Accurately annotate compound effects of genetic variants using a   context-sensitive framework

doi:10.1093/nar/gkx041

CORC > 北京大学 > 生命科学学院

	Accurately annotate compound effects of genetic variants using a context-sensitive framework
	Cheng, Si-Jin ; Shi, Fang-Yuan ; Liu, Huan ; Ding, Yang ; Jiang, Shuai ; Liang, Nan ; Gao, Ge
刊名	NUCLEIC ACIDS RESEARCH
	2017
关键词	CHARGE-SYNDROME MUTATION UPDATE GENOME PREDICTION EPISTASIS HUMANS
DOI	10.1093/nar/gkx041
英文摘要	In genomics, effectively identifying the biological effects of genetic variants is crucial. Current methods handle each variant independently, assuming that each variant acts in a context-free manner. However, variants within the same gene may interfere with each other, producing combinational (compound) rather than individual effects. In this work, we introduce COPE, a gene-centric variant annotation tool that integrates the entire sequential context in evaluating the functional effects of intra-genic variants. Applying COPE to the 1000 Genomes dataset, we identified numerous cases of multiple-variant compound effects that frequently led to false-positive and false-negative loss-of-function calls by conventional variant-centric tools. Specifically, 64 disease causing mutations were identified to be rescued in a specific genomic context, thus potentially contributing to the buffering effects for highly penetrant deleterious mutations. COPE is freely available for academic use at http://cope.cbi.pku.edu.cn.; National Key Research and Development Program [2016YFC0901603]; China 863 Program [2015AA020108]; International Collaboration Program for Proteome Biological Big Data and Standard System [2014DFB30030]; State Key Laboratory of Protein and Plant Gene Research; National Program for Support of Top-notch Young Professionals; State Key Laboratory of Protein and Plant Gene Research, China; SCI(E); ARTICLE; 10; 45
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/472905]
专题	生命科学学院
推荐引用方式 GB/T 7714	Cheng, Si-Jin,Shi, Fang-Yuan,Liu, Huan,et al. Accurately annotate compound effects of genetic variants using a context-sensitive framework[J]. NUCLEIC ACIDS RESEARCH,2017.
APA	Cheng, Si-Jin.,Shi, Fang-Yuan.,Liu, Huan.,Ding, Yang.,Jiang, Shuai.,...&Gao, Ge.(2017).Accurately annotate compound effects of genetic variants using a context-sensitive framework.NUCLEIC ACIDS RESEARCH.
MLA	Cheng, Si-Jin,et al."Accurately annotate compound effects of genetic variants using a context-sensitive framework".NUCLEIC ACIDS RESEARCH (2017).