biosynthesis, as well as operons for five glycosyl transferases and an adenine-specific DNA methyltransferase. A total of 8603 and 105 050 high quality single nucleotide polymorphisms (SNPs) were found on the draft genome sequences of strain H7858 and strain F6854, respectively, when compared with strain F2365. Whole genome comparative analyses revealed that the L.monocytogenes genomes are essentially syntenic, with the majority of genomic differences consisting of phage insertions, transposable elements and SNPs.}, keywords = {Base Composition, Chromosomes, Bacterial, DNA Transposable Elements, Food Microbiology, Genes, Bacterial, Genome, Bacterial, Genomics, Listeria monocytogenes, Meat, Open Reading Frames, Physical Chromosome Mapping, Polymorphism, Single Nucleotide, Prophages, Serotyping, Species Specificity, Synteny, virulence}, author = {Nelson, Karen E. and Fouts, Derrick E. and Mongodin, Emmanuel F. and Ravel, Jacques and DeBoy, Robert T. and Kolonay, James F. and Rasko, David A. and Angiuoli, Samuel V. and Gill, Steven R. and Paulsen, Ian T. and Peterson, Jeremy and White, Owen and Nelson, William C. and Nierman, William and Beanan, Maureen J. and Brinkac, Lauren M. and Daugherty, Sean C. and Dodson, Robert J. and Durkin, A. Scott and Madupu, Ramana and Haft, Daniel H. and J. Selengut and Van Aken, Susan and Khouri, Hoda and Fedorova, Nadia and Forberger, Heather and Tran, Bao and Kathariou, Sophia and Wonderling, Laura D. and Uhlich, Gaylen A. and Bayles, Darrell O. and Luchansky, John B. and Fraser, Claire M.} } @article {38576, title = {Whole-genome shotgun assembly and comparison of human genome assemblies}, journal = {Proceedings of the National Academy of Sciences of the United States of AmericaProceedings of the National Academy of Sciences of the United States of America}, volume = {101}, year = {2004}, publisher = {National Acad Sciences}, author = {Istrail, S. and Sutton, G. G. and Florea, L. and Halpern, A. L. and Mobarry, C. M. and Lippert, R. and Walenz, B. and Shatkay, H. and Dew, I. and Miller, J. R. and others,} } @article {38098, title = {A 4-Year Study of the Epidemiology of Vibrio Cholerae in Four Rural Areas of Bangladesh}, journal = {Journal of Infectious DiseasesJ Infect Dis.Journal of Infectious DiseasesJ Infect Dis.}, volume = {187}, year = {2003}, type = {10.1086/345865}, abstract = {How Vibrio cholerae spreads around the world and what determines its seasonal peaks in endemic areas are not known. These features of cholera have been hypothesized to be primarily the result of environmental factors associated with aquatic habitats that can now be identified. Since 1997, fortnightly surveillance in 4 widely separated geographic locations in Bangladesh has been performed to identify patients with cholera and to collect environmental data. A total of 5670 patients (53\% <5 years of age) have been studied; 14.3\% had cholera (10.4\% due to V. cholerae O1 El Tor, 3.8\% due to O139). Both serogroups were found in all locations; outbreaks were seasonal and often occurred simultaneously. Water-use patterns showed that bathing and washing clothes in tube-well water was significantly protective in two of the sites. These data will be correlated with environmental factors, to develop a model for prediction of cholera outbreaks}, isbn = {0022-1899, 1537-6613}, author = {Sack, R. Bradley and Siddique, A. Kasem and Longini, Ira M. and Nizam, Azhar and Yunus, Md and M. Sirajul Islam and Morris and Ali, Afsar and Huq, Anwar and Nair, G. Balakrish and Qadri, Firdausi and Faruque, Shah M. and Sack, David A. and Rita R. Colwell} } @article {38146, title = {Characterization of a Vibrio cholerae phage isolated from the coastal water of Peru}, journal = {Environmental MicrobiologyEnvironmental Microbiology}, volume = {5}, year = {2003}, type = {10.1046/j.1462-2920.2003.00411.x}, abstract = {A Vibrio cholerae bacteriophage, family Myoviridae, was isolated from seawater collected from the coastal water of Lima, Peru. Genome size was estimated to be 29~kbp. The temperate phage was specific to V. cholerae and infected 12/13 V. cholerae O1 strains and half of the four non-O1/non-O139 strains tested in this study. Vibrio cholerae O139 strains were resistant to infection and highest infection rates were obtained in low nutrient media amended with NaCl or prepared using seawater as diluent.}, isbn = {1462-2920}, author = {Talledo, Miguel and Rivera, Irma N. G. and Lipp, Erin K. and Neale, Angela and Karaolis, David and Huq, Anwar and Rita R. Colwell} } @article {38168, title = {The complete genome sequence of the Arabidopsis and tomato pathogen Pseudomonas syringae pv. tomato DC3000}, journal = {Proceedings of the National Academy of Sciences of the United States of AmericaProceedings of the National Academy of Sciences of the United States of America}, volume = {100}, year = {2003}, note = {http://www.ncbi.nlm.nih.gov/pubmed/12928499?dopt=Abstract}, type = {10.1073/pnas.1731982100}, abstract = {We report the complete genome sequence of the model bacterial pathogen Pseudomonas syringae pathovar tomato DC3000 (DC3000), which is pathogenic on tomato and Arabidopsis thaliana. The DC3000 genome (6.5 megabases) contains a circular chromosome and two plasmids, which collectively encode 5,763 ORFs. We identified 298 established and putative virulence genes, including several clusters of genes encoding 31 confirmed and 19 predicted type III secretion system effector proteins. Many of the virulence genes were members of paralogous families and also were proximal to mobile elements, which collectively comprise 7\% of the DC3000 genome. The bacterium possesses a large repertoire of transporters for the acquisition of nutrients, particularly sugars, as well as genes implicated in attachment to plant surfaces. Over 12\% of the genes are dedicated to regulation, which may reflect the need for rapid adaptation to the diverse environments encountered during epiphytic growth and pathogenesis. Comparative analyses confirmed a high degree of similarity with two sequenced pseudomonads, Pseudomonas putida and Pseudomonas aeruginosa, yet revealed 1,159 genes unique to DC3000, of which 811 lack a known function.}, keywords = {Arabidopsis, Base Sequence, Biological Transport, Genome, Bacterial, Lycopersicon esculentum, Molecular Sequence Data, Plant Growth Regulators, Plasmids, Pseudomonas, Reactive Oxygen Species, Siderophores, virulence}, author = {Buell, C. Robin and Joardar, Vinita and Lindeberg, Magdalen and J. Selengut and Paulsen, Ian T. and Gwinn, Michelle L. and Dodson, Robert J. and DeBoy, Robert T. and Durkin, A. Scott and Kolonay, James F. and Madupu, Ramana and Daugherty, Sean and Brinkac, Lauren and Beanan, Maureen J. and Haft, Daniel H. and Nelson, William C. and Davidsen, Tanja and Zafar, Nikhat and Zhou, Liwei and Liu, Jia and Yuan, Qiaoping and Khouri, Hoda and Fedorova, Nadia and Tran, Bao and Russell, Daniel and Berry, Kristi and Utterback, Teresa and Aken, Susan E. van and Feldblyum, Tamara V. and D{\textquoteright}Ascenzo, Mark and Deng, Wen-Ling and Ramos, Adela R. and Alfano, James R. and Cartinhour, Samuel and Chatterjee, Arun K. and Delaney, Terrence P. and Lazarowitz, Sondra G. and Martin, Gregory B. and Schneider, David J. and Tang, Xiaoyan and Bender, Carol L. and White, Owen and Fraser, Claire M. and Collmer, Alan} } @article {38206, title = {Direct Detection of Vibrio Cholerae and ctxA in Peruvian Coastal Water and Plankton by PCR}, journal = {Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol.}, volume = {69}, year = {2003}, type = {10.1128/AEM.69.6.3676-3680.2003}, abstract = {Seawater and plankton samples were collected over a period of 17 months from November 1998 to March 2000 along the coast of Peru. Total DNA was extracted from water and from plankton grouped by size into two fractions (64 μm to 202 μm and >202 μm). All samples were assayed for Vibrio cholerae, V. cholerae O1, V. cholerae O139, and ctxA by PCR. Of 50 samples collected and tested, 33 (66.0\%) were positive for V. cholerae in at least one of the three fractions. Of these, 62.5\% (n = 32) contained V. cholerae O1; ctxA was detected in 25\% (n = 20) of the V. cholerae O1-positive samples. None were positive for V. cholerae O139. Thus, PCR was successfully employed in detecting toxigenic V. cholerae directly in seawater and plankton samples and provides evidence for an environmental reservoir for this pathogen in Peruvian coastal waters.}, isbn = {0099-2240, 1098-5336}, author = {Lipp, Erin K. and Rivera, Irma N. G. and Gil, Ana I. and Espeland, Eric M. and Choopun, Nipa and Louis, Val{\'e}rie R. and Russek-Cohen, Estelle and Huq, Anwar and Rita R. Colwell} } @article {38214, title = {The dog genome: survey sequencing and comparative analysis}, journal = {ScienceScience}, volume = {301}, year = {2003}, publisher = {American Association for the Advancement of Science}, author = {Kirkness, E. F. and Bafna, V. and Halpern, A. L. and Levy, S. and Remington, K. and Rusch, D. B. and Delcher, A. L. and M. Pop and Wang, W. and Fraser, C. M. and others,} } @article {38291, title = {Genome of Geobacter sulfurreducens: metal reduction in subsurface environments}, journal = {Science (New York, N.Y.)Science (New York, N.Y.)