A multiscale statistical mechanical framework integrates biophysical and genomic data to assemble cancer networks

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A multiscale statistical mechanical framework integrates biophysical and genomic data to assemble cancer networks

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Title: A multiscale statistical mechanical framework integrates biophysical and genomic data to assemble cancer networks
Author: AlQuraishi, Mohammed; Koytiger, Grigoriy; Jenney, Anne; MacBeath, Gavin; Sorger, Peter K.

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Citation: AlQuraishi, Mohammed, Grigoriy Koytiger, Anne Jenney, Gavin MacBeath, and Peter K. Sorger. 2014. “A multiscale statistical mechanical framework integrates biophysical and genomic data to assemble cancer networks.” Nature genetics 46 (12): 1363-1371. doi:10.1038/ng.3138. http://dx.doi.org/10.1038/ng.3138.
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Abstract: Functional interpretation of genomic variation is critical to understanding human disease but it remains difficult to predict the effects of specific mutations on protein interaction networks and the phenotypes they regulate. We describe an analytical framework based on multiscale statistical mechanics that integrates genomic and biophysical data to model the human SH2-phosphoprotein network in normal and cancer cells. We apply our approach to data in The Cancer Genome Atlas (TCGA) and test model predictions experimentally. We find that mutations in phosphoproteins often create new interactions but that mutations in SH2 domains result almost exclusively in loss of interactions. Some of these mutations eliminate all interactions but many cause more selective loss, thereby rewiring specific edges in highly connected subnetworks. Moreover, idiosyncratic mutations appear to be as functionally consequential as recurrent mutations. By synthesizing genomic, structural, and biochemical data our framework represents a new approach to the interpretation of genetic variation.
Published Version: doi:10.1038/ng.3138
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4244270/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:17295795
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