Title | Accurately annotate compound effects of genetic variants using a context-sensitive framework |
Authors | Cheng, Si-Jin Shi, Fang-Yuan Liu, Huan Ding, Yang Jiang, Shuai Liang, Nan Gao, Ge |
Affiliation | Peking Univ, State Key Lab Prot & Plant Gene Res, Sch Life Sci, Ctr Bioinformat, Beijing 100871, Peoples R China. Novo Nordisk China Pharmaceut Co Ltd, 1 W Dawang Rd, Beijing 100026, Peoples R China. |
Keywords | CHARGE-SYNDROME MUTATION UPDATE GENOME PREDICTION EPISTASIS HUMANS |
Issue Date | 2017 |
Publisher | NUCLEIC ACIDS RESEARCH |
Citation | NUCLEIC ACIDS RESEARCH.2017,45(10). |
Abstract | 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. |
URI | http://hdl.handle.net/20.500.11897/472905 |
ISSN | 0305-1048 |
DOI | 10.1093/nar/gkx041 |
Indexed | SCI(E) |
Appears in Collections: | 生命科学学院 |