}, volume = {302}, year = {2003}, note = {http://www.ncbi.nlm.nih.gov/pubmed/14671304?dopt=Abstract}, type = {10.1126/science.1088727}, abstract = {The complete genome sequence of Geobacter sulfurreducens, a delta-proteobacterium, reveals unsuspected capabilities, including evidence of aerobic metabolism, one-carbon and complex carbon metabolism, motility, and chemotactic behavior. These characteristics, coupled with the possession of many two-component sensors and many c-type cytochromes, reveal an ability to create alternative, redundant, electron transport networks and offer insights into the process of metal ion reduction in subsurface environments. As well as playing roles in the global cycling of metals and carbon, this organism clearly has the potential for use in bioremediation of radioactive metals and in the generation of electricity.}, keywords = {Acetates, Acetyl Coenzyme A, Aerobiosis, Anaerobiosis, Bacterial Proteins, Carbon, Chemotaxis, Chromosomes, Bacterial, Cytochromes c, Electron Transport, Energy Metabolism, Genes, Bacterial, Genes, Regulator, Genome, Bacterial, Geobacter, Hydrogen, Metals, Movement, Open Reading Frames, Oxidation-Reduction, Phylogeny}, author = {Meth{\'e}, B. A. and Nelson, K. E. and Eisen, J. A. and Paulsen, I. T. and Nelson, W. and Heidelberg, J. F. and Wu, D. and Wu, M. and Ward, N. and Beanan, M. J. and Dodson, R. J. and Madupu, R. and Brinkac, L. M. and Daugherty, S. C. and DeBoy, R. T. and Durkin, A. S. and Gwinn, M. and Kolonay, J. F. and Sullivan, S. A. and Haft, D. H. and J. Selengut and Davidsen, T. M. and Zafar, N. and White, O. and Tran, B. and Romero, C. and Forberger, H. A. and Weidman, J. and Khouri, H. and Feldblyum, T. V. and Utterback, T. R. and Van Aken, S. E. and Lovley, D. R. and Fraser, C. M.} } @article {38376, title = {Method of DNA extraction and application of multiplex polymerase chain reaction to detect toxigenic Vibrio cholerae O1 and O139 from aquatic ecosystems}, journal = {Environmental MicrobiologyEnvironmental Microbiology}, volume = {5}, year = {2003}, type = {10.1046/j.1462-2920.2003.00443.x}, abstract = {Vibrio cholerae is a free-living bacterium found in water and in association with plankton. V. cholerae non-O1/non-O139 strains are frequently isolated from aquatic ecosystems worldwide. Less frequently isolated are V. cholerae O1 and V. cholerae O139, the aetiological agents of cholera. These strains have two main virulence-associated factors, cholera toxin (CT) and toxin co-regulated pilus (TCP). By extracting total DNA from aquatic samples, the presence of pathogenic strains can be determined quickly and used to improve a microbiological risk assessment for cholera in coastal areas. Some methods suggested for DNA extraction from water samples are not applicable to all water types. We describe here a method for DNA extraction from coastal water and a multiplex polymerase chain reaction (PCR) for O1 and O139 serogroups. DNA extraction was successfully accomplished from 117 sea water samples collected from coastal areas of Per{\'u}, Brazil and the USA. DNA concentration in all samples varied from 20~ng to 480~{\textmu}g~{\textmu}l-1. The sensitivity of the DNA extraction method was 100 V. cholerae cells in 250~ml of water. The specificity of multiplex O1/O139 PCR was investigated by analysing 120 strains of V. cholerae, Vibrio and other Bacteria species. All V. cholerae O1 and O139 tested were positive. For cholera surveillance of aquatic environments and ballast water, total DNA extraction, followed by V. cholerae PCR, and O1/O139 serogroup and tcpA/ctxA genes by multiplex PCR offers an efficient system, permitting risk analysis for cholera in coastal areas.}, isbn = {1462-2920}, author = {Rivera, Irma N. G. and Lipp, Erin K. and Gil, Ana and Choopun, Nipa and Huq, Anwar and Rita R. Colwell} } @article {38429, title = {Persistence of adhesive properties in Vibrio cholerae after long-term exposure to sea water}, journal = {Environmental MicrobiologyEnvironmental Microbiology}, volume = {5}, year = {2003}, type = {10.1046/j.1462-2920.2003.00498.x}, abstract = {The effect of exposure to artificial sea water (ASW) on the ability of classical Vibrio cholerae O1 cells to interact with chitin-containing substrates and human intestinal cells was studied. Incubation of vibrios in ASW at 5{\textdegree}C and 18{\textdegree}C resulted in two kinds of cell responses: the viable but non-culturable (VBNC) state (i.e.~<0.1 colony forming unit ml-1) at 5{\textdegree}C, and starvation (i.e. maintenance of culturability of the population) at 18{\textdegree}C. The latter remained rod shaped and, after 40~days{\textquoteright} incubation, presented a 47{\textendash}58\% reduction in the number of cells attached to chitin, a 48{\textendash}53\% reduction in the number of bacteria adhering to copepods, and a 48{\textendash}54\% reduction in the number of bacteria adhering to human cultured intestinal cells, compared to control cells not suspended in ASW. Bacteria suspended in ASW at 5{\textdegree}C became coccoid and, after 40~days, showed 34{\textendash}42\% fewer cells attached to chitin, 52{\textendash}55\% fewer adhering to copep-ods, and 45{\textendash}48\% fewer cells adhering to intestinal cell monolayers, compared to controls. Sarkosyl-insoluble membrane proteins that bind chitin particles were isolated and analysed by SDS-PAGE. After 40~days incubation in ASW at both 5{\textdegree}C and 18{\textdegree}C vibrios expressed chitin-binding ligands similar to bacteria harvested in the stationary growth phase. It is concluded that as vibrios do not lose adhesive properties after long-term exposure to ASW, it is important to include methods for VBNC bacteria when testing environmental and clinical samples for purposes of public health safety.}, isbn = {1462-2920}, author = {Pruzzo, Carla and Tarsi, Renato and Del Mar Lle{\`o}, Maria and Signoretto, Caterina and Zampini, Massimiliano and Pane, Luigi and Rita R. Colwell and Canepari, Pietro} } @article {38445, title = {Predictability of Vibrio Cholerae in Chesapeake Bay}, journal = {Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol.}, volume = {69}, year = {2003}, type = {10.1128/AEM.69.5.2773-2785.2003}, abstract = {Vibrio cholerae is autochthonous to natural waters and can pose a health risk when it is consumed via untreated water or contaminated shellfish. The correlation between the occurrence of V. cholerae in Chesapeake Bay and environmental factors was investigated over a 3-year period. Water and plankton samples were collected monthly from five shore sampling sites in northern Chesapeake Bay (January 1998 to February 2000) and from research cruise stations on a north-south transect (summers of 1999 and 2000). Enrichment was used to detect culturable V. cholerae, and 21.1\% (n = 427) of the samples were positive. As determined by serology tests, the isolates, did not belong to serogroup O1 or O139 associated with cholera epidemics. A direct fluorescent-antibody assay was used to detect V. cholerae O1, and 23.8\% (n = 412) of the samples were positive. V. cholerae was more frequently detected during the warmer months and in northern Chesapeake Bay, where the salinity is lower. Statistical models successfully predicted the presence of V. cholerae as a function of water temperature and salinity. Temperatures above 19{\textdegree}C and salinities between 2 and 14 ppt yielded at least a fourfold increase in the number of detectable V. cholerae. The results suggest that salinity variation in Chesapeake Bay or other parameters associated with Susquehanna River inflow contribute to the variability in the occurrence of V. cholerae and that salinity is a useful indicator. Under scenarios of global climate change, increased climate variability, accompanied by higher stream flow rates and warmer temperatures, could favor conditions that increase the occurrence of V. cholerae in Chesapeake Bay.}, isbn = {0099-2240, 1098-5336}, author = {Louis, Val{\'e}rie R. and Russek-Cohen, Estelle and Choopun, Nipa and Rivera, Irma N. G. and Gangle, Brian and Jiang, Sunny C. and Rubin, Andrea and Patz, Jonathan A. and Huq, Anwar and Rita R. Colwell} } @article {38489, title = {The sequence and analysis of Trypanosoma brucei chromosome II}, journal = {Nucleic acids researchNucleic Acids Research}, volume = {31}, year = {2003}, author = {Najib M. El-Sayed and Ghedin, E. and Song, J. and MacLeod, A. and Bringaud, F. and Larkin, C. and Wanless, D. and Peterson, J. and Hou, L. and Taylor, S. and others,} } @article {49633, title = {The sequence and analysis of Trypanosoma brucei chromosome II.}, journal = {Nucleic Acids Res}, volume = {31}, year = {2003}, month = {2003 Aug 15}, pages = {4856-63}, abstract = {

