Shi-Yuan Tong , Ke Fan , Zai-Wei Zhou , Lin-Yun Liu , Shu-Qing Zhang , Yinghui Fu , Guang-Zhong Wang , Ying Zhu , Yong-Chun Yu
{"title":"mvPPT: A Highly Efficient and Sensitive Pathogenicity Prediction Tool for Missense Variants","authors":"Shi-Yuan Tong , Ke Fan , Zai-Wei Zhou , Lin-Yun Liu , Shu-Qing Zhang , Yinghui Fu , Guang-Zhong Wang , Ying Zhu , Yong-Chun Yu","doi":"10.1016/j.gpb.2022.07.005","DOIUrl":null,"url":null,"abstract":"<div><p>Next-generation sequencing technologies both boost the discovery of variants in the human genome and exacerbate the challenges of pathogenic variant identification. In this study, we developed <strong>Pathogenicity Prediction</strong> Tool for <strong>missense variants</strong> (mvPPT), a highly sensitive and accurate missense variant classifier based on gradient boosting. mvPPT adopts high-confidence training sets with a wide spectrum of variant profiles, and extracts three categories of features, including scores from existing prediction tools, frequencies (allele frequencies, amino acid frequencies, and genotype frequencies), and genomic context. Compared with established predictors, mvPPT achieves superior performance in all test sets, regardless of data source. In addition, our study also provides guidance for training set and feature selection strategies, as well as reveals highly relevant features, which may further provide biological insights into variant pathogenicity. mvPPT is freely available at <span>http://www.mvppt.club/</span><svg><path></path></svg>.</p></div>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":"21 2","pages":"Pages 414-426"},"PeriodicalIF":11.5000,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genomics, Proteomics & Bioinformatics","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1672022922000912","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Next-generation sequencing technologies both boost the discovery of variants in the human genome and exacerbate the challenges of pathogenic variant identification. In this study, we developed Pathogenicity Prediction Tool for missense variants (mvPPT), a highly sensitive and accurate missense variant classifier based on gradient boosting. mvPPT adopts high-confidence training sets with a wide spectrum of variant profiles, and extracts three categories of features, including scores from existing prediction tools, frequencies (allele frequencies, amino acid frequencies, and genotype frequencies), and genomic context. Compared with established predictors, mvPPT achieves superior performance in all test sets, regardless of data source. In addition, our study also provides guidance for training set and feature selection strategies, as well as reveals highly relevant features, which may further provide biological insights into variant pathogenicity. mvPPT is freely available at http://www.mvppt.club/.
期刊介绍:
Genomics, Proteomics and Bioinformatics (GPB) is the official journal of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China. It aims to disseminate new developments in the field of omics and bioinformatics, publish high-quality discoveries quickly, and promote open access and online publication. GPB welcomes submissions in all areas of life science, biology, and biomedicine, with a focus on large data acquisition, analysis, and curation. Manuscripts covering omics and related bioinformatics topics are particularly encouraged. GPB is indexed/abstracted by PubMed/MEDLINE, PubMed Central, Scopus, BIOSIS Previews, Chemical Abstracts, CSCD, among others.