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Many recent efforts to analyze cancer genomes involve aggregation of mutations within reference maps of molecular pathways and protein networks. Here, we find these pathway studies are impeded by molecular interactions that are functionally irrelevant to cancer or the patient's tumor type, as these interactions diminish the contrast of driver pathways relative to individual frequently mutated genes. This problem can be addressed by creating stringent tumor-specific networks of biophysical protein interactions, identified by signatures of epistatic selection during tumor evolution. Using such an evolutionarily selected pathway (ESP) map, we analyze the major cancer genome atlases to derive a hierarchical classification of tumor subtypes linked to characteristic mutated pathways. These pathways are clinically prognostic and predictive, including the TP53-AXIN-ARHGEF17 combination in liver and CYLC2-STK11-STK11IP in lung cancer, which we validate in independent cohorts. This ESP framework substantially improves the definition of cancer pathways and subtypes from tumor genome data.
Pubmed ID: 30297789
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Multi paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.
View all literature mentionsWikipedia is a free, web-based, collaborative, multilingual encyclopedia project supported by the non-profit Wikimedia Foundation. Its 19 million articles (over 3.6 million in English) have been written collaboratively by volunteers around the world, and almost all of its articles can be edited by anyone with access to the site. As of July 2011, there were editions of Wikipedia in 282 languages. Wikipedia was launched in 2001 by Jimmy Wales and Larry Sanger and has become the largest and most popular general reference work on the Internet, ranking around seventh among all websites on Alexa and having 365 million readers. The name Wikipedia was coined by Larry Sanger and is a combination of wiki (a technology for creating collaborative websites, from the Hawaiian word wiki, meaning quick) and encyclopedia. Wikipedia''s departure from the expert-driven style of encyclopedia building and the large presence of unacademic content has been noted several times. Some have noted the importance of Wikipedia not only as an encyclopedic reference but also as a frequently updated news resource because of how quickly articles about recent events appear. Although the policies of Wikipedia strongly espouse verifiability and a neutral point of view, critics of Wikipedia accuse it of systemic bias and inconsistencies (including undue weight given to popular culture), and allege that it favors consensus over credentials in its editorial processes. Its reliability and accuracy are also targeted. A 2005 investigation in Nature showed that the science articles they compared came close to the level of accuracy of Encyclopedia Britannica and had a similar rate of serious errors.
View all literature mentionsDatabase of known and predicted protein interactions. The interactions include direct (physical) and indirect (functional) associations and are derived from four sources: Genomic Context, High-throughput experiments, (Conserved) Coexpression, and previous knowledge. STRING quantitatively integrates interaction data from these sources for a large number of organisms, and transfers information between these organisms where applicable. The database currently covers 5''214''234 proteins from 1133 organisms. (2013)
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