Identifying potential cancer driver genes by genomic data integration

被引:36
作者
Chen, Yong [1 ,2 ]
Hao, Jingjing [2 ]
Jiang, Wei [2 ]
He, Tong [3 ]
Zhang, Xuegong [2 ]
Jiang, Tao [2 ,4 ]
Jiang, Rui [2 ]
机构
[1] Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China
[2] Tsinghua Univ, TNLIST Dept Automat, Bioinformat & Bioinformat Div, MOE Key Lab, Beijing 100084, Peoples R China
[3] Cent Univ Finance & Econ, Sch Appl Math, Beijing 102206, Peoples R China
[4] Univ Calif Riverside, Dept Comp Sci & Engn, Riverside, CA 92521 USA
来源
SCIENTIFIC REPORTS | 2013年 / 3卷
基金
美国国家科学基金会; 国家高技术研究发展计划(863计划);
关键词
COPY-NUMBER ALTERATION; SYSTEMS BIOLOGY; STRUCTURAL VARIATION; DISEASE GENES; LANDSCAPE; NETWORK; EXPRESSION; PREDISPOSITION; MUTATIONS; CYTOSCAPE;
D O I
10.1038/srep03538
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cancer is a genomic disease associated with a plethora of gene mutations resulting in a loss of control over vital cellular functions. Among these mutated genes, driver genes are defined as being causally linked to oncogenesis, while passenger genes are thought to be irrelevant for cancer development. With increasing numbers of large-scale genomic datasets available, integrating these genomic data to identify driver genes from aberration regions of cancer genomes becomes an important goal of cancer genome analysis and investigations into mechanisms responsible for cancer development. A computational method, MAXDRIVER, is proposed here to identify potential driver genes on the basis of copy number aberration (CNA) regions of cancer genomes, by integrating publicly available human genomic data. MAXDRIVER employs several optimization strategies to construct a heterogeneous network, by means of combining a fused gene functional similarity network, gene-disease associations and a disease phenotypic similarity network. MAXDRIVER was validated to effectively recall known associations among genes and cancers. Previously identified as well as novel driver genes were detected by scanning CNAs of breast cancer, melanoma and liver carcinoma. Three predicted driver genes (CDKN2A, AKT1, RNF139) were found common in these three cancers by comparative analysis.
引用
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页数:9
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