Chromobox protein homolog 4(CBX4)is a component of the Polycomb group(PcG)multiprotein Polycomb repressive complexes 1(PRC1),which is participated in several processes including growth,senescence,immunity,and tissue r...Chromobox protein homolog 4(CBX4)is a component of the Polycomb group(PcG)multiprotein Polycomb repressive complexes 1(PRC1),which is participated in several processes including growth,senescence,immunity,and tissue repair.CBX4 has been shown to have diverse,even opposite functions in different types of tissue and malignancy in previous studies.展开更多
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 T...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.展开更多
基金The authors thank Dr.Kwok-Kin Wong for kindly providing the KrasG12D mice.This work was supported by the National Key R&D Program of China(2022YFA1106400 and 2020YFA0803201 to Z.W.)The National Natural Science Foundation of China(32270886 and 32070827 to Z.W.,31971111 to C.L,31900811 to W.Y.)+1 种基金The Natural Science Foundation of Guangdong Province of China(2021A1515010674 to W.Y.)Key laboratory tasks(LG202103-01-07 to Z.W.).
文摘Chromobox protein homolog 4(CBX4)is a component of the Polycomb group(PcG)multiprotein Polycomb repressive complexes 1(PRC1),which is participated in several processes including growth,senescence,immunity,and tissue repair.CBX4 has been shown to have diverse,even opposite functions in different types of tissue and malignancy in previous studies.
基金supported by the National Key R&D Program of China(Grant No.2021ZD0202500)the Shanghai Natural Science Foundation,China(Grant No.20ZR1403800)+3 种基金the National Natural Science Foundation of China(Grant Nos.31900476,82071259,31930044,and 31725012)the Shanghai Municipal Science and Technology Major Project(Grant No.2018SHZDZX01)ZJ Lab,the Shanghai Center for Brain Science and Brain-Inspired Technology,China,the Foundation of Shanghai Municipal Education Commission,China(Grant No.2019-01-07-00-07-E00062)the Collaborative Innovation Program of Shanghai Municipal Health Commission,China(Grant No.2020CXJQ01).
文摘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.
