<html><head><style type='text/css'>p { margin: 0; }</style></head><body><div style='font-family: arial,helvetica,sans-serif; font-size: 10pt; color: #000000'>Borislav Hristov will present his research seminar/general exam on Tuesday May 6 at 10AM <br>in Room 402. The members of his committee are: Mona Singh (advisor), Olga Troyanskaya, <br>and Tom Funkhouser. Everyone is invited to attend his talk, and those faculty wishing to remain <br>for the oral exam following are welcome to do so. His abstract and reading list follow below.<br><br><hr id="zwchr"><span><p style="line-height:1.15;margin-top:0pt;margin-bottom:0pt"><span style="font-size:15px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap"></span></p><p dir="ltr" style="line-height:1.15;margin-top:0pt;margin-bottom:0pt">
<span style="font-size:15px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap"><br></span></p><p dir="ltr" style="line-height:1.15;margin-top:0pt;margin-bottom:0pt"><span style="font-size:15px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap">Abstract:</span></p>
<br><p dir="ltr" style="line-height:1.15;margin-top:0pt;margin-bottom:0pt"><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap">The improvement and the decreased cost of next generation DNA sequencing have enabled genome wide measurements in large numbers of individuals. This allows researchers to compare the genome variations in both healthy and sick individuals in order to help uncover the genetic underpinnings of human disease. However, complex diseases are caused by a combination of genetic perturbations- often the same phenotypic outcome (a disease case) can result from a different set of possible mutations, possibly in different loci. Cancer is a disease which exhibits such a great genetic heterogeneity. This makes studying it and identifying causal variants extremely difficult. </span></p>
<br><p dir="ltr" style="line-height:1.15;margin-top:0pt;margin-bottom:0pt"><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap">We combine knowledge of biological interactions with genome sequencing data from The Cancer Genome Atlas to perform an integrated analysis of several types of cancer. Our hypothesis is that even though different patients could have entirely disjoint sets of somatic variants, these variants disturb similar cell processes and hence are closely connected in the biological network. We phrase the problem precisely in mathematical terms and devise an efficient greedy heuristic to solve it. We use a robust framework of cross validation tests to demonstrate the soundness of our approach. We are able to recover well known cancer genes as well as to highlight possible new ones. We show that our method yields both efficient and biologically relevant results.</span></p>
<br><br><p dir="ltr" style="line-height:1.15;margin-top:0pt;margin-bottom:0pt"><span style="vertical-align:baseline;font-size:15px;white-space:pre-wrap;background-color:transparent;font-family:Arial">Reading List:</span></p>
<br><p dir="ltr" style="line-height:1.15;margin-top:0pt;margin-bottom:0pt"><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap">Yona, Golan. </span><span style="font-size:13px;font-family:Arial;font-style:italic;vertical-align:baseline;white-space:pre-wrap">Introduction to Computational Proteomics</span><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap">. CRC Press, 2011. Chapters: 1-7, 10, 13.2</span></p>
<br><p dir="ltr" style="line-height:1.15;margin-top:0pt;margin-bottom:0pt"><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap">Dand, Nick, et al. "BioGranat-IG: a network analysis tool to suggest mechanisms of genetic heterogeneity from exome-sequencing data."</span><span style="font-size:13px;font-family:Arial;font-style:italic;vertical-align:baseline;white-space:pre-wrap">Bioinformatics</span><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap"> 29.6 (2013): 733-741.</span></p>
<br><p dir="ltr" style="line-height:1.15;margin-top:0pt;margin-bottom:0pt"><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap">Vandin, Fabio, Eli Upfal, and Benjamin J. Raphael. "Algorithms for detecting significantly mutated pathways in cancer." </span><span style="font-size:13px;font-family:Arial;font-style:italic;vertical-align:baseline;white-space:pre-wrap">Journal of Computational Biology </span><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap">18.3 (2011): 507-522.</span></p>
<br><p dir="ltr" style="line-height:1.15;margin-top:0pt;margin-bottom:0pt"><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap">Ulitsky, Igor, et al. "DEGAS: de novo discovery of dysregulated pathways in human diseases." </span><span style="font-size:13px;font-family:Arial;font-style:italic;vertical-align:baseline;white-space:pre-wrap">PLoS One</span><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap"> 5.10 (2010): e13367.</span></p>
<br><p dir="ltr" style="line-height:1.15;margin-top:0pt;margin-bottom:0pt"><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap">Navlakha, Saket, and Carl Kingsford. "The power of protein interaction networks for associating genes with diseases." </span><span style="font-size:13px;font-family:Arial;font-style:italic;vertical-align:baseline;white-space:pre-wrap">Bioinformatics</span><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap"> 26.8 (2010): 1057-1063. </span></p>
<br><p dir="ltr" style="line-height:1.15;margin-top:0pt;margin-bottom:0pt"><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap">Wang, Peggy I., and Edward M. Marcotte. "It's the machine that matters: Predicting gene function and phenotype from protein networks." </span><span style="font-size:13px;font-family:Arial;font-style:italic;vertical-align:baseline;white-space:pre-wrap">Journal of proteomics</span><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap"> 73.11 (2010): 2277-2289.</span></p>
<br><p dir="ltr" style="line-height:1.15;margin-top:0pt;margin-bottom:0pt"><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap">Gosline, Sara JC, et al. "SAMNet: a network-based approach to integrate multi-dimensional high throughput datasets." </span><span style="font-size:13px;font-family:Arial;font-style:italic;vertical-align:baseline;white-space:pre-wrap">Integrative Biology</span><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap"> 4.11 (2012): 1415-1427.</span></p>
<br><p dir="ltr" style="line-height:1.15;margin-top:0pt;margin-bottom:0pt"><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap">Lee, Insuk, et al. "Prioritizing candidate disease genes by network-based boosting of genome-wide association data." </span><span style="font-size:13px;font-family:Arial;font-style:italic;vertical-align:baseline;white-space:pre-wrap">Genome research</span><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap"> 21.7 (2011): 1109-1121.</span></p>
<br><p dir="ltr" style="line-height:1.15;margin-top:0pt;margin-bottom:0pt"><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap">Hofree, Matan, et al. "Network-based stratification of tumor mutations." </span><span style="font-size:13px;font-family:Arial;font-style:italic;vertical-align:baseline;white-space:pre-wrap">Nature methods</span><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap"> (2013).</span></p>
<br><p dir="ltr" style="line-height:1.15;margin-top:0pt;margin-bottom:0pt"><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap">Jiang, Peng, and Mona Singh. "SPICi: a fast clustering algorithm for large biological networks." </span><span style="font-size:13px;font-family:Arial;font-style:italic;vertical-align:baseline;white-space:pre-wrap">Bioinformatics</span><span style="font-size:13px;font-family:Arial;vertical-align:baseline;white-space:pre-wrap"> 26.8 (2010): 1105-1111.</span></p>
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