We report here the sequence of chromosome II from Trypanosoma brucei, the causative agent of African sleeping sickness. The 1.2-Mb pairs encode about 470 predicted genes organised in 17 directional clusters on either strand, the largest cluster of which has 92 genes lined up over a 284-kb region. An analysis of the GC skew reveals strand compositional asymmetries that coincide with the distribution of protein-coding genes, suggesting these asymmetries may be the result of transcription-coupled repair on coding versus non-coding strand. A 5-cM genetic map of the chromosome reveals recombinational {\textquoteright}hot{\textquoteright} and {\textquoteright}cold{\textquoteright} regions, the latter of which is predicted to include the putative centromere. One end of the chromosome consists of a 250-kb region almost exclusively composed of RHS (pseudo)genes that belong to a newly characterised multigene family containing a hot spot of insertion for retroelements. Interspersed with the RHS genes are a few copies of truncated RNA polymerase pseudogenes as well as expression site associated (pseudo)genes (ESAGs) 3 and 4, and 76 bp repeats. These features are reminiscent of a vestigial variant surface glycoprotein (VSG) gene expression site. The other end of the chromosome contains a 30-kb array of VSG genes, the majority of which are pseudogenes, suggesting that this region may be a site for modular de novo construction of VSG gene diversity during transposition/gene conversion events.

