{"title":"PathGPS：利用 GWAS 摘要数据发现共享遗传结构。","authors":"Zijun Gao, Qingyuan Zhao, Trevor Hastie","doi":"10.1093/biomtc/ujae060","DOIUrl":null,"url":null,"abstract":"<p><p>The increasing availability and scale of biobanks and \"omic\" datasets bring new horizons for understanding biological mechanisms. PathGPS is an exploratory data analysis tool to discover genetic architectures using Genome Wide Association Studies (GWAS) summary data. PathGPS is based on a linear structural equation model where traits are regulated by both genetic and environmental pathways. PathGPS decouples the genetic and environmental components by contrasting the GWAS associations of \"signal\" genes with those of \"noise\" genes. From the estimated genetic component, PathGPS then extracts genetic pathways via principal component and factor analysis, leveraging the low-rank and sparse properties. In addition, we provide a bootstrap aggregating (\"bagging\") algorithm to improve stability under data perturbation and hyperparameter tuning. When applied to a metabolomics dataset and the UK Biobank, PathGPS confirms several known gene-trait clusters and suggests multiple new hypotheses for future investigations.</p>","PeriodicalId":8930,"journal":{"name":"Biometrics","volume":null,"pages":null},"PeriodicalIF":1.4000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247175/pdf/","citationCount":"0","resultStr":"{\"title\":\"PathGPS: discover shared genetic architecture using GWAS summary data.\",\"authors\":\"Zijun Gao, Qingyuan Zhao, Trevor Hastie\",\"doi\":\"10.1093/biomtc/ujae060\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The increasing availability and scale of biobanks and \\\"omic\\\" datasets bring new horizons for understanding biological mechanisms. PathGPS is an exploratory data analysis tool to discover genetic architectures using Genome Wide Association Studies (GWAS) summary data. PathGPS is based on a linear structural equation model where traits are regulated by both genetic and environmental pathways. PathGPS decouples the genetic and environmental components by contrasting the GWAS associations of \\\"signal\\\" genes with those of \\\"noise\\\" genes. From the estimated genetic component, PathGPS then extracts genetic pathways via principal component and factor analysis, leveraging the low-rank and sparse properties. In addition, we provide a bootstrap aggregating (\\\"bagging\\\") algorithm to improve stability under data perturbation and hyperparameter tuning. When applied to a metabolomics dataset and the UK Biobank, PathGPS confirms several known gene-trait clusters and suggests multiple new hypotheses for future investigations.</p>\",\"PeriodicalId\":8930,\"journal\":{\"name\":\"Biometrics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247175/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biometrics\",\"FirstCategoryId\":\"100\",\"ListUrlMain\":\"https://doi.org/10.1093/biomtc/ujae060\",\"RegionNum\":4,\"RegionCategory\":\"数学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biometrics","FirstCategoryId":"100","ListUrlMain":"https://doi.org/10.1093/biomtc/ujae060","RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOLOGY","Score":null,"Total":0}
PathGPS: discover shared genetic architecture using GWAS summary data.
The increasing availability and scale of biobanks and "omic" datasets bring new horizons for understanding biological mechanisms. PathGPS is an exploratory data analysis tool to discover genetic architectures using Genome Wide Association Studies (GWAS) summary data. PathGPS is based on a linear structural equation model where traits are regulated by both genetic and environmental pathways. PathGPS decouples the genetic and environmental components by contrasting the GWAS associations of "signal" genes with those of "noise" genes. From the estimated genetic component, PathGPS then extracts genetic pathways via principal component and factor analysis, leveraging the low-rank and sparse properties. In addition, we provide a bootstrap aggregating ("bagging") algorithm to improve stability under data perturbation and hyperparameter tuning. When applied to a metabolomics dataset and the UK Biobank, PathGPS confirms several known gene-trait clusters and suggests multiple new hypotheses for future investigations.
期刊介绍：
The International Biometric Society is an international society promoting the development and application of statistical and mathematical theory and methods in the biosciences, including agriculture, biomedical science and public health, ecology, environmental sciences, forestry, and allied disciplines. The Society welcomes as members statisticians, mathematicians, biological scientists, and others devoted to interdisciplinary efforts in advancing the collection and interpretation of information in the biosciences. The Society sponsors the biennial International Biometric Conference, held in sites throughout the world; through its National Groups and Regions, it also Society sponsors regional and local meetings.
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