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CBCB faculty Eytan Ruppin’s group publish a review paper in Molecular Systems Biology on genome-scale modeling of cancer metabolism describing current accomplishments and future challenges

Tue Jul 14, 2015
CBCB faculty Eytan Ruppin’s group has published a paper titled “Modeling cancer metabolism on a genome scale” on June 30, 2015 in the journal Molecular Systems Biology.

Cancer cells have fundamentally altered cellular metabolism that is associated with their tumorigenicity and malignancy. In addition to the widely studied Warburg effect, several new key metabolic alterations in cancer have been established over the last decade, leading to the recognition that altered tumor metabolism is one of the hallmarks of cancer. Deciphering the full scope and functional implications of the dysregulated metabolism in cancer requires both the advancement of a variety of omics measurements and the advancement of computational approaches for the analysis and contextualization of the accumulated data. Encouragingly, while the metabolic network is highly interconnected and complex, it is at the same time probably the best characterized cellular network. Following, these researchers discuss the challenges that genome‐scale modeling of cancer metabolism has been facing. They survey several recent studies demonstrating the first strides that have been done, testifying to the value of this approach in portraying a network‐level view of the cancer metabolism and in identifying novel drug targets and biomarkers. Finally, they outline a few new steps that may further advance this field.

“Modeling cancer metabolism on a genome scale” article: http://msb.embopress.org/content/11/6/817

CBCB faculty Eytan Ruppin’s group publish a paper in Molecular Systems Biology on effectiveness of drugs that reverse disease transcriptomic signatures in a mouse model of dyslipidemia

Tue Mar 03, 2015
CBCB faculty Eytan Ruppin’s group has published a paper titled “Drugs that reverse disease transcriptomic signatures are more effective in a mouse model of dyslipidemia” on March 3, 2015 in the journal Molecular Systems Biology.

High-throughputomics 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, these researchers studied a mouse model of dietinduced 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. They found 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—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’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.

“Drugs that reverse disease transcriptomic signatures are more effective in a mouse model of dyslipidemia“ article: http://msb.embopress.org/content/11/3/791

CBCB alumni win prestigious Sloan Fellowship

Wed Feb 25, 2015
Our former colleagues Michael Schatz and Cole Trapnell have been awarded the prestigious Sloan Fellowship (a full list of recipients is available here: http://www.sloan.org/fellowships/2015-sloan-research-fellows/). Many congratulations to both for this well deserved honor.

CBCB faculty Zia Khan publishes a paper in Science on the impact of regulatory variation from RNA to protein

Tue Jan 06, 2015
CBCB faculty Zia Khan and collaborators have published a paper titled “Impact of regulatory variation from RNA to protein” on December 18, 2014 in the journal Science.

In this study, Dr. Khan and collaborators mapped genetic variants that are associated with changes in gene expression, ribosome occupancy, and protein abundance in human cell lines. This is the first study to map the impact of genetic variation on three distinct regulatory layers, transcriptional, translational, and post-translational, from RNA to protein.

The study provides two main findings: (1) genetic variation that impacts gene expression tends to have attenuated or buffered affects on protein abundance (2) a new class of functional genetic variation that acts post-translationally to alter protein abundance with little affect on gene expression or protein translation. The study is the first of its kind and provides an important resource for the broader scientific community.

“Impact of regulatory variation from RNA to protein” article: http://www.sciencemag.org/content/early/2014/12/17/science.1260793.abstract

CBCB faculty Eytan Ruppin’s group publish a paper in eLife on phenotype-based cell-specific metabolic modeling

Mon Dec 01, 2014
CBCB faculty Eytan Ruppin’s group has published a paper titled “Phenotype-based cell-specific metabolic modeling reveals metabolic liabilities of cancer” on November 21, 2014 in the journal eLife.

Utilizing molecular data to derive functional physiological models tailored for specific cancer cells can facilitate the use of individually tailored therapies. To this end, they present an approach termed PRIME for generating cell-specific genome-scale metabolic models (GSMMs) based on molecular and phenotypic data. They built >280 models of normal and cancer cell-lines that successfully predict metabolic phenotypes in an individual manner. They 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, was experimentally validated and the metabolic effects of MLYCD depletion were investigated. Furthermore, they 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.

