{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T16:36:04Z","timestamp":1780418164000,"version":"3.54.1"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 research and innovation programme under Grant Agreement","award":["667403"],"award-info":[{"award-number":["667403"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme under Grant Agreement","award":["965193"],"award-info":[{"award-number":["965193"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme under Grant Agreement","award":["847912"],"award-info":[{"award-number":["847912"]}]},{"name":"Sigrid Jus\u00e9lius Foundation and the Cancer Foundation Finland"},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["322927"],"award-info":[{"award-number":["322927"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,28]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Motivation<\/jats:title><jats:p>RNA sequencing and other high-throughput technologies are essential in understanding complex diseases, such as cancers, but are susceptible to technical factors manifesting as patterns in the measurements. These batch patterns hinder the discovery of biologically relevant patterns. Unbiased batch effect correction in heterogeneous populations currently requires special experimental designs or phenotypic labels, which are not readily available for patient samples in existing datasets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We present POIBM, an RNA-seq batch correction method, which learns virtual reference samples directly from the data. We use a breast cancer cell line dataset to show that POIBM exceeds or matches the performance of previous methods, while being blind to the phenotypes. Further, we analyze The Cancer Genome Atlas RNA-seq data to show that batch effects plague many cancer types; POIBM effectively discovers the true replicates in stomach adenocarcinoma; and integrating the corrected data in endometrial carcinoma improves cancer subtyping.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>https:\/\/bitbucket.org\/anthakki\/poibm\/ (archived at https:\/\/doi.org\/10.5281\/zenodo.6122436).<\/jats:p><\/jats:sec><jats:sