Kim, J. W.Botvinnik, O. B.Abudayyeh, O.Birger, C.Rosenbluh, J.Shrestha, Y.Abazeed, M. E.Hammerman, P. S.DiCara, D.Konieczkowski, D. J.Johannessen, C. M.Liberzon, A.Alizad-Rahvar, A. R.Alexe, G.Aguirre, A.Ghandi, M.Greulich, H.Vazquez, F.Weir, B. A.Van Allen, E. M.Tsherniak, A.Shao, D. D.Zack, T. I.Noble, M.Getz, G.Beroukhim, R.Garraway, L. A.Ardakani, M.Romualdi, C.Sales, G.Barbie, D. A.Boehm, J. S.Hahn, W. C.Mesirov, J. P.Tamayo, P.2016-11-182016Kim, J. W., O. B. Botvinnik, O. Abudayyeh, C. Birger, J. Rosenbluh, Y. Shrestha, M. E. Abazeed, et al. 2016. “Characterizing genomic alterations in cancer by complementary functional associations.” Nature biotechnology 34 (5): 539-546. doi:10.1038/nbt.3527. http://dx.doi.org/10.1038/nbt.3527.1087-0156http://nrs.harvard.edu/urn-3:HUL.InstRepos:29408333Systematic efforts to sequence the cancer genome have identified large numbers of relevant mutations and copy number alterations in human cancers; however, elucidating their functional consequences, and their interactions to drive or maintain oncogenic states, is still a significant challenge. Here we introduce REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene-dependency of oncogenic pathways or the sensitivity to a drug treatment. We use REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes.en-USJournal Article2016-11-1810.1038/nbt.3527