@article {49729,
	title = {Systems-Wide Prediction of Enzyme Promiscuity Reveals a New Underground Alternative Route for Pyridoxal 5{\textquoteright}-Phosphate Production in E. coli.},
	journal = {PLoS Comput Biol},
	volume = {12},
	year = {2016},
	month = {2016 Jan},
	pages = {e1004705},
	abstract = {<p>Recent insights suggest that non-specific and/or promiscuous enzymes are common and active across life. Understanding the role of such enzymes is an important open question in biology. Here we develop a genome-wide method, PROPER, that uses a permissive PSI-BLAST approach to predict promiscuous activities of metabolic genes. Enzyme promiscuity is typically studied experimentally using multicopy suppression, in which over-expression of a promiscuous {\textquoteright}replacer{\textquoteright} gene rescues lethality caused by inactivation of a {\textquoteright}target{\textquoteright} gene. We use PROPER to predict multicopy suppression in Escherichia coli, achieving highly significant overlap with published cases (hypergeometric p = 4.4e-13). We then validate three novel predicted target-replacer gene pairs in new multicopy suppression experiments. We next go beyond PROPER and develop a network-based approach, GEM-PROPER, that integrates PROPER with genome-scale metabolic modeling to predict promiscuous replacements via alternative metabolic pathways. GEM-PROPER predicts a new indirect replacer (thiG) for an essential enzyme (pdxB) in production of pyridoxal 5{\textquoteright}-phosphate (the active form of Vitamin B6), which we validate experimentally via multicopy suppression. We perform a structural analysis of thiG to determine its potential promiscuous active site, which we validate experimentally by inactivating the pertaining residues and showing a loss of replacer activity. Thus, this study is a successful example where a computational investigation leads to a network-based identification of an indirect promiscuous replacement of a key metabolic enzyme, which would have been extremely difficult to identify directly.</p>},
	issn = {1553-7358},
	doi = {10.1371/journal.pcbi.1004705},
	author = {Oberhardt, Matthew A and Zarecki, Raphy and Reshef, Leah and Xia, Fangfang and Duran-Frigola, Miquel and Schreiber, Rachel and Henry, Christopher S and Ben-Tal, Nir and Dwyer, Daniel J and Gophna, Uri and Ruppin, Eytan}
}
@article {49592,
	title = {Phenotype-Dependent Coexpression Gene Clusters: Application to Normal and Premature Ageing},
	volume = {12},
	year = {2015},
	month = {Jan-01-2015},
	pages = {30 - 39},
	issn = {1545-5963},
	doi = {10.1109/TCBB.2014.2359446},
	url = {http://ieeexplore.ieee.org/lpdocs/epic03/wrapper.htm?arnumber=6948331http://xplorestaging.ieee.org/iel7/8857/7035191/06948331.pdf?arnumber=6948331},
	author = {Wang, Kun and Das, Avinash and Xiong, Zheng-Mei and Cao, Kan and Hannenhalli, Sridhar}
}
@conference {38586,
	title = {Identification of gene clusters with phenotype-dependent expression with application to normal and premature ageing},
	booktitle = {Proceedings of the International Conference on Bioinformatics, Computational Biology and Biomedical Informatics},
	year = {2013},
	pages = {377-383},
	publisher = {ACM},
	organization = {ACM},
	address = {Wshington DC, USA},
	author = {Kun Wang and Avinash Das and Zheng-Mei Xiong and Kan Cao and Sridhar Hannenhalli}
}
@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 {38528,
	title = {Three genomes from the phylum Acidobacteria provide insight into the lifestyles of these microorganisms in soils},
	journal = {Applied and environmental microbiologyApplied and environmental microbiology},
	volume = {75},
	year = {2009},
	note = {http://www.ncbi.nlm.nih.gov/pubmed/19201974?dopt=Abstract},
	type = {10.1128/AEM.02294-08},
