{"title":"在多表型关联研究中优先考虑易感稀有变异的加权选择概率及其在大豆遗传数据集中的应用。","authors":"Xianglong Liang, Hokeun Sun","doi":"10.1089/cmb.2022.0487","DOIUrl":null,"url":null,"abstract":"<p><p>Rare variant association studies with multiple traits or diseases have drawn a lot of attention since association signals of rare variants can be boosted if more than one phenotype outcome is associated with the same rare variants. Most of the existing statistical methods to identify rare variants associated with multiple phenotypes are based on a group test, where a pre-specified genetic region is tested one at a time. However, these methods are not designed to locate susceptible rare variants within the genetic region. In this article, we propose new statistical methods to prioritize rare variants within a genetic region when a group test for the genetic region identifies a statistical association with multiple phenotypes. It computes the weighted selection probability (WSP) of individual rare variants and ranks them from largest to smallest according to their WSP. In simulation studies, we demonstrated that the proposed method outperforms other statistical methods in terms of true positive selection, when multiple phenotypes are correlated with each other. We also applied it to our soybean single nucleotide polymorphism (SNP) data with 13 highly correlated amino acids, where we identified some potentially susceptible rare variants in chromosome 19.</p>","PeriodicalId":15526,"journal":{"name":"Journal of Computational Biology","volume":null,"pages":null},"PeriodicalIF":1.4000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Weighted Selection Probability to Prioritize Susceptible Rare Variants in Multi-Phenotype Association Studies with Application to a Soybean Genetic Data Set.\",\"authors\":\"Xianglong Liang, Hokeun Sun\",\"doi\":\"10.1089/cmb.2022.0487\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Rare variant association studies with multiple traits or diseases have drawn a lot of attention since association signals of rare variants can be boosted if more than one phenotype outcome is associated with the same rare variants. Most of the existing statistical methods to identify rare variants associated with multiple phenotypes are based on a group test, where a pre-specified genetic region is tested one at a time. However, these methods are not designed to locate susceptible rare variants within the genetic region. In this article, we propose new statistical methods to prioritize rare variants within a genetic region when a group test for the genetic region identifies a statistical association with multiple phenotypes. It computes the weighted selection probability (WSP) of individual rare variants and ranks them from largest to smallest according to their WSP. In simulation studies, we demonstrated that the proposed method outperforms other statistical methods in terms of true positive selection, when multiple phenotypes are correlated with each other. We also applied it to our soybean single nucleotide polymorphism (SNP) data with 13 highly correlated amino acids, where we identified some potentially susceptible rare variants in chromosome 19.</p>\",\"PeriodicalId\":15526,\"journal\":{\"name\":\"Journal of Computational Biology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2023-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Computational Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1089/cmb.2022.0487\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Computational Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1089/cmb.2022.0487","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Weighted Selection Probability to Prioritize Susceptible Rare Variants in Multi-Phenotype Association Studies with Application to a Soybean Genetic Data Set.
Rare variant association studies with multiple traits or diseases have drawn a lot of attention since association signals of rare variants can be boosted if more than one phenotype outcome is associated with the same rare variants. Most of the existing statistical methods to identify rare variants associated with multiple phenotypes are based on a group test, where a pre-specified genetic region is tested one at a time. However, these methods are not designed to locate susceptible rare variants within the genetic region. In this article, we propose new statistical methods to prioritize rare variants within a genetic region when a group test for the genetic region identifies a statistical association with multiple phenotypes. It computes the weighted selection probability (WSP) of individual rare variants and ranks them from largest to smallest according to their WSP. In simulation studies, we demonstrated that the proposed method outperforms other statistical methods in terms of true positive selection, when multiple phenotypes are correlated with each other. We also applied it to our soybean single nucleotide polymorphism (SNP) data with 13 highly correlated amino acids, where we identified some potentially susceptible rare variants in chromosome 19.
期刊介绍:
Journal of Computational Biology is the leading peer-reviewed journal in computational biology and bioinformatics, publishing in-depth statistical, mathematical, and computational analysis of methods, as well as their practical impact. Available only online, this is an essential journal for scientists and students who want to keep abreast of developments in bioinformatics.
Journal of Computational Biology coverage includes:
-Genomics
-Mathematical modeling and simulation
-Distributed and parallel biological computing
-Designing biological databases
-Pattern matching and pattern detection
-Linking disparate databases and data
-New tools for computational biology
-Relational and object-oriented database technology for bioinformatics
-Biological expert system design and use
-Reasoning by analogy, hypothesis formation, and testing by machine
-Management of biological databases