{"title":"定量高通量筛选评价化学物质生物活性的统计方法","authors":"Asuka Nemoto, M. Ushijima","doi":"10.5691/JJB.38.93","DOIUrl":null,"url":null,"abstract":"Quantitative high throughput sreening (qHTS) is a technique which has originally developed as a powerful tool for drug discovery and lately is expanding its application to the neighboring field, e.g. toxicological screening test for environmental chemicals. A wide variety of in-vitro biological activity of a large amount of chemical materials can be assayed with a low cost and in a short time period. As a result of two large-scale pharmacogenomic studies being published in 2012, the reproducibility of the result of screening assay of cytotoxicity for 15 drugs in 471 cell lines was revealed to be unexpectedly low. The necessity of developments of statistical methods suitable for qHTS data were emphasized. In this review, the authors explain 3 statistical methods with applications to qHTS data, which has been proposed since 2013: 1. robust ridge regression estimators for nonlinear models in the purpose of testing bioactivity of chemicals; 2. Bayesian hierarchical dose-response modeling; 3. using weighted entropy to rank chemicals. Characteristics of each method were compared, and the prospects were presented.","PeriodicalId":365545,"journal":{"name":"Japanese journal of biometrics","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2018-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Statistical Methods for Evaluation of Bioactivity of Chemicals Using Quantitative High Throughput Screening\",\"authors\":\"Asuka Nemoto, M. Ushijima\",\"doi\":\"10.5691/JJB.38.93\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Quantitative high throughput sreening (qHTS) is a technique which has originally developed as a powerful tool for drug discovery and lately is expanding its application to the neighboring field, e.g. toxicological screening test for environmental chemicals. A wide variety of in-vitro biological activity of a large amount of chemical materials can be assayed with a low cost and in a short time period. As a result of two large-scale pharmacogenomic studies being published in 2012, the reproducibility of the result of screening assay of cytotoxicity for 15 drugs in 471 cell lines was revealed to be unexpectedly low. The necessity of developments of statistical methods suitable for qHTS data were emphasized. In this review, the authors explain 3 statistical methods with applications to qHTS data, which has been proposed since 2013: 1. robust ridge regression estimators for nonlinear models in the purpose of testing bioactivity of chemicals; 2. Bayesian hierarchical dose-response modeling; 3. using weighted entropy to rank chemicals. Characteristics of each method were compared, and the prospects were presented.\",\"PeriodicalId\":365545,\"journal\":{\"name\":\"Japanese journal of biometrics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2018-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Japanese journal of biometrics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.5691/JJB.38.93\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Japanese journal of biometrics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.5691/JJB.38.93","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Statistical Methods for Evaluation of Bioactivity of Chemicals Using Quantitative High Throughput Screening
Quantitative high throughput sreening (qHTS) is a technique which has originally developed as a powerful tool for drug discovery and lately is expanding its application to the neighboring field, e.g. toxicological screening test for environmental chemicals. A wide variety of in-vitro biological activity of a large amount of chemical materials can be assayed with a low cost and in a short time period. As a result of two large-scale pharmacogenomic studies being published in 2012, the reproducibility of the result of screening assay of cytotoxicity for 15 drugs in 471 cell lines was revealed to be unexpectedly low. The necessity of developments of statistical methods suitable for qHTS data were emphasized. In this review, the authors explain 3 statistical methods with applications to qHTS data, which has been proposed since 2013: 1. robust ridge regression estimators for nonlinear models in the purpose of testing bioactivity of chemicals; 2. Bayesian hierarchical dose-response modeling; 3. using weighted entropy to rank chemicals. Characteristics of each method were compared, and the prospects were presented.