}, keywords = {Animals, Antigens, Protozoan, Chromosome mapping, Chromosomes, DNA, Protozoan, Gene Duplication, Genes, Protozoan, Molecular Sequence Data, Pseudogenes, Recombination, Genetic, Sequence Analysis, DNA, Trypanosoma brucei brucei}, issn = {1362-4962}, author = {el-Sayed, Najib M A and Ghedin, Elodie and Song, Jinming and MacLeod, Annette and Bringaud, Frederic and Larkin, Christopher and Wanless, David and Peterson, Jeremy and Hou, Lihua and Taylor, Sonya and Tweedie, Alison and Biteau, Nicolas and Khalak, Hanif G and Lin, Xiaoying and Mason, Tanya and Hannick, Linda and Caler, Elisabet and Blandin, Ga{\"e}lle and Bartholomeu, Daniella and Simpson, Anjana J and Kaul, Samir and Zhao, Hong and Pai, Grace and Van Aken, Susan and Utterback, Teresa and Haas, Brian and Koo, Hean L and Umayam, Lowell and Suh, Bernard and Gerrard, Caroline and Leech, Vanessa and Qi, Rong and Zhou, Shiguo and Schwartz, David and Feldblyum, Tamara and Salzberg, Steven and Tait, Andrew and Turner, C Michael R and Ullu, Elisabetta and White, Owen and Melville, Sara and Adams, Mark D and Fraser, Claire M and Donelson, John E} } @article {38536, title = {The transcription factor Eyes absent is a protein tyrosine phosphatase}, journal = {NatureNature}, volume = {426}, year = {2003}, note = {http://www.ncbi.nlm.nih.gov/pubmed/14628053?dopt=Abstract}, type = {10.1038/nature02097}, abstract = {Post-translational modifications provide sensitive and flexible mechanisms to dynamically modulate protein function in response to specific signalling inputs. In the case of transcription factors, changes in phosphorylation state can influence protein stability, conformation, subcellular localization, cofactor interactions, transactivation potential and transcriptional output. Here we show that the evolutionarily conserved transcription factor Eyes absent (Eya) belongs to the phosphatase subgroup of the haloacid dehalogenase (HAD) superfamily, and propose a function for it as a non-thiol-based protein tyrosine phosphatase. Experiments performed in cultured Drosophila cells and in vitro indicate that Eyes absent has intrinsic protein tyrosine phosphatase activity and can autocatalytically dephosphorylate itself. Confirming the biological significance of this function, mutations that disrupt the phosphatase active site severely compromise the ability of Eyes absent to promote eye specification and development in Drosophila. Given the functional importance of phosphorylation-dependent modulation of transcription factor activity, this evidence for a nuclear transcriptional coactivator with intrinsic phosphatase activity suggests an unanticipated method of fine-tuning transcriptional regulation.}, keywords = {Amino Acid Motifs, Amino Acid Sequence, Animals, Antibodies, Phospho-Specific, Drosophila melanogaster, Drosophila Proteins, Embryonic Induction, eye, Eye Proteins, Gene Expression Regulation, Kinetics, Mice, Models, Molecular, Molecular Sequence Data, Mutation, Phosphorylation, Protein Conformation, Protein Tyrosine Phosphatases, Substrate Specificity, Transcription Factors}, author = {Tootle, Tina L. and Silver, Serena J. and Davies, Erin L. and Newman, Victoria and Latek, Robert R. and Mills, Ishara A. and J. Selengut and Parlikar, Beth E. W. and Rebay, Ilaria} } @article {38539, title = {Transcriptional regulation of protein complexes and biological pathways}, journal = {Mammalian GenomeMammalian Genome}, volume = {14}, year = {2003}, abstract = {The cis-element profile (or cis-profile) of a gene refers to the collection of transcription factor binding sites (TFBS) regulating the transcription of the gene. Underlying the various published studies that attempt to discover cis-elements in the vicinity of co-expressed genes via pattern detection algorithms, there is an implicit assumption that a correlation exists between co-expressed genes and their cis-profiles. In this study, we show that the cis-similarity, defined as the proportion of shared TFBS between two cis-element profiles, is higher for functionally linked interacting proteins as well as for members of a signal transduction pathway. A similar analysis of the enzymes catalyzing the conversion of adjacent substrates to products in a collection of metabolic pathways, did not reveal higher cis-similarity. The analysis is based on three distinct sources of publicly available data, namely, 1) the BIND database of interacting proteins, 2) known interactions in NMDAR protein complex, 3) the apoptosis pathway and nine pathways related to metabolism of cofactors and vitamins all from KEGG. Additionally, we analyze the cis-element profiles of all the genes in the glutamate receptor (GR) sub-complex of NMDAR complex to detect a set of cis-elements that occur adjacent to a majority of the genes. We show that most of the corresponding transcription factors are known to be involved in GR regulation by comparing our findings with the published biomedical literature. In addition, we were able to detect transcripts whose gene products associate with GR by searching for transcripts that share the same regulatory signals as those detected for GR. This suggests a novel computational methodology for constructing high-order gene regulatory models and detecting co-regulated gene products.}, isbn = {0938-8990}, author = {Sridhar Hannenhalli and Levy, Samuel} } @inbook {38153, title = {Combinatorial Algorithms for Design of DNA Arrays}, booktitle = {Chip TechnologyChip Technology}, series = {Advances in Biochemical Engineering/Biotechnology}, volume = {77}, year = {2002}, publisher = {Springer Berlin / Heidelberg}, organization = {Springer Berlin / Heidelberg}, abstract = {Optimal design of DNA arrays requires the development of algorithms with two-fold goals: reducing the effects caused by unintended illumination ( border length minimization problem ) and reducing the complexity of masks ( mask decomposition problem ). We describe algorithms that reduce the number of rectangles in mask decomposition by 20{\textendash}30\% as compared to a standard array design under the assumption that the arrangement of oligonucleotides on the array is fixed. This algorithm produces provably optimal solution for all studied real instances of array design. We also address the difficult problem of finding an arrangement which minimizes the border length and come up with a new idea of threading that significantly reduces the border length as compared to standard designs.}, isbn = {978-3-540-43215-9}, author = {Sridhar Hannenhalli and Hubbell, Earl and Lipshutz, Robert and Pevzner, Pavel}, editor = {Hoheisel, J{\"o}rg and Brazma, A. and B{\"u}ssow, K. and Cantor, C. and Christians, F. and Chui, G. and Diaz, R. and Drmanac, R. and Drmanac, S. and Eickhoff, H. and Fellenberg, K. and Sridhar Hannenhalli and Hoheisel, J. and Hou, A. and Hubbell, E. and Jin, H. and Jin, P. and Jurinke, C. and Konthur, Z. and K{\"o}ster, H. and Kwon, S. and Lacy, S. and Lehrach, H. and Lipshutz, R. and Little, D. and Lueking, A. and McGall, G. and Moeur, B. and Nordhoff, E. and Nyarsik, L. and Pevzner, P. and Robinson, A. and Sarkans, U. and Shafto, J. and Sohail, M. and Southern, E. and Swanson, D. and Ukrainczyk, T. and van den Boom, D. and Vilo, J. and Vingron, M. and Walter, G. and Xu, C.} } @article {38197, title = {Detection of Cytotoxin-Hemolysin mRNA in Nonculturable Populations of Environmental and Clinical Vibrio Vulnificus Strains in Artificial Seawater}, journal = {Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol.}, volume = {68}, year = {2002}, type = {10.1128/AEM.68.11.5641-5646.2002}, abstract = {The objective of this study was to develop a molecular detection method that better estimates the potential risk associated with the presence of Vibrio vulnificus. For that purpose, we applied seminested reverse transcription-PCR (RT-PCR) to viable but nonculturable (VBNC) populations of V. vulnificus and targeted the cytotoxin-hemolysin virulence gene vvhA. Three strains, two environmental, IF Vv10 and IF Vv18, and one clinical, C7184, were used in this study. Artificial seawater, inoculated with mid-log-phase cells, was maintained at 4{\textdegree}C. VBNC cells resulted after 3, 6, and 14 days for C7184, IF Vv18, and IF Vv10, respectively. Our data indicate that seminested RT-PCR is sensitive for the detection of vvhA mRNA in artificial seawater when exclusively nonculturable bacteria are present. This is the first report of the expression of a toxin gene in VBNC V. vulnificus. Moreover, vvhA transcripts were shown to persist in nonculturable populations over a 4.5-month period, with a progressive decline of the signal over time. This result indicates that special attention should be given to the presence of potentially pathogenic VBNC cells in environmental samples when assessing public health risk.}, isbn = {0099-2240, 1098-5336}, author = {Fischer-Le Saux, Marion and Hervio-Heath, Dominique and Loaec, Solen and Rita R. Colwell and Pommepuy, Monique} } @article {49687, title = {The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins.}, journal = {Science}, volume = {298}, year = {2002}, month = {2002 Dec 13}, pages = {2157-67}, abstract = {

The first chordates appear in the fossil record at the time of the Cambrian explosion, nearly 550 million years ago. The modern ascidian tadpole represents a plausible approximation to these ancestral chordates. To illuminate the origins of chordate and vertebrates, we generated a draft of the protein-coding portion of the genome of the most studied ascidian, Ciona intestinalis. The Ciona genome contains approximately 16,000 protein-coding genes, similar to the number in other invertebrates, but only half that found in vertebrates. Vertebrate gene families are typically found in simplified form in Ciona, suggesting that ascidians contain the basic ancestral complement of genes involved in cell signaling and development. The ascidian genome has also acquired a number of lineage-specific innovations, including a group of genes engaged in cellulose metabolism that are related to those in bacteria and fungi.