	abstract = {The complete genomes of three strains from the phylum Acidobacteria were compared. Phylogenetic analysis placed them as a unique phylum. They share genomic traits with members of the Proteobacteria, the Cyanobacteria, and the Fungi. The three strains appear to be versatile heterotrophs. Genomic and culture traits indicate the use of carbon sources that span simple sugars to more complex substrates such as hemicellulose, cellulose, and chitin. The genomes encode low-specificity major facilitator superfamily transporters and high-affinity ABC transporters for sugars, suggesting that they are best suited to low-nutrient conditions. They appear capable of nitrate and nitrite reduction but not N(2) fixation or denitrification. The genomes contained numerous genes that encode siderophore receptors, but no evidence of siderophore production was found, suggesting that they may obtain iron via interaction with other microorganisms. The presence of cellulose synthesis genes and a large class of novel high-molecular-weight excreted proteins suggests potential traits for desiccation resistance, biofilm formation, and/or contribution to soil structure. Polyketide synthase and macrolide glycosylation genes suggest the production of novel antimicrobial compounds. Genes that encode a variety of novel proteins were also identified. The abundance of acidobacteria in soils worldwide and the breadth of potential carbon use by the sequenced strains suggest significant and previously unrecognized contributions to the terrestrial carbon cycle. Combining our genomic evidence with available culture traits, we postulate that cells of these isolates are long-lived, divide slowly, exhibit slow metabolic rates under low-nutrient conditions, and are well equipped to tolerate fluctuations in soil hydration.},
	keywords = {Anti-Bacterial Agents, bacteria, Biological Transport, Carbohydrate Metabolism, Cyanobacteria, DNA, Bacterial, Fungi, Genome, Bacterial, Macrolides, Molecular Sequence Data, Nitrogen, Phylogeny, Proteobacteria, Sequence Analysis, DNA, Sequence Homology, Soil Microbiology},
	author = {Ward, Naomi L. and Challacombe, Jean F. and Janssen, Peter H. and Henrissat, Bernard and Coutinho, Pedro M. and Wu, Martin and Xie, Gary and Haft, Daniel H. and Sait, Michelle and Badger, Jonathan and Barabote, Ravi D. and Bradley, Brent and Brettin, Thomas S. and Brinkac, Lauren M. and Bruce, David and Creasy, Todd and Daugherty, Sean C. and Davidsen, Tanja M. and DeBoy, Robert T. and Detter, J. Chris and Dodson, Robert J. and Durkin, A. Scott and Ganapathy, Anuradha and Gwinn-Giglio, Michelle and Han, Cliff S. and Khouri, Hoda and Kiss, Hajnalka and Kothari, Sagar P. and Madupu, Ramana and Nelson, Karen E. and Nelson, William C. and Paulsen, Ian and Penn, Kevin and Ren, Qinghu and Rosovitz, M. J. and J. Selengut and Shrivastava, Susmita and Sullivan, Steven A. and Tapia, Roxanne and Thompson, L. Sue and Watkins, Kisha L. and Yang, Qi and Yu, Chunhui and Zafar, Nikhat and Zhou, Liwei and Kuske, Cheryl R.}
}
@article {49780,
	title = {Three genomes from the phylum Acidobacteria provide insight into the lifestyles of these microorganisms in soils.},
	journal = {Appl Environ Microbiol},
	volume = {75},
	year = {2009},
	month = {2009 Apr},
	pages = {2046-56},
	abstract = {<p>The complete genomes of three strains from the phylum Acidobacteria were compared. Phylogenetic analysis placed them as a unique phylum. They share genomic traits with members of the Proteobacteria, the Cyanobacteria, and the Fungi. The three strains appear to be versatile heterotrophs. Genomic and culture traits indicate the use of carbon sources that span simple sugars to more complex substrates such as hemicellulose, cellulose, and chitin. The genomes encode low-specificity major facilitator superfamily transporters and high-affinity ABC transporters for sugars, suggesting that they are best suited to low-nutrient conditions. They appear capable of nitrate and nitrite reduction but not N(2) fixation or denitrification. The genomes contained numerous genes that encode siderophore receptors, but no evidence of siderophore production was found, suggesting that they may obtain iron via interaction with other microorganisms. The presence of cellulose synthesis genes and a large class of novel high-molecular-weight excreted proteins suggests potential traits for desiccation resistance, biofilm formation, and/or contribution to soil structure. Polyketide synthase and macrolide glycosylation genes suggest the production of novel antimicrobial compounds. Genes that encode a variety of novel proteins were also identified. The abundance of acidobacteria in soils worldwide and the breadth of potential carbon use by the sequenced strains suggest significant and previously unrecognized contributions to the terrestrial carbon cycle. Combining our genomic evidence with available culture traits, we postulate that cells of these isolates are long-lived, divide slowly, exhibit slow metabolic rates under low-nutrient conditions, and are well equipped to tolerate fluctuations in soil hydration.</p>},