“Phenotype-based cell-specific metabolic modeling reveals metabolic liabilities of cancer” article: http://www.cs.tau.ac.il/~ruppin/prime.pdf

CBCB researchers Keith Hughitt, Lee Mendelowitz, and Joseph Paulson create an interactive tool that compares country data on women’s empowerment and stunting

Tue Nov 25, 2014
CBCB researchers Keith Hughitt, Lee Mendelowitz, and Joseph Paulson volunteered for a visualization hackathon for a D.C. non-profit called Bread for the World. They cleaned up some data and prepared a visualization of the relationship/correlation between malnutrition and women's empowerment throughout the world. Data shows that countries that empower women tend to have lower rates of stunting, which is a measure of chronic undernutrition. Their work was published in Bread for the World’s annual hunger report.

For their interactive tool that compares country data on women’s empowerment and stunting, please see: http://hungerreport.org/2015/empowerment-to-improve-nutrition/

Bread for the World’s annual hunger report: http://hungerreport.org/2015/

CBCB faculty Eytan Ruppin’s group publish a paper in Molecular Systems Biology on computational study of Warburg effect

Sep 04, 2014

CBCB faculty Eytan Ruppin's group has published a paper, led by Keren Yizhak, titled “A computational study of the Warburg effect identifies metabolic targets inhibiting cancer migration” on July 30, 2014 in the journal Molecular Systems Biology. This article presents a computational analysis of the Warburg effect, which is a key alteration characterizing the metabolism of many cancers. They show that gene knockouts reverting the Warburg effect can inhibit cancer migration and hence the likelihood of spreading metastasis. Their predictions were further tested and corroborated by their experimental collaborators from Leiden (van de Water) and Cambridge (Frezza).

“A computational study of the Warburg effect identifies metabolic targets inhibiting cancer migration” article: http://onlinelibrary.wiley.com/doi/10.15252/msb.20134993/pdf

CBCB scientists Héctor Corrada Bravo and Florin Chelaru publish a paper on Epiviz, a web-based tool for interactive visual analytics of genomics data, in Nature Methods

Thu Sep 04, 2014
CBCB faculty Héctor Corrada Bravo and CBCB doctoral student Florin Chelaru, along with undergraduate research assistants, have developed a new, web-based tool that enables researchers to quickly and easily visualize and compare large amounts of genomic information resulting from high-throughput sequencing experiments. They have described the free tool, called Epiviz, in their published paper titled “Epiviz: interactive visual analytics for functional genomics data” on Aug. 3, 2014 in the journal Nature Methods.

Next-generation sequencing has revolutionized functional genomics. These techniques are key to understanding the molecular mechanisms underlying cell function in healthy and diseased individuals and the development of diseases like cancer. Data from multiple experiments need to be integrated, but the growing number of data sets causes a thorough comparison and analysis of results to be challenging. In Corrada Bravo and Chelaru’s paper, Epiviz is shown to be capable of visualizing and analyzing DNA methylation and gene expression data in colon cancer.

“Epiviz: interactive visual analytics for functional genomics data” article: http://www.nature.com/nmeth/journal/v11/n9/full/nmeth.3038.html

For Florin Chelaru’s discussion on Epiviz and his research in bioinformatics and genomic research, please see: http://www.cs.umd.edu/article/2014/08/florin-chelaru-epiviz-research-and...

For more information, please see: http://cmns.umd.edu/news-events/features/2376

CBCB faculty Eytan Ruppin’s group publish a paper in Cell on predicting cancer-specific vulnerability

Wed Sep 03, 2014
CBCB faculty Eytan Ruppin's group has published a paper, led by Livnat Jerby, titled “Predicting Cancer-Specific Vulnerability via Data-Driven Detection of Synthetic Lethality” on Aug. 1, 2014, in the journal Cell. This article describes their development of a computational pipeline that identifies synthetic lethal interactions by analyzing large cohorts of genetic and molecular data of clinical cancer samples. With their experimental collaborators from the Beatson (Gottlieb) and the Broad (Clemons) institutes, they show that synthetic lethality networks can be used to successfully predict the response of cancer cells to various drugs and other treatments, as well as to predict clinical prognosis.

“Predicting Cancer-Specific Vulnerability via Data-Driven Detection of Synthetic Lethality” article: http://ac.els-cdn.com/S0092867414009775/1-s2.0-S0092867414009775-main.pd...

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