}, keywords = {Alleles, Animals, Apoptosis, Base Sequence, Cellulose, Central Nervous System, Ciona intestinalis, Computational Biology, Endocrine System, Gene Dosage, Gene Duplication, genes, Genes, Homeobox, Genome, Heart, Immunity, Molecular Sequence Data, Multigene Family, Muscle Proteins, Organizers, Embryonic, Phylogeny, Polymorphism, Genetic, Proteins, Sequence Analysis, DNA, Sequence Homology, Nucleic Acid, Species Specificity, Thyroid Gland, Urochordata, Vertebrates}, issn = {1095-9203}, doi = {10.1126/science.1080049}, author = {Dehal, Paramvir and Satou, Yutaka and Campbell, Robert K and Chapman, Jarrod and Degnan, Bernard and De Tomaso, Anthony and Davidson, Brad and Di Gregorio, Anna and Gelpke, Maarten and Goodstein, David M and Harafuji, Naoe and Hastings, Kenneth E M and Ho, Isaac and Hotta, Kohji and Huang, Wayne and Kawashima, Takeshi and Lemaire, Patrick and Martinez, Diego and Meinertzhagen, Ian A and Necula, Simona and Nonaka, Masaru and Putnam, Nik and Rash, Sam and Saiga, Hidetoshi and Satake, Masanobu and Terry, Astrid and Yamada, Lixy and Wang, Hong-Gang and Awazu, Satoko and Azumi, Kaoru and Boore, Jeffrey and Branno, Margherita and Chin-Bow, Stephen and DeSantis, Rosaria and Doyle, Sharon and Francino, Pilar and Keys, David N and Haga, Shinobu and Hayashi, Hiroko and Hino, Kyosuke and Imai, Kaoru S and Inaba, Kazuo and Kano, Shungo and Kobayashi, Kenji and Kobayashi, Mari and Lee, Byung-In and Makabe, Kazuhiro W and Manohar, Chitra and Matassi, Giorgio and Medina, Monica and Mochizuki, Yasuaki and Mount, Steve and Morishita, Tomomi and Miura, Sachiko and Nakayama, Akie and Nishizaka, Satoko and Nomoto, Hisayo and Ohta, Fumiko and Oishi, Kazuko and Rigoutsos, Isidore and Sano, Masako and Sasaki, Akane and Sasakura, Yasunori and Shoguchi, Eiichi and Shin-i, Tadasu and Spagnuolo, Antoinetta and Stainier, Didier and Suzuki, Miho M and Tassy, Olivier and Takatori, Naohito and Tokuoka, Miki and Yagi, Kasumi and Yoshizaki, Fumiko and Wada, Shuichi and Zhang, Cindy and Hyatt, P Douglas and Larimer, Frank and Detter, Chris and Doggett, Norman and Glavina, Tijana and Hawkins, Trevor and Richardson, Paul and Lucas, Susan and Kohara, Yuji and Levine, Michael and Satoh, Nori and Rokhsar, Daniel S} } @article {38224, title = {Effects of Global Climate on Infectious Disease: The Cholera Model}, journal = {Clinical Microbiology ReviewsClin. Microbiol. Rev.Clinical Microbiology ReviewsClin. Microbiol. Rev.}, volume = {15}, year = {2002}, type = {10.1128/CMR.15.4.757-770.2002}, abstract = {Recently, the role of the environment and climate in disease dynamics has become a subject of increasing interest to microbiologists, clinicians, epidemiologists, and ecologists. Much of the interest has been stimulated by the growing problems of antibiotic resistance among pathogens, emergence and/or reemergence of infectious diseases worldwide, the potential of bioterrorism, and the debate concerning climate change. Cholera, caused by Vibrio cholerae, lends itself to analyses of the role of climate in infectious disease, coupled to population dynamics of pathogenic microorganisms, for several reasons. First, the disease has a historical context linking it to specific seasons and biogeographical zones. In addition, the population dynamics of V. cholerae in the environment are strongly controlled by environmental factors, such as water temperature, salinity, and the presence of copepods, which are, in turn, controlled by larger-scale climate variability. In this review, the association between plankton and V. cholerae that has been documented over the last 20 years is discussed in support of the hypothesis that cholera shares properties of a vector-borne disease. In addition, a model for environmental transmission of cholera to humans in the context of climate variability is presented. The cholera model provides a template for future research on climate-sensitive diseases, allowing definition of critical parameters and offering a means of developing more sophisticated methods for prediction of disease outbreaks.}, isbn = {0893-8512, 1098-6618}, author = {Lipp, Erin K. and Huq, Anwar and Rita R. Colwell} } @proceedings {38249, title = {Experimental Construction of Very Large Scale DNA Databases with Associative Search}, volume = {7}, year = {2002}, month = {2002}, author = {Reif, J. H. and LaBean, T. H. and Pirrung, M. and Rana, V. S. and Guo, B. and Kingsford, Carl and Wickham, G. S.} } @article {38334, title = {Identification of non-autonomous non-LTR retrotransposons in the genome of Trypanosoma cruzi}, journal = {Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology}, volume = {124}, year = {2002}, type = {16/S0166-6851(02)00167-6}, abstract = {As observed for most eukaryotic cells, trypanosomatids contains non-LTR retrotransposons randomly inserted in the nuclear genome. Autonomous retroelements which, code for their own transposition, have been characterized in Trypanosoma brucei (ingi) and Trypanosoma cruzi (L1Tc), whereas non-autonomous retroelements have only been characterized in T. brucei (RIME). Here, we have characterized in the genome of Trypanosoma cruzi four complete copies of a non-autonomous non-LTR retrotransposon, called NARTc. This 0.26 kb NARTc element has the characteristics of non-LTR retrotransposons: the presence a poly(dA) tail and of a short flanking duplicated motif. Analysis of the Genome Survey Sequence databases indicated that the Trypanosoma cruzi haploid genome contains about 140 NARTc copies and about twice as many L1Tc copies. Interestingly, the NARTc and L1Tc retroelements share, with the Trypanosoma brucei ingi and RIME retrotransposons, a common sequence (the first 45 bp with 91\% identity), whereas the remaining sequences are very divergent. This suggests that these four trypanosome non-LTR retrotransposons were derived from the same common ancester and the sequence of their 5{\textquoteright}-extremity may have a functional role. In addition, the genome of Leishmania major contains the same conserved motif present in the trypanosome retroelements, whicle no transposable elements have been detected so far in Leishmania sp.}, keywords = {Ingi, L1Tc, Non-LTR retrotransposon, RIME, Trypanosoma brucei, Trypanosoma cruzi}, isbn = {0166-6851}, author = {Bringaud, Frederic and Garc{\'\i}a-P{\'e}rez, Jos{\'e} Luis and Heras, Sara R. and Ghedin, Elodie and Najib M. El-Sayed and Andersson, Bj{\"o}rn and Baltz, Th{\'e}o and Lopez, Manuel C.} } @article {49630, title = {Identification of non-autonomous non-LTR retrotransposons in the genome of Trypanosoma cruzi.}, journal = {Mol Biochem Parasitol}, volume = {124}, year = {2002}, month = {2002 Sep-Oct}, pages = {73-8}, abstract = {

As observed for most eukaryotic cells, trypanosomatids contains non-LTR retrotransposons randomly inserted in the nuclear genome. Autonomous retroelements which, code for their own transposition, have been characterized in Trypanosoma brucei (ingi) and Trypanosoma cruzi (L1Tc), whereas non-autonomous retroelements have only been characterized in T. brucei (RIME). Here, we have characterized in the genome of Trypanosoma cruzi four complete copies of a non-autonomous non-LTR retrotransposon, called NARTc. This 0.26 kb NARTc element has the characteristics of non-LTR retrotransposons: the presence a poly(dA) tail and of a short flanking duplicated motif. Analysis of the Genome Survey Sequence databases indicated that the Trypanosoma cruzi haploid genome contains about 140 NARTc copies and about twice as many L1Tc copies. Interestingly, the NARTc and L1Tc retroelements share, with the Trypanosoma brucei ingi and RIME retrotransposons, a common sequence (the first 45 bp with 91\% identity), whereas the remaining sequences are very divergent. This suggests that these four trypanosome non-LTR retrotransposons were derived from the same common ancester and the sequence of their 5{\textquoteright}-extremity may have a functional role. In addition, the genome of Leishmania major contains the same conserved motif present in the trypanosome retroelements, whicle no transposable elements have been detected so far in Leishmania sp.

}, keywords = {Animals, Base Sequence, Computational Biology, Genome, Protozoan, Long Interspersed Nucleotide Elements, Molecular Sequence Data, Retroelements, Short Interspersed Nucleotide Elements, Trypanosoma cruzi}, issn = {0166-6851}, author = {Bringaud, Frederic and Garc{\'\i}a-P{\'e}rez, Jos{\'e} Luis and Heras, Sara R and Ghedin, Elodie and El-Sayed, Najib M and Andersson, Bj{\"o}rn and Baltz, Th{\'e}o and Lopez, Manuel C} } @article {38337, title = {Identification of transcription factor binding sites in the human genome sequence}, journal = {Mammalian GenomeMammalian Genome}, volume = {13}, year = {2002}, abstract = {The identification of transcription factor binding sites (TFBS) is an important initial step in determining the DNA signals that regulate transcription of the genome. We tested the performance of three distinct computational methods for the identification of TFBS applied to the human genome sequence, as judged by their ability to recover the location of experimentally determined, and uniquely mapped, TFBS taken from the TRANSFAC database. These identification methods all attempt to filter the quantity of TFBS identified by aligning positional weight matrices that describe the binding site and employ either (i) a P-value threshold for accepting a site, (ii) an over-representation measure of neighboring sites, or (iii) conservation with the mouse genome and application of P-value thresholds. The results show that the best recognition of TFBS is achieved by combining the identification of TFBS in regions of human{\textendash}mouse conservation and also by applying a high stringency P-value to the TFBS identified in non-coding regions that are not conserved. Additionally, we find that only half of the 481 experimentally mapped sites can be found in sequence regions conserved with mouse, but the predictive power of the binding site identification method is up to threefold higher in the conserved regions.}, isbn = {0938-8990}, author = {Levy, Samuel and Sridhar Hannenhalli} } @article {38340, title = {In vitro adhesion to human cells by viable but nonculturable Enterococcus faecalis}, journal = {Current microbiologyCurrent microbiology}, volume = {45}, year = {2002}, type = {10.1007/s00284-001-0089-2}, abstract = {The ability of viable but nonculturable (VBNC) Enterococcus faecalis to adhere to Caco-2 and Girardi heart cultured cells and to urinary tract epithelial cells (ECs) was studied. Enterococci were harvested during the vegetative growth phase (early exponential and stationary), in the VBNC state, and after recovery of the ability to divide. VBNC bacteria maintained their adherence capability but the efficiency of attachment was reduced by about 50 to 70\%, depending on the target cell employed. The decrease was transient, since enterococci that regained their culturability showed adherence values similar to those observed for actively growing cells. Analysis of the invasive properties of E. faecalis revealed that the VBNC state caused a decrease in the number of bacteria that entered the cultured HEK cells as a result of the reduction in the number of adhering bacteria. These results highlight the importance of studies of the VBNC phenomenon, with respect to both microbial survival in the environment and the impact on human health.}, author = {Pruzzo, C. and Tarsi, R. and Lle{\`o}, M. M. and Signoretto, C. and Zampini, M. and Rita R. Colwell and Canepari, P.} } @article {38406, title = {A new, expressed multigene family containing a hot spot for insertion of retroelements is associated with polymorphic subtelomeric regions of Trypanosoma brucei}, journal = {Eukaryotic cellEukaryotic Cell}, volume = {1}, year = {2002}, author = {Bringaud, F. and Biteau, N. and Melville, S. E. and Hez, S. and Najib M. El-Sayed and Leech, V. and Berriman, M. and Hall, N. and Donelson, J. E. and Baltz, T.} } @article {49631, title = {A new, expressed multigene family containing a hot spot for insertion of retroelements is associated with polymorphic subtelomeric regions of Trypanosoma brucei.}, journal = {Eukaryot Cell}, volume = {1}, year = {2002}, month = {2002 Feb}, pages = {137-51}, abstract = {

