A Genome-wide Functional Signature Ontology Map and Applications to Natural Product Mechanism of Action Discovery

Bader, 2003, An automated method for finding molecular complexes in large protein interaction networks, BMC Bioinformatics, 4, 2, 10.1186/1471-2105-4-2 Barretina, 2012, The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity, Nature, 483, 603, 10.1038/nature11003 Carlson, 2006, Gene connectivity, function, and sequence conservation: predictions from modular yeast co-expression networks, BMC Genomics, 7, 40, 10.1186/1471-2164-7-40 Crawford, 2011, Proteasome inhibitors in cancer therapy, J. Cell Commun. Signal., 5, 101, 10.1007/s12079-011-0121-7 Elkin, 2016, Ikarugamycin: a natural product inhibitor of clathrin-mediated endocytosis, Traffic, 17, 1139, 10.1111/tra.12425 Eskiocak, 2014, The estrogen-related receptor alpha inverse agonist XCT 790 is a nanomolar mitochondrial uncoupler, Biochemistry, 53, 4839, 10.1021/bi500737n Fang, 2014, The 'dnet' approach promotes emerging research on cancer patient survival, Genome Med., 6, 64 Frey, 2007, Clustering by passing messages between data points, Science, 315, 972, 10.1126/science.1136800 Garcia, 2011, Weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAs, Nat. Struct. Mol. Biol., 18, 1139, 10.1038/nsmb.2115 Grimson, 2007, MicroRNA targeting specificity in mammals: determinants beyond seed pairing, Mol. Cell, 27, 91, 10.1016/j.molcel.2007.06.017 Hasson, 2013, High-content genome-wide RNAi screens identify regulators of parkin upstream of mitophagy, Nature, 504, 291, 10.1038/nature12748 Hughes, 2000, Functional discovery via a compendium of expression profiles, Cell, 102, 109, 10.1016/S0092-8674(00)00015-5 Jerby-Arnon, 2014, Predicting cancer-specific vulnerability via data-driven detection of synthetic lethality, Cell, 158, 1199, 10.1016/j.cell.2014.07.027 Kikugawa, 2012, PCDq: human protein complex database with quality index which summarizes different levels of evidences of protein complexes predicted from h-invitational protein-protein interactions integrative dataset, BMC Syst. Biol., 2, S7, 10.1186/1752-0509-6-S2-S7 Kim, 2013, Systematic identification of molecular subtype-selective vulnerabilities in non-small-cell lung cancer, Cell, 155, 552, 10.1016/j.cell.2013.09.041 Kim, 2016, XPO1-dependent nuclear export is a druggable vulnerability in KRAS-mutant lung cancer, Nature, 538, 114, 10.1038/nature19771 Lee, 2011, Insulin-like growth factor-binding protein-3 (IGFBP-3) blocks the effects of asthma by negatively regulating NF-kappaB signaling through IGFBP-3R-mediated activation of caspases, J. Biol. Chem., 286, 17898, 10.1074/jbc.M111.231035 Liberzon, 2011, Molecular signatures database (MSigDB) 3.0, Bioinformatics, 27, 1739, 10.1093/bioinformatics/btr260 Mcmillan, 2018, Chemistry-first approach for nomination of personalized treatment in lung cancer, Cell, 173, 864, 10.1016/j.cell.2018.03.028 Newman, 2006, Modularity and community structure in networks, Proc. Natl. Acad. Sci. U S A, 103, 8577, 10.1073/pnas.0601602103 Nichols, 2018, HORMAD1 is a negative prognostic indicator in lung adenocarcinoma and specifies resistance to oxidative and genotoxic stress, Cancer Res., 78, 6196, 10.1158/0008-5472.CAN-18-1377 Potts, 2013, Using functional signature ontology (FUSION) to identify mechanisms of action for natural products, Sci. Signal., 6, ra90, 10.1126/scisignal.2004657 Potts, 2015, Mode of action and pharmacogenomic biomarkers for exceptional responders to didemnin B, Nat. Chem. Biol., 11, 401, 10.1038/nchembio.1797 Ruepp, 2008, CORUM: the comprehensive resource of mammalian protein complexes, Nucleic Acids Res., 36, D646, 10.1093/nar/gkm936 Ruepp, 2010, CORUM: the comprehensive resource of mammalian protein complexes–2009, Nucleic Acids Res., 38, D497, 10.1093/nar/gkp914 Seashore-Ludlow, 2015, Harnessing connectivity in a large-scale small-molecule sensitivity dataset, Cancer Discov., 5, 1210, 10.1158/2159-8290.CD-15-0235 Shannon, 2003, Cytoscape: a software environment for integrated models of biomolecular interaction networks, Genome Res, 13, 2498, 10.1101/gr.1239303 Szklarczyk, 2011, The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored, Nucleic Acids Res., 39, D561, 10.1093/nar/gkq973 Vaden, 2017, FUSION-guided hypothesis development leads to the identification of N(6),N(6)-dimethyladenosine, a marine-derived AKT pathway inhibitor, Mar. Drugs, 15, 75, 10.3390/md15030075 Witkiewicz, 2015, Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets, Nat. Commun., 6, 6744, 10.1038/ncomms7744 Zhang, 2013, IGFBP-3 and TNF-alpha regulate retinal endothelial cell apoptosis, Invest. Ophthalmol. Vis. Sci., 54, 5376, 10.1167/iovs.13-12497 Zhang, 2014, IGFBP-3 inhibits TNF-alpha production and TNFR-2 signaling to protect against retinal endothelial cell apoptosis, Microvasc. Res., 95, 76, 10.1016/j.mvr.2014.07.009 Zhong, 2014, Computational detection and suppression of sequence-specific off-target phenotypes from whole genome RNAi screens, Nucleic Acids Res., 42, 8214, 10.1093/nar/gku306