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.