We describe a novel gene family that forms clusters in subtelomeric regions of Trypanosoma brucei chromosomes and partially accounts for the observed clustering of retrotransposons. The ingi and ribosomal inserted mobile element (RIME) non-LTR retrotransposons share 250 bp at both extremities and are the most abundant putatively mobile elements, with about 500 copies per haploid genome. From cDNA clones and subsequently in the T. brucei genomic DNA databases, we identified 52 homologous gene and pseudogene sequences, 16 of which contain a RIME and/or ingi retrotransposon inserted at exactly the same relative position. Here these genes are called the RHS family, for retrotransposon hot spot. Comparison of the protein sequences encoded by RHS genes (21 copies) and pseudogenes (24 copies) revealed a conserved central region containing an ATP/GTP-binding motif and the RIME/ingi insertion site. The RHS proteins share between 13 and 96\% identity, and six subfamilies, RHS1 to RHS6, can be defined on the basis of their divergent C-terminal domains. Immunofluorescence and Western blot analyses using RHS subfamily-specific immune sera show that RHS proteins are constitutively expressed and occur mainly in the nucleus. Analysis of Genome Survey Sequence databases indicated that the Trypanosoma brucei diploid genome contains about 280 RHS (pseudo)genes. Among the 52 identified RHS (pseudo)genes, 48 copies are in three RHS clusters located in subtelomeric regions of chromosomes Ia and II and adjacent to the active bloodstream form expression site in T. brucei strain TREU927/4 GUTat10.1. RHS genes comprise the remaining sequence of the size-polymorphic "repetitive region" described for T. brucei chromosome I, and a homologous gene family is present in the Trypanosoma cruzi genome.

}, keywords = {Amino Acid Sequence, Animals, Base Sequence, Cloning, Molecular, DNA Primers, DNA, Protozoan, Escherichia coli, Genes, Protozoan, Molecular Sequence Data, Multigene Family, Mutagenesis, Insertional, Phylogeny, Polymorphism, Genetic, Protozoan Proteins, Pseudogenes, Retroelements, sequence alignment, Sequence Homology, Amino Acid, Telomere, Trypanosoma brucei brucei, Trypanosoma cruzi}, issn = {1535-9778}, author = {Bringaud, Frederic and Biteau, Nicolas and Melville, Sara E and Hez, St{\'e}phanie and El-Sayed, Najib M and Leech, Vanessa and Berriman, Matthew and Hall, Neil and Donelson, John E and Baltz, Th{\'e}o} } @article {38430, title = {Phylogenetic analysis based on 18S ribosomal RNA gene sequences supports the existence of class Polyacanthocephala (Acanthocephala)}, journal = {Mol Phylogenet EvolMol Phylogenet Evol}, volume = {23}, year = {2002}, type = {10.1016/S1055-7903(02)00020-9}, abstract = {Members of phylum Acanthocephala are parasites of vertebrates and arthropods and are distributed worldwide. The phylum has traditionally been divided into three classes, Archiacanthocephala, Palaeacanthocephala, and Eoacanthocephala; a fourth class, Polyacanthocephala, has been recently proposed. However, erection of this new class, based on morphological characters, has been controversial. We sequenced the near complete 18S rRNA gene of Polyacanthorhynchus caballeroi (Polyacanthocephala) and Rhadinorhynchus sp. (Palaeacanthocephala); these sequences were aligned with another 21 sequences of acanthocephalans representing the three widely recognized classes of the phylum and with 16 sequences from outgroup taxa. Phylogenetic relationships inferred by maximum-likelihood and maximum-parsimony analyses showed Archiacanthocephala as the most basal group within the phylum, whereas classes Polyacanthocephala + Eoacanthocephala formed a monophyletic clade, with Palaeacanthocephala as its sister group. These results are consistent with the view of Polyacanthocephala representing an independent class within Acanthocephala.}, author = {Garc{\'\i}a-Varela, M. and Michael P. Cummings and P{\'e}rez-Ponce de Le{\'o}n, G. and Gardner, S. L. and Laclette, J. P.} } @article {38447, title = {Predicting Transcription Factor Synergism}, journal = {Nucleic Acids ResearchNucl. Acids Res.Nucleic Acids ResearchNucl. Acids Res.}, volume = {30}, year = {2002}, type = {10.1093/nar/gkf535}, abstract = {Transcriptional regulation is mediated by a battery of transcription factor (TF) proteins, that form complexes involving protein{\textendash}protein and protein{\textendash}DNA interactions. Individual TFs bind to their cognate cis-elements or transcription factor-binding sites (TFBS). TFBS are organized on the DNA proximal to the gene in groups confined to a few hundred base pair regions. These groups are referred to as modules. Various modules work together to provide the combinatorial regulation of gene transcription in response to various developmental and environmental conditions. The sets of modules constitute a promoter model. Determining the TFs that preferentially work in concert as part of a module is an essential component of understanding transcriptional regulation. The TFs that act synergistically in such a fashion are likely to have their cis-elements co-localized on the genome at specific distances apart. We exploit this notion to predict TF pairs that are likely to be part of a transcriptional module on the human genome sequence. The computational method is validated statistically, using known interacting pairs extracted from the literature. There are 251 TFBS pairs up to 50 bp apart and 70 TFBS pairs up to 200 bp apart that score higher than any of the known synergistic pairs. Further investigation of 50 pairs randomly selected from each of these two sets using PubMed queries provided additional supporting evidence from the existing biological literature suggesting TF synergism for these novel pairs.}, isbn = {0305-1048, 1362-4962}, author = {Sridhar Hannenhalli and Levy, Samuel} } @article {38492, title = {Sequence of Plasmodium falciparum chromosomes 2, 10, 11 and 14}, journal = {NatureNature}, volume = {419}, year = {2002}, note = {http://www.ncbi.nlm.nih.gov/pubmed/12368868?dopt=Abstract}, type = {10.1038/nature01094}, abstract = {The mosquito-borne malaria parasite Plasmodium falciparum kills an estimated 0.7-2.7 million people every year, primarily children in sub-Saharan Africa. Without effective interventions, a variety of factors-including the spread of parasites resistant to antimalarial drugs and the increasing insecticide resistance of mosquitoes-may cause the number of malaria cases to double over the next two decades. To stimulate basic research and facilitate the development of new drugs and vaccines, the genome of Plasmodium falciparum clone 3D7 has been sequenced using a chromosome-by-chromosome shotgun strategy. We report here the nucleotide sequences of chromosomes 10, 11 and 14, and a re-analysis of the chromosome 2 sequence. These chromosomes represent about 35\% of the 23-megabase P. falciparum genome.}, keywords = {Animals, Chromosomes, DNA, Protozoan, Genome, Protozoan, Plasmodium falciparum, Proteome, Protozoan Proteins, Sequence Analysis, DNA}, author = {Gardner, Malcolm J. and Shallom, Shamira J. and Carlton, Jane M. and Salzberg, Steven L. and Nene, Vishvanath and Shoaibi, Azadeh and Ciecko, Anne and Lynn, Jeffery and Rizzo, Michael and Weaver, Bruce and Jarrahi, Behnam and Brenner, Michael and Parvizi, Babak and Tallon, Luke and Moazzez, Azita and Granger, David and Fujii, Claire and Hansen, Cheryl and Pederson, James and Feldblyum, Tamara and Peterson, Jeremy and Suh, Bernard and Angiuoli, Sam and Pertea, Mihaela and Allen, Jonathan and J. Selengut and White, Owen and Cummings, Leda M. and Smith, Hamilton O. and Adams, Mark D. and Venter, J. Craig and Carucci, Daniel J. and Hoffman, Stephen L. and Fraser, Claire M.} } @article {38504, title = {Simple Procedure for Rapid Identification of Vibrio Cholerae from the Aquatic Environment}, journal = {Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol.}, volume = {68}, year = {2002}, type = {10.1128/AEM.68.2.995-998.2002}, abstract = {Biochemical tests commonly used to screen for Vibrio cholerae in environmental samples were evaluated, and we found that a combination of alkaline peptone enrichment followed by streaking on thiosulfate citrate bile salts sucrose agar and testing for arginine dihydrolase activity and esculin hydrolysis was an effective rapid technique to screen for aquatic environmental V. cholerae. This technique provided 100\% sensitivity and >=70\% specificity.}, isbn = {0099-2240, 1098-5336}, author = {Choopun, Nipa and Louis, Val{\'e}rie and Huq, Anwar and Rita R. Colwell} } @article {38113, title = {Analysis of a donor gene region for a variant surface glycoprotein and its expression site in African trypanosomes}, journal = {Nucleic acids researchNucleic Acids Research}, volume = {29}, year = {2001}, author = {LaCount, D. J. and Najib M. El-Sayed and Kaul, S. and Wanless, D. and Turner, C. M. R. and Donelson, J. E.} } @conference {49569, title = {Automatically tracking and analyzing the behavior of live insect colonies}, booktitle = {the fifth international conferenceProceedings of the fifth international conference on Autonomous agents - AGENTS {\textquoteright}01}, year = {2001}, publisher = {ACM Press}, organization = {ACM Press}, address = {Montreal, Quebec, CanadaNew York, New York, USA}, isbn = {158113326X}, doi = {10.1145/37573510.1145/375735.376434}, url = {http://portal.acm.org/citation.cfm?doid=375735http://portal.acm.org/citation.cfm?doid=375735.376434}, author = {Balch, Tucker and Khan, Zia and Veloso, Manuela} } @article {38230, title = {Enrichment of Regulatory Signals in Conserved Non-Coding Genomic Sequence}, journal = {BioinformaticsBioinformaticsBioinformaticsBioinformatics}, volume = {17}, year = {2001}, type = {10.1093/bioinformatics/17.10.871}, abstract = {Motivation: Whole genome shotgun sequencing strategies generate sequence data prior to the application of assembly methodologies that result in contiguous sequence. Sequence reads can be employed to indicate regions of conservation between closely related species for which only one genome has been assembled. Consequently, by using pairwise sequence alignments methods it is possible to identify novel, non-repetitive, conserved segments in non-coding sequence that exist between the assembled human genome and mouse whole genome shotgun sequencing fragments. Conserved non-coding regions identify potentially functional DNA that could be involved in transcriptional regulation.Results: Local sequence alignment methods were applied employing mouse fragments and the assembled human genome. In addition, transcription factor binding sites were detected by aligning their corresponding positional weight matrices to the sequence regions. These methods were applied to a set of transcripts corresponding to 502 genes associated with a variety of different human diseases taken from the Online Mendelian Inheritance in Man database. Using statistical arguments we have shown that conserved non-coding segments contain an enrichment of transcription factor binding sites when compared to the sequence background in which the conserved segments are located. This enrichment of binding sites was not observed in coding sequence. Conserved non-coding segments are not extensively repeated in the genome and therefore their identification provides a rapid means of finding genes with related conserved regions, and consequently potentially related regulatory mechanism. Conserved segments in upstream regions are found to contain binding sites that are co-localized in a manner consistent with experimentally known transcription factor pairwise co-occurrences and afford the identification of novel co-occurring Transcription Factor (TF) pairs. This study provides a methodology and more evidence to suggest that conserved non-coding regions are biologically significant since they contain a statistical enrichment of regulatory signals and pairs of signals that enable the construction of regulatory models for human genes. Contact: samuel.levy@celera.com}, isbn = {1367-4803, 1460-2059}, author = {Levy, Samuel and Sridhar Hannenhalli and Workman, Christopher} } @article {38451, title = {Promoter prediction in the human genome}, journal = {BioinformaticsBioinformatics}, volume = {17}, year = {2001}, type = {10.1093/bioinformatics/17.suppl_1.S90}, abstract = {Computational prediction of eukaryotic polII promoters has been one of the most elusive problems despite considerable effort devoted to the study. Researchers have looked for various types of signals around the transcriptional start site (TSS), viz. oligo-nucleotide statistics, potential binding sites for core factors, clusters of binding sites, proximity to CpG islands etc.. The proximity of CpG islands to gene starts is now a well established fact, although until recently, it was based on very little genomic data. In this work we explore the possibility of enhancing the promoter prediction accuracy by combining CpG island information with a few other, biologically motivated, seemingly independent signals, that cover most of the known knowledge. We benchmarked the method on a much larger genomic datasets compared to previous studies. We were able to improve slightly upon current prediction accuracy. Furthermore, we observe that CpG islands are the most dominant signals and the other signals do not improve the prediction. This suggests that the computational prediction of promoters for genes with no associated CpG-island (typically having tissue-specific expression) looking only at the immediate neighborhood of the TSS may not even be possible. We suggest some biological experiments and studies to better understand the biology of transcription.}, isbn = {1367-4803, 1460-2059}, author = {Sridhar Hannenhalli and Levy, S.} } @article {38143, title = {Carbonic anhydrase III: the phosphatase activity is extrinsic}, journal = {Archives of biochemistry and biophysicsArchives of biochemistry and biophysics}, volume = {377}, year = {2000}, note = {http://www.ncbi.nlm.nih.gov/pubmed/10845711?dopt=Abstract}, type = {10.1006/abbi.2000.1793}, abstract = {The carbonic anhydrases reversibly hydrate carbon dioxide to yield bicarbonate and hydrogen ion. They have a variety of physiological functions, although the specific roles of each of the 10 known isozymes are unclear. Carbonic anhydrase isozyme III is particularly rich in skeletal muscle and adipocytes, and it is unique among the isozymes in also exhibiting phosphatase activity. Previously published studies provided evidence that the phosphatase activity was intrinsic to carbonic anhydrase III, that it had specificity for tyrosine phosphate, and that activity was regulated by reversible glutathionylation of cysteine186. To study the mechanism of this phosphatase, we cloned and expressed the rat liver carbonic anhydrase III. The purified recombinant had the same specific activity as the carbonic anhydrase purified from rat liver, but it had virtually no phosphatase activity. We attempted to identify an activator of the phosphatase in rat liver and found a protein of approximately 14 kDa, the amount of which correlated with the phosphatase activity of the carbonic anhydrase III fractions. It was identified as liver fatty acid binding protein, which was then purified to test for activity as an activator of the phosphatase and for protein-protein interaction, but neither binding nor activation could be demonstrated. Immunoprecipitation experiments established that carbonic anhydrase III could be separated from the phosphatase activity. Finally, adding additional purification steps completely separated the phosphatase activity from the carbonic anhydrase activity. We conclude that the phosphatase activity previously considered to be intrinsic to carbonic anhydrase III is actually extrinsic. Thus, this isozyme exhibits only the carbon dioxide hydratase and esterase activities characteristic of the other mammalian isozymes, and the phosphatase previously shown to be activated by glutathionylation is not carbonic anhydrase III.}, keywords = {Animals, Carbonic Anhydrases, Chromatography, High Pressure Liquid, Cloning, Molecular, Enzyme Activation, Glutathione, Kinetics, Liver, Male, Muscles, Phosphoric Monoester Hydrolases, Precipitin Tests, Rabbits, Rats, Rats, Inbred F344, Recombinant Proteins, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Time factors}, author = {Kim, G. and J. Selengut and Levine, R. L.} } @article {49692, title = {The genome sequence of Drosophila melanogaster.}, journal = {Science}, volume = {287}, year = {2000}, month = {2000 Mar 24}, pages = {2185-95}, abstract = {

