title: Cooperative genomic alteration network reveals molecular classification across 12 major cancer types.
abstract: The accumulation of somatic genomic alterations that enables cells to gradually acquire growth advantage contributes to tumor development. This has the important implication of the widespread existence of cooperative genomic alterations in the accumulation process. Here, we proposed a computational method HCOC that simultaneously consider genetic context and downstream functional effects on cancer hallmarks to uncover somatic cooperative events in human cancers. Applying our method to 12 TCGA cancer types, we totally identified 1199 cooperative events with high heterogeneity across human cancers, and then constructed a pan-cancer cooperative alteration network. These cooperative events are associated with genomic alterations of some high-confident cancer drivers, and can trigger the dysfunction of hallmark associated pathways in a co-defect way rather than single alterations. We found that these cooperative events can be used to produce a prognostic classification that can provide complementary information with tissue-of-origin. In a further case study of glioblastoma, using 23 cooperative events identified, we stratified patients into molecularly relevant subtypes with a prognostic significance independent of the Glioma-CpG Island Methylator Phenotype (GCIMP). In summary, our method can be effectively used to discover cancer-driving cooperative events that can be valuable clinical markers for patient stratification.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Deng
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Ping
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Zhao
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Pang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Chaohan
authors.initials: C
authors.lastname: Xu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China xiaoyun@ems.hrbmu.edu.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China lixia@hrbmu.edu.cn.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D000465:Algorithms; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D056915:DNA Copy Number Variations; D053263:Gene Regulatory Networks; D014644:Genetic Variation; D023281:Genomics / Q000379:methods; D005909:Glioblastoma / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D011379:Prognosis