Dana Peer, Columbia University, USA

A network approach to understanding cancer
Networks underlying the functioning of the cell in health and disease. Genetic mutations in cancer cause these fine tuned regulatory networks to go awry. Each cancer is unique and there is a plethora of ways by which aberrations can disrupt in normal regulation and result in malignant phenotypes. Our class will study heterogeneity of cancer from a disease perspective. We will begin by demonstrating data driven approaches to uncover how genetic variation might alter regulatory networks and subsequently phenotypes such as drug response, using yeast as a model system, computational techniques learned will include module networks and regularized regression. We will then learn how these approaches can be used to integrate the rapidly accumulating data collected from cancer samples (The Cancer Genome Atlas and International Cancer Genome Consortium) to map the mutations driving cancer pathogenesis. Finally we will give examples demonstrating how single cell data can be explored to uncover heterogeneity not only between cancers, but also within a cancer.

Literature
Pe'er D., Hacohen N., Principles and Strategies for Developing Network Models in Cancer. Cell. 144(6):864-73, March 2011

Lee, S., Pe’er, D. Dudley, A., Church, G., and Koller, D .“Identifying Regulatory Mechanisms and their Individual Variation Reveals Key Role of Chromatin Modification”, Proceedings of the National Academy of Science, 19;103(38):14062-7, Sep 2006.

Chen, BJ., Causton, HC., Goddard, NL., Perlstein, EO. and Pe’er, D. “Harnessing gene expression to identify the genetic basis of drug resistance”, Molecular Systems Biology, 2009;5:310, Oct 2009.

Akavia UD., Litvin O., Kim J., Sanchez-Garcia F., Kotliar D., Causton, HC., Pochanard P., Mozes E., Garraway LA., Pe'er D. “An Integrated Approach to Uncover Drivers of Cancer”, Cell, 10;143(6):1005-17, Dec 2010.

Cancer Genome Atlas Research Network. (2008). Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455, 1061–1068.