The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

}, keywords = {Animals, Biological Transport, Chromatin, Cloning, Molecular, Computational Biology, Contig Mapping, Cytochrome P-450 Enzyme System, DNA Repair, DNA Replication, Drosophila melanogaster, Euchromatin, Gene Library, Genes, Insect, Genome, Heterochromatin, Insect Proteins, Nuclear Proteins, Protein Biosynthesis, Sequence Analysis, DNA, Transcription, Genetic}, issn = {0036-8075}, author = {Adams, M D and Celniker, S E and Holt, R A and Evans, C A and Gocayne, J D and Amanatides, P G and Scherer, S E and Li, P W and Hoskins, R A and Galle, R F and George, R A and Lewis, S E and Richards, S and Ashburner, M and Henderson, S N and Sutton, G G and Wortman, J R and Yandell, M D and Zhang, Q and Chen, L X and Brandon, R C and Rogers, Y H and Blazej, R G and Champe, M and Pfeiffer, B D and Wan, K H and Doyle, C and Baxter, E G and Helt, G and Nelson, C R and Gabor, G L and Abril, J F and Agbayani, A and An, H J and Andrews-Pfannkoch, C and Baldwin, D and Ballew, R M and Basu, A and Baxendale, J and Bayraktaroglu, L and Beasley, E M and Beeson, K Y and Benos, P V and Berman, B P and Bhandari, D and Bolshakov, S and Borkova, D and Botchan, M R and Bouck, J and Brokstein, P and Brottier, P and Burtis, K C and Busam, D A and Butler, H and Cadieu, E and Center, A and Chandra, I and Cherry, J M and Cawley, S and Dahlke, C and Davenport, L B and Davies, P and de Pablos, B and Delcher, A and Deng, Z and Mays, A D and Dew, I and Dietz, S M and Dodson, K and Doup, L E and Downes, M and Dugan-Rocha, S and Dunkov, B C and Dunn, P and Durbin, K J and Evangelista, C C and Ferraz, C and Ferriera, S and Fleischmann, W and Fosler, C and Gabrielian, A E and Garg, N S and Gelbart, W M and Glasser, K and Glodek, A and Gong, F and Gorrell, J H and Gu, Z and Guan, P and Harris, M and Harris, N L and Harvey, D and Heiman, T J and Hernandez, J R and Houck, J and Hostin, D and Houston, K A and Howland, T J and Wei, M H and Ibegwam, C and Jalali, M and Kalush, F and Karpen, G H and Ke, Z and Kennison, J A and Ketchum, K A and Kimmel, B E and Kodira, C D and Kraft, C and Kravitz, S and Kulp, D and Lai, Z and Lasko, P and Lei, Y and Levitsky, A A and Li, J and Li, Z and Liang, Y and Lin, X and Liu, X and Mattei, B and McIntosh, T C and McLeod, M P and McPherson, D and Merkulov, G and Milshina, N V and Mobarry, C and Morris, J and Moshrefi, A and Mount, S M and Moy, M and Murphy, B and Murphy, L and Muzny, D M and Nelson, D L and Nelson, D R and Nelson, K A and Nixon, K and Nusskern, D R and Pacleb, J M and Palazzolo, M and Pittman, G S and Pan, S and Pollard, J and Puri, V and Reese, M G and Reinert, K and Remington, K and Saunders, R D and Scheeler, F and Shen, H and Shue, B C and Sid{\'e}n-Kiamos, I and Simpson, M and Skupski, M P and Smith, T and Spier, E and Spradling, A C and Stapleton, M and Strong, R and Sun, E and Svirskas, R and Tector, C and Turner, R and Venter, E and Wang, A H and Wang, X and Wang, Z Y and Wassarman, D A and Weinstock, G M and Weissenbach, J and Williams, S M and Worley, K C and Wu, D and Yang, S and Yao, Q A and Ye, J and Yeh, R F and Zaveri, J S and Zhan, M and Zhang, G and Zhao, Q and Zheng, L and Zheng, X H and Zhong, F N and Zhong, W and Zhou, X and Zhu, S and Zhu, X and Smith, H O and Gibbs, R A and Myers, E W and Rubin, G M and Venter, J C} } @article {38369, title = {MDP-1: A novel eukaryotic magnesium-dependent phosphatase}, journal = {BiochemistryBiochemistry}, volume = {39}, year = {2000}, note = {http://www.ncbi.nlm.nih.gov/pubmed/10889041?dopt=Abstract}, abstract = {We report here the purification, cloning, expression, and characterization of a novel phosphatase, MDP-1. In the course of investigating the reported acid phosphatase activity of carbonic anhydrase III preparations, several discrete phosphatases were discerned. One of these, a magnesium-dependent species of 18.6 kDa, was purified to homogeneity and yielded several peptide sequences from which the parent gene was identified by database searching. Although orthologous genes were identified in fungi and plants as well as mammalian species, there was no apparent homology to any known family of phosphatases. The enzyme was expressed in Escherichia coli with a fusion tag and purified by affinity methods. The recombinant enzyme showed magnesium-dependent acid phosphatase activity comparable to the originally isolated rabbit protein. The enzyme catalyzes the rapid hydrolysis of p-nitrophenyl phosphate, ribose-5-phosphate, and phosphotyrosine. The selectivity for phosphotyrosine over phosphoserine or phosphothreonine is considerable, but the enzyme did not show activity toward five phosphotyrosine-containing peptides. None of the various substrates assayed (including various nucleotide, sugar, amino acid and peptide phosphates, phosphoinositides, and phosphodiesters) exhibited K(M) values lower than 1 mM, and many showed negligible rates of hydrolysis. The enzyme is inhibited by vanadate and fluoride but not by azide, cyanide, calcium, lithium, or tartaric acid. Chemical labeling, refolding, dialysis, and mutagenesis experiments suggest that the enzymatic mechanism is not dependent on cysteine, histidine, or nonmagnesium metal ions. In recognition of these observations, the enzyme has been given the name magnesium-dependent phosphatase-1 (MDP-1).}, keywords = {Amino Acid Sequence, Animals, Catalysis, Cations, Chromatography, Affinity, Cloning, Molecular, Cysteine, Enzyme Inhibitors, Histidine, Hydrogen-Ion Concentration, Magnesium, Mice, Molecular Sequence Data, Phosphoprotein Phosphatases, Protein Phosphatase 1, Rabbits, Sequence Analysis, Protein, Sequence Homology, Amino Acid, Substrate Specificity}, author = {J. Selengut and Levine, R. L.} } @article {38433, title = {Phylogenetic relationships of Acanthocephala based on analysis of 18S ribosomal RNA gene sequences}, journal = {J Mol EvolJ Mol Evol}, volume = {50}, year = {2000}, abstract = {Acanthocephala (thorny-headed worms) is a phylum of endoparasites of vertebrates and arthropods, included among the most phylogenetically basal tripoblastic pseudocoelomates. The phylum is divided into three classes: Archiacanthocephala, Palaeacanthocephala, and Eoacanthocephala. These classes are distinguished by morphological characters such as location of lacunar canals, persistence of ligament sacs in females, number and type of cement glands in males, number and size of proboscis hooks, host taxonomy, and ecology. To understand better the phylogenetic relationships within Acanthocephala, and between Acanthocephala and Rotifera, we sequenced the nearly complete 18S rRNA genes of nine species from the three classes of Acanthocephala and four species of Rotifera from the classes Bdelloidea and Monogononta. Phylogenetic relationships were inferred by maximum-likelihood analyses of these new sequences and others previously determined. The analyses showed that Acanthocephala is the sister group to a clade including Eoacanthocephala and Palaeacanthocephala. Archiacanthocephala exhibited a slower rate of evolution at the nucleotide level, as evidenced by shorter branch lengths for the group. We found statistically significant support for the monophyly of Rotifera, represented in our analysis by species from the clade Eurotatoria, which includes the classes Bdelloidea and Monogononta. Eurotatoria also appears as the sister group to Acanthocephala.}, author = {Garc{\'\i}a-Varela, M. and P{\'e}rez-Ponce de Le{\'o}n, G. and de la Torre, P. and Michael P. Cummings and Sarma, S. S. and Laclette, J. P.} } @article {38435, title = {Phylogenetic relationships of platyhelminthes based on 18S ribosomal gene sequences}, journal = {Mol Phylogenet EvolMol Phylogenet Evol}, volume = {10}, year = {1998}, type = {10.1006/mpev.1997.0483}, abstract = {Nucleotide sequences of 18S ribosomal RNA from 71 species of Platyhelminthes, the flatworms, were analyzed using maximum likelihood, and the resulting phylogenetic trees were compared with previous phylogenetic hypotheses. Analyses including 15 outgroup species belonging to eight other phyla show that Platyhelminthes are monophyletic with the exception of a sequence putatively from Acoela sp., Lecithoepitheliata, Polycladida, Tricladida, Trematoda (Aspidobothrii + Digenea), Monogenea, and Cestoda (Gyrocotylidea + Amphilinidea + Eucestoda) are monophyletic groups. Catenulids form the sister group to the rest of platyhelminths, whereas a complex clade formed by Acoela, Tricladida, "Dalyellioida", and perhaps "Typhloplanoida" is sister to Neodermata. "Typhloplanoida" does not appear to be monophyletic; Fecampiida does not appear to belong within "Dalyellioida," nor Kalyptorhynchia within "Typhloplanoida." Trematoda is the sister group to the rest of Neodermata, and Monogenea is sister group to Cestoda. Within Trematoda, Aspidobothrii is the sister group of Digenea and Heronimidae is the most basal family in Digenea. Our trees support the hypothesis that parasitism evolved at least twice in Platyhelminthes, once in the ancestor to Neodermata and again in the ancestor of Fecampiida, independently to the ancestor of putatively parasitic "Dalyellioida."}, author = {Campos, A. and Michael P. Cummings and Reyes, J. L. and Laclette, J. P.} } @article {38548, title = {Trends in the early careers of life scientists - Preface and executive summary}, journal = {Mol Biol CellMol Biol Cell}, volume = {9}, year = {1998}, author = {Tilghman, S. and Astin, H. S. and Brinkley, W. and Chilton, M. D. and Michael P. Cummings and Ehrenberg, R. G. and Fox, M. F. and Glenn, K. and Green, P. J. and Hans, S. and Kelman, A. and LaPidus, J. and Levin, B. and McIntosh, J. R. and Riecken, H. and Stephen, P. E.} } @article {38174, title = {Computational studies of synaptic alterations in Alzheimer{\textquoteright}s disease}, journal = {Neural modeling of brain and cognitive disordersNeural modeling of brain and cognitive disorders}, year = {1996}, author = {Ruppin, E. and Horn, D. and Levy, N. and Reggia, James A.} } @article {38245, title = {Evolutionary biology of parasitic platyhelminths: The role of molecular phylogenetics}, journal = {Parasitol TodayParasitol Today}, volume = {12}, year = {1996}, abstract = {As our appreciation of the diversity within the flatworms has grown, so too has our curiosity about the ways in which these varied creatures are related to one another. In particular, the parasitic groups (trematodes, cestodes and monogeneans have been the focus of enquiry. Until recently, morphology, anatomy and life histories have provided the raw data for building hypotheses on relationships. Now, ultrastructural evidence, and most recently, molecular data from nucleic acid sequences, have been brought to bear on the topic. Here, David Blair, Andr{\'e}s Campos, Michael Cummings and Juan Pedro Laclette discuss the ways in which molecular data, in particular, are helping us recognize the various lineages of flatworms.}, author = {Blair, D. and Campos, A. and Michael P. Cummings and Laclette, J. P.} } @article {38442, title = {Positional sequencing by hybridization}, journal = {Computer applications in the biosciences : CABIOSComputer applications in the biosciences : CABIOS}, volume = {12}, year = {1996}, type = {10.1093/bioinformatics/12.1.19}, abstract = {Sequencing by hybridization (SBH) is a promising alternative to the classical DNA sequencing approaches. However, the resolving power of SBH is rather low: with 64kb sequencing chips, unknown DNA fragments only as long as 200 bp can be reconstructed in a single SBH experiment. To improve the resolving power of SBH, positional SBH (PSBH) has recently been suggested; this allows (with additional experimental work) approximate positions of every l-tuple in a target DNA fragment to be measured. We study the positional Eulerian path problem motivated by PSBH. The input to the positional eulerian path problem is an Eulerian graph G( V, E) in which every edge has an associated range of integers and the problem is to find an Eulerian path el, {\textellipsis}, e|E| in G such that the range of ei, contains i. We show that the positional Eulerian path problem is NP-complete even when the maximum out-degree (in-degree) of any vertex in the graph is 2. On a positive note we present polynomial algorithms to solve a special case of PSBH (bounded PSBH), where the range of the allowed positions for any edge is bounded by a constant (it corresponds to accurate experimental measurements of positions in PSBH). Moreover, if the positions of every l-tuple in an unknown DNA fragment of length n are measured with O(log n) error, then our algorithm runs in polynomial time. We also present an estimate of the resolving power of PSBH for a more realistic case when positions are measured with Θ(n) error.}, author = {Sridhar Hannenhalli and Feldman, William and Lewis, Herbert F. and Skiena, Steven S. and Pevzner, Pavel A.} } @article {49698, title = {Suppressor U1 snRNAs in Drosophila.}, journal = {Genetics}, volume = {138}, year = {1994}, month = {1994 Oct}, pages = {365-78}, abstract = {

Although the role of U1 small nuclear RNAs (snRNAs) in 5{\textquoteright} splice site recognition is well established, suppressor U1 snRNAs active in intact multicellular animals have been lacking. Here we describe suppression of a 5{\textquoteright} splice site mutation in the Drosophila melanogaster white gene (wDR18) by compensatory changes in U1 snRNA. Mutation of positions -1 and +6 of the 5{\textquoteright} splice site of the second intron (ACG[GTGAGT to ACC]GTGAGC) results in the accumulation of RNA retaining this 74-nucleotide intron in both transfected cells and transgenic flies. U1-3G, a suppressor U1 snRNA which restores base-pairing at position +6 of the mutant intron, increases the ratio of spliced to unspliced wDR18 RNA up to fivefold in transfected Schneider cells and increases eye pigmentation in wDR18 flies. U1-9G, which targets position -1, suppresses wDR18 in transfected cells less well. U1-3G,9G has the same effect as U1-3G although it accumulates to lower levels. Suppression of wDR18 has revealed that the U1b embryonic variant (G134 to U) is active in Schneider cells and pupal eye discs. However, the combination of 9G with 134U leads to reduced accumulation of both U1b-9G and U1b-3G,9G, possibly because nucleotides 9 and 134 both participate in a potential long-range intramolecular base-pairing interaction. High levels of functional U1-3G suppressor reduce both viability and fertility in transformed flies. These results show that, despite the difficulties inherent in stably altering splice site selection in multicellular organisms, it is possible to obtain suppressor U1 snRNAs in flies.