	keywords = {Anti-Bacterial Agents, bacteria, Biological Transport, Carbohydrate Metabolism, Cyanobacteria, DNA, Bacterial, Fungi, Genome, Bacterial, Macrolides, Molecular Sequence Data, Nitrogen, Phylogeny, Proteobacteria, Sequence Analysis, DNA, Sequence Homology, Soil Microbiology},
	issn = {1098-5336},
	doi = {10.1128/AEM.02294-08},
	author = {Ward, Naomi L and Challacombe, Jean F and Janssen, Peter H and Henrissat, Bernard and Coutinho, Pedro M and Wu, Martin and Xie, Gary and Haft, Daniel H and Sait, Michelle and Badger, Jonathan and Barabote, Ravi D and Bradley, Brent and Brettin, Thomas S and Brinkac, Lauren M and Bruce, David and Creasy, Todd and Daugherty, Sean C and Davidsen, Tanja M and DeBoy, Robert T and Detter, J Chris and Dodson, Robert J and Durkin, A Scott and Ganapathy, Anuradha and Gwinn-Giglio, Michelle and Han, Cliff S and Khouri, Hoda and Kiss, Hajnalka and Kothari, Sagar P and Madupu, Ramana and Nelson, Karen E and Nelson, William C and Paulsen, Ian and Penn, Kevin and Ren, Qinghu and Rosovitz, M J and Selengut, Jeremy D and Shrivastava, Susmita and Sullivan, Steven A and Tapia, Roxanne and Thompson, L Sue and Watkins, Kisha L and Yang, Qi and Yu, Chunhui and Zafar, Nikhat and Zhou, Liwei and Kuske, Cheryl R}
}
@article {38165,
	title = {Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes},
	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},
	note = {http://www.ncbi.nlm.nih.gov/pubmed/15064399?dopt=Abstract},
	type = {10.1073/pnas.0307639101},
	abstract = {We present the complete 2,843,201-bp genome sequence of Treponema denticola (ATCC 35405) an oral spirochete associated with periodontal disease. Analysis of the T. denticola genome reveals factors mediating coaggregation, cell signaling, stress protection, and other competitive and cooperative measures, consistent with its pathogenic nature and lifestyle within the mixed-species environment of subgingival dental plaque. Comparisons with previously sequenced spirochete genomes revealed specific factors contributing to differences and similarities in spirochete physiology as well as pathogenic potential. The T. denticola genome is considerably larger in size than the genome of the related syphilis-causing spirochete Treponema pallidum. The differences in gene content appear to be attributable to a combination of three phenomena: genome reduction, lineage-specific expansions, and horizontal gene transfer. Genes lost due to reductive evolution appear to be largely involved in metabolism and transport, whereas some of the genes that have arisen due to lineage-specific expansions are implicated in various pathogenic interactions, and genes acquired via horizontal gene transfer are largely phage-related or of unknown function.},
	keywords = {ATP-Binding Cassette Transporters, Bacterial Proteins, Base Sequence, Borrelia burgdorferi, Genes, Bacterial, Genome, Bacterial, Leptospira interrogans, Models, Genetic, Molecular Sequence Data, Mouth, Sequence Homology, Amino Acid, Treponema, Treponema pallidum},
	author = {Seshadri, Rekha and Myers, Garry S. A. and Tettelin, Herv{\'e} and Eisen, Jonathan A. and Heidelberg, John F. and Dodson, Robert J. and Davidsen, Tanja M. and DeBoy, Robert T. and Fouts, Derrick E. and Haft, Dan H. and J. Selengut and Ren, Qinghu and Brinkac, Lauren M. and Madupu, Ramana and Kolonay, Jamie and Durkin, A. Scott and Daugherty, Sean C. and Shetty, Jyoti and Shvartsbeyn, Alla and Gebregeorgis, Elizabeth and Geer, Keita and Tsegaye, Getahun and Malek, Joel and Ayodeji, Bola and Shatsman, Sofiya and McLeod, Michael P. and Smajs, David and Howell, Jerrilyn K. and Pal, Sangita and Amin, Anita and Vashisth, Pankaj and McNeill, Thomas Z. and Xiang, Qin and Sodergren, Erica and Baca, Ernesto and Weinstock, George M. and Norris, Steven J. and Fraser, Claire M. and Paulsen, Ian T.}
}
@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.}
}
