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High Res

Matthew T. Weirauch, PhD

Assistant Professor, UC Department of Pediatrics

Phone: 513-803-9078

Email: matthew.weirauch@cchmc.org

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Specialties

Transcription factors; transcriptional regulation; functional genomics; genome analysis; network-based algorithms; bioinformatics

Visit the Weirauch Lab

Biography

The staggering diversity of life on our planet stems from the elegant system encoded in our genomes. A major finding of the genomic era is that a substantial proportion of the wide range of biological form and function is likely explained by differences in gene regulation (the processes governing how and when genes are utilized), as opposed to differences in the genes themselves. An important component of gene regulation is the binding of transcription factors (TFs) to genomic DNA. A typical metazoan genome contains thousands of TFs, and knowledge of their sequence binding preferences is crucial to our understanding of the “regulatory code” governing health and disease.

Two major obstacles stand in our way before we can even begin to accurately model gene regulation. First, we must gain a thorough knowledge of the sequence binding preferences of TFs. Of an estimated 165,000 TFs present in the approximately 300 sequenced eukaryotic organisms, sequence preferences are currently known for only ~2,000 (~1%). In collaboration with Tim Hughes at the University of Toronto, I have developed a joint experimental and computational approach to determine or predict binding preferences for > 55,000 eukaryotic TFs (>30%), representing an order of magnitude improvement over our current knowledge. Second, there is an ongoing controversy surrounding the optimal way to represent TF binding preferences, and how to accurately model them to predict binding to genomic sequences. To address this issue, I have recently led the largest evaluation of computational TF binding models to date, involving 20 methods developed by researchers from around the world. Together, these two studies will provide the groundwork for the future development of models of gene regulation in both normal and disease states.

Education and Training

Postdoctoral Fellow: University of Toronto (Donnelly Center for Cellular and Biomolecular Research), Toronto, Ontario, Canada.

PhD: Bioinformatics, University of California Santa Cruz, Santa Cruz, California.

BSc: Computer Science, Pennsylvania State University, University Park, PA.

Publications

View PubMed Publications

Weirauch M, Hughes T. A catalogue of eukaryotic transcription factor types, their evolutionary origin, and species distribution. Subcell Biochem. 2011;52:25-73. In: A Handbook of Transcription Factors, First Edition. Springer. Hughes, T, editor.

Weirauch M. Gene co-expression networks for the analysis of DNA microarray data. In: Applied Statistics for Network Biology: Methods in Systems Biology, First Edition. Wiley-VCH Verlag. Dehmer M, Emmert-Streib F, Graber A, Salvador A, editors. 2011.

Weirauch M, Hughes T. Dramatic changes in transcription factor binding over evolutionary time. Genome Biol. 2010 Jun 1;11(6):122.

Wang B, Kline C, Pastor D, Olson T, Frank B, Luu T, Sharma A, Robertson G, Weirauch M, Patierno S, Stuart J, Irby R, Lee N. Prostate apoptosis response protein 4 sensitizes human colon cancer cells to chemotherapeutic 5-FU through mediation of an NF kappaB and microRNA network. Mol Cancer. 2010 Apr 30;9:98.

Costanzo M, Baryshnikova A, Bellay J, Kim Y, Spear E, Sevier C, Ding H, Koh J, Toufighi K, Mostafavi S, Prinz J, St Onge R, VanderSluis B, Makhnevych T, Vizeacoumar F, Alizadeh S, Bahr S, Brost R, Chen Y, Cokol M, Deshpande R, Li Z, Lin Z, Liang W, Marback M, Paw J, San Luis B, Shuteriqi E, Tong A, van Dyk N, Wallace I, Whitney J, Weirauch M, Zhong G, Zhu H, Houry W, Brudno M, Ragibizadeh S, Papp B, Pál C, Roth F, Giaever G, Nislow C, Troyanskaya O, Bussey H, Bader G, Gingras A, Morris Q, Kim P, Kaiser C, Myers C, Andrews B, Boone C. The genetic landscape of a cell. Science. 2010 Jan 22;327(5964):425-31.

Weirauch M, Hughes T. Conserved expression without conserved regulatory sequence: the more things change, the more they stay the same. Trends Genet. 2010 Feb;26(2):66-74.

Weirauch M, Wong C, Byrne A, Stuart J. Information-based methods for predicting gene function from systematic gene knock-downs. BMC Bioinformatics. 2008 Oct 29;9:463.

Byrne A, Weirauch M, Wong V, Koeva M, Dixon S, Stuart J, Roy P. A global analysis of genetic interactions in Caenorhabditis elegans. J Biol. 2007;6(3):8.

ENCODE Project Consortium. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007 Jun 14;447(7146):799-816.

Chen C, Weirauch M, Powell C, Zambon A, Stuart J. A search engine to identify new pathway genes from expression data on multiple organisms. BMC Systems Biology. 2007 May 4;1(1):20.