}, keywords = {Alternative Splicing, Animals, Base Sequence, Cell Line, Cell Nucleus, DNA Primers, Drosophila melanogaster, Female, Genes, Suppressor, Genetic Variation, GENOTYPE, Introns, Male, Molecular Sequence Data, Mutagenesis, Site-Directed, Nucleic Acid Conformation, Oligodeoxyribonucleotides, PHENOTYPE, Recombinant Proteins, Ribonucleoprotein, U1 Small Nuclear, RNA, Small Nuclear, Transfection, Transformation, Genetic}, issn = {0016-6731}, author = {Lo, P C and Roy, D and Mount, S M} } @article {49701, title = {Species-specific signals for the splicing of a short Drosophila intron in vitro.}, journal = {Mol Cell Biol}, volume = {13}, year = {1993}, month = {1993 Feb}, pages = {1104-18}, abstract = {

The effects of branchpoint sequence, the pyrimidine stretch, and intron size on the splicing efficiency of the Drosophila white gene second intron were examined in nuclear extracts from Drosophila and human cells. This 74-nucleotide intron is typical of many Drosophila introns in that it lacks a significant pyrimidine stretch and is below the minimum size required for splicing in human nuclear extracts. Alteration of sequences of adjacent to the 3{\textquoteright} splice site to create a pyrimidine stretch was necessary for splicing in human, but not Drosophila, extracts. Increasing the size of this intron with insertions between the 5{\textquoteright} splice site and the branchpoint greatly reduced the efficiency of splicing of introns longer than 79 nucleotides in Drosophila extracts but had an opposite effect in human extracts, in which introns longer than 78 nucleotides were spliced with much greater efficiency. The white-apricot copia insertion is immediately adjacent to the branchpoint normally used in the splicing of this intron, and a copia long terminal repeat insertion prevents splicing in Drosophila, but not human, extracts. However, a consensus branchpoint does not restore the splicing of introns containing the copia long terminal repeat, and alteration of the wild-type branchpoint sequence alone does not eliminate splicing. These results demonstrate species specificity of splicing signals, particularly pyrimidine stretch and size requirements, and raise the possibility that variant mechanisms not found in mammals may operate in the splicing of small introns in Drosophila and possibly other species.

}, keywords = {Animals, Base Sequence, Cell Nucleus, Consensus Sequence, DNA, DNA Transposable Elements, Drosophila, Drosophila Proteins, Electrophoresis, Polyacrylamide Gel, HeLa Cells, HUMANS, Introns, Molecular Sequence Data, Mutation, Peptide Hydrolases, Proteins, Regulatory Sequences, Nucleic Acid, Retroelements, RNA Splicing, Species Specificity}, issn = {0270-7306}, author = {Guo, M and Lo, P C and Mount, S M} } @article {49704, title = {Drosophila melanogaster genes for U1 snRNA variants and their expression during development.}, journal = {Nucleic Acids Res}, volume = {18}, year = {1990}, month = {1990 Dec 11}, pages = {6971-9}, abstract = {

We have cloned and characterized a complete set of seven U1-related sequences from Drosophila melanogaster. These sequences are located at the three cytogenetic loci 21D, 82E, and 95C. Three of these sequences have been previously studied: one U1 gene at 21D which encodes the prototype U1 sequence (U1a), one U1 gene at 82E which encodes a U1 variant with a single nucleotide substitution (U1b), and a pseudogene at 82E. The four previously uncharacterized genes are another U1b gene at 82E, two additional U1a genes at 95C, and a U1 gene at 95C which encodes a new variant (U1c) with a distinct single nucleotide change relative to U1a. Three blocks of 5{\textquoteright} flanking sequence similarity are common to all six full length genes. Using specific primer extension assays, we have observed that the U1b RNA is expressed in Drosophila Kc cells and is associated with snRNP proteins, suggesting that the U1b-containing snRNP particles are able to participate in the process of pre-mRNA splicing. We have also examined the expression throughout Drosophila development of the two U1 variants relative to the prototype sequence. The U1c variant is undetectable by our methods, while the U1b variant exhibits a primarily embryonic pattern reminiscent of the expression of certain U1 variants in sea urchin, Xenopus, and mouse.

}, keywords = {Animals, Base Sequence, Blotting, Southern, Cloning, Molecular, Drosophila melanogaster, Gene Expression Regulation, genes, Genetic Variation, Molecular Sequence Data, Nucleic Acid Conformation, Pseudogenes, Restriction Mapping, RNA, Small Nuclear}, issn = {0305-1048}, author = {Lo, P C and Mount, S M} } @article {49706, title = {Structure and expression of the Drosophila melanogaster gene for the U1 small nuclear ribonucleoprotein particle 70K protein.}, journal = {Mol Cell Biol}, volume = {10}, year = {1990}, month = {1990 Jun}, pages = {2492-502}, abstract = {

A genomic clone encoding the Drosophila U1 small nuclear ribonucleoprotein particle 70K protein was isolated by hybridization with a human U1 small nuclear ribonucleoprotein particle 70K protein cDNA. Southern blot and in situ hybridizations showed that this U1 70K gene is unique in the Drosophila genome, residing at cytological position 27D1,2. Polyadenylated transcripts of 1.9 and 3.1 kilobases were observed. While the 1.9-kilobase mRNA is always more abundant, the ratio of these two transcripts is developmentally regulated. Analysis of cDNA and genomic sequences indicated that these two RNAs encode an identical protein with a predicted molecular weight of 52,879. Comparison of the U1 70K proteins predicted from Drosophila, human, and Xenopus cDNAs revealed 68\% amino acid identity in the most amino-terminal 214 amino acids, which include a sequence motif common to many proteins which bind RNA. The carboxy-terminal half is less well conserved but is highly charged and contains distinctive arginine-rich regions in all three species. These arginine-rich regions contain stretches of arginine-serine dipeptides like those found in transformer, transformer-2, and suppressor-of-white-apricot proteins, all of which have been identified as regulators of mRNA splicing in Drosophila melanogaster.

}, keywords = {Amino Acid Sequence, Animals, Base Sequence, Blotting, Northern, Blotting, Southern, Cloning, Molecular, DNA, Drosophila melanogaster, Gene expression, Gene Library, genes, HUMANS, Molecular Sequence Data, Molecular Weight, Oligonucleotide Probes, Poly A, Ribonucleoproteins, Ribonucleoproteins, Small Nuclear, RNA, RNA, Messenger, Sequence Homology, Nucleic Acid, Xenopus}, issn = {0270-7306}, author = {Mancebo, R and Lo, P C and Mount, S M} } @article {49716, title = {Small ribonucleoproteins from eukaryotes: structures and roles in RNA biogenesis.}, journal = {Cold Spring Harb Symp Quant Biol}, volume = {47 Pt 2}, year = {1983}, month = {1983}, pages = {893-900}, keywords = {Animals, Base Sequence, HeLa Cells, HUMANS, Mice, Molecular Weight, Nucleic Acid Conformation, Nucleic Acid Hybridization, Nucleoproteins, Ribonucleoproteins, Ribonucleoproteins, Small Nuclear, RNA Polymerase III, Transcription, Genetic}, issn = {0091-7451}, author = {Steitz, J A and Wolin, S L and Rinke, J and Pettersson, I and Mount, S M and Lerner, E A and Hinterberger, M and Gottlieb, E} } @article {49718, title = {Structure and function of small ribonucleoproteins from eukaryotic cells.}, journal = {Princess Takamatsu Symp}, volume = {12}, year = {1982}, month = {1982}, pages = {101-7}, abstract = {

Autoantibodies from patients with systemic lupus erythematosus and other related diseases have been used to identify and study small RNA-protein complexes from mammalian cells. Properties of three previously described and several new classes of small ribonucleoproteins (RNPs) are reviewed. The sequence of Drosophila U1 RNA reveals that the region proposed to pair with 5{\textquoteright} splice junctions is conserved, while that proposed to interact with 3{\textquoteright} junctions diverges; this forces some revision of the model for U1 small nuclear (sn)RNP participation in hnRNA splicing. Further characterization of the Ro and La small RNPs has shown that the Ro small cytoplasmic (sc)RNPs are a subclass of La RNPs. Both tRNA and 5S rRNA precursors are at least transiently associated with the La protein. This raises the possibility that the La protein may be an RNA polymerase III transcription factor.

}, keywords = {Antigen-Antibody Complex, Autoantibodies, HUMANS, Lupus Erythematosus, Systemic, Nucleoproteins, Ribonucleoproteins, RNA Polymerase III, Transcription, Genetic}, author = {Steitz, J A and Berg, C and Gottlieb, E and Hardin, J A and Hashimoto, C and Hendrick, J P and Hinterberger, M and Krikeles, M and Lerner, M R and Mount, S M} } @article {49721, title = {Are snRNPs involved in splicing?}, journal = {Nature}, volume = {283}, year = {1980}, month = {1980 Jan 10}, pages = {220-4}, keywords = {Animals, Base Sequence, Cell Line, Chickens, Erythrocytes, HUMANS, Liver, Lupus Erythematosus, Systemic, Molecular Weight, Nucleic Acid Precursors, Nucleoproteins, Ribonucleoproteins, RNA, Heterogeneous Nuclear, Species Specificity}, issn = {0028-0836}, author = {Lerner, M R and Boyle, J A and Mount, S M and Wolin, S L and Steitz, J A} }