MSEA: detection and quantification of mutation hotspots through mutation set enrichment analysis

被引：49

作者：

Jia, Peilin ^{[1
,2
]}

Wang, Quan ^{[1
]}

Chen, Qingxia ^{[1
,3
]}

Hutchinson, Katherine E. ^{[4
]}

Pao, William ^{[4
,5
]}

Zhao, Zhongming ^{[1
,2
,4
,6
]}

机构：

[1] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37203 USA

[2] Vanderbilt Univ, Med Ctr, Ctr Quantitat Sci, Nashville, TN 37232 USA

[3] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37232 USA

[4] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37232 USA

[5] Vanderbilt Univ, Sch Med, Dept Med, Div Hematol Oncol, Nashville, TN 37232 USA

[6] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA

来源：

GENOME BIOLOGY | 2014年 / 15卷 / 10期

基金：

美国国家卫生研究院;

关键词：

DRIVER MUTATIONS; SOMATIC MUTATIONS; CANCER DRIVERS; TUMOR TYPES; MISSENSE MUTATIONS; FUNCTIONAL IMPACT; GENETIC-VARIANTS; LANDSCAPE; GENOMES; DISCOVERY;

D O I：

10.1186/s13059-014-0489-9

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Many cancer genes form mutation hotspots that disrupt their functional domains or active sites, leading to gain- or loss-of-function. We propose a mutation set enrichment analysis (MSEA) implemented by two novel methods, MSEA-clust and MSEA-domain, to predict cancer genes based on mutation hotspot patterns. MSEA methods are evaluated by both simulated and real cancer data. We find approximately 51% of the eligible known cancer genes form detectable mutation hotspots. Application of MSEA in eight cancers reveals a total of 82 genes with mutation hotspots, including well-studied cancer genes, known cancer genes re-found in new cancer types, and novel cancer genes.

引用

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