Abstract
AbstractExome sequencing is now mainstream in clinical practice. However, identification of pathogenic Mendelian variants remains time-consuming, in part, because the limited accuracy of current computational prediction methods requires manual classification by experts. Here we introduce CAPICE, a new machine-learning-based method for prioritizing pathogenic variants, including SNVs and short InDels. CAPICE outperforms the best general (CADD, GAVIN) and consequence-type-specific (REVEL, ClinPred) computational prediction methods, for both rare and ultra-rare variants. CAPICE is easily added to diagnostic pipelines as pre-computed score file or command-line software, or using online MOLGENIS web service with API. Download CAPICE for free and open-source (LGPLv3) at https://github.com/molgenis/capice.
Funder
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Publisher
Springer Science and Business Media LLC
Subject
Genetics(clinical),Genetics,Molecular Biology,Molecular Medicine
Reference51 articles.
1. Boudellioua I, Mahamad Razali RB, Kulmanov M, Hashish Y, Bajic VB, Goncalves-Serra E, et al. Semantic prioritization of novel causative genomic variants. PLoS Comput Biol. 2017;13(4):e1005500 [cited 2018 May 3] Available from: http://www.ncbi.nlm.nih.gov/pubmed/28414800.
2. Lionel AC, Costain G, Monfared N, Walker S, Reuter MS, Hosseini SM, et al. Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test. Genet Med. 2018;20(4):435–43. [cited 2018 May 9] Available from: http://www.nature.com/doifinder/10.1038/gim.2017.119.
3. Clark MM, Hildreth A, Batalov S, Ding Y, Chowdhury S, Watkins K, et al. Diagnosis of genetic diseases in seriously ill children by rapid whole-genome sequencing and automated phenotyping and interpretation. Sci Transl Med. 2019;11(489):eaat6177. [cited 2019 Oct 2] Available from: http://www.ncbi.nlm.nih.gov/pubmed/31019026.
4. Sawyer SL, Hartley T, Dyment DA, Beaulieu CL, Schwartzentruber J, Smith A, et al. Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care. Clin Genet. 2016;89(3):275–84. [cited 2019 Oct 2] Available from: http://www.ncbi.nlm.nih.gov/pubmed/26283276.
5. Trujillano D, Bertoli-Avella AM, Kumar Kandaswamy K, Weiss ME, Köster J, Marais A, et al. Clinical exome sequencing: results from 2819 samples reflecting 1000 families. Eur J Hum Genet. 2017;25(2):176–82. [cited 2018 Nov 30] Available from: http://www.nature.com/articles/ejhg2016146.
Cited by
28 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献