Discovery of co-occurring driver pathways in cancer

doi:10.1186/1471-2105-15-271

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	Discovery of co-occurring driver pathways in cancer
	Zhang,Junhua; Wu,Ling-Yun; Zhang,Xiang-Sun; Zhang,Shihua
	2014-08-09
发表期刊	BMC Bioinformatics
ISSN	1471-2105
卷号	15 期号:1
摘要	AbstractBackgroundIt has been widely realized that pathways rather than individual genes govern the course of carcinogenesis. Therefore, discovering driver pathways is becoming an important step to understand the molecular mechanisms underlying cancer and design efficient treatments for cancer patients. Previous studies have focused mainly on observation of the alterations in cancer genomes at the individual gene or single pathway level. However, a great deal of evidence has indicated that multiple pathways often function cooperatively in carcinogenesis and other key biological processes.ResultsIn this study, an exact mathematical programming method was proposed to de novo identify co-occurring mutated driver pathways (CoMDP) in carcinogenesis without any prior information beyond mutation profiles. Two possible properties of mutations that occurred in cooperative pathways were exploited to achieve this: (1) each individual pathway has high coverage and high exclusivity; and (2) the mutations between the pair of pathways showed statistically significant co-occurrence. The efficiency of CoMDP was validated first by testing on simulated data and comparing it with a previous method. Then CoMDP was applied to several real biological data including glioblastoma, lung adenocarcinoma, and ovarian carcinoma datasets. The discovered co-occurring driver pathways were here found to be involved in several key biological processes, such as cell survival and protein synthesis. Moreover, CoMDP was modified to (1) identify an extra pathway co-occurring with a known pathway and (2) detect multiple significant co-occurring driver pathways for carcinogenesis.ConclusionsThe present method can be used to identify gene sets with more biological relevance than the ones currently used for the discovery of single driver pathways.
DOI	10.1186/1471-2105-15-271
语种	英语
WOS记录号	BMC:10.1186/1471-2105-15-271
出版者	BioMed Central
引用统计
文献类型	期刊论文
条目标识符	http://ir.amss.ac.cn/handle/2S8OKBNM/200
专题	应用数学研究所
通讯作者	Zhang,Junhua; Zhang,Shihua
作者单位	Chinese Academy of Sciences; National Center for Mathematics and Interdisciplinary Sciences, Academy of Mathematics and Systems Science
推荐引用方式 GB/T 7714	Zhang,Junhua,Wu,Ling-Yun,Zhang,Xiang-Sun,et al. Discovery of co-occurring driver pathways in cancer[J]. BMC Bioinformatics,2014,15(1).
APA	Zhang,Junhua,Wu,Ling-Yun,Zhang,Xiang-Sun,&Zhang,Shihua.(2014).Discovery of co-occurring driver pathways in cancer.BMC Bioinformatics,15(1).
MLA	Zhang,Junhua,et al."Discovery of co-occurring driver pathways in cancer".BMC Bioinformatics 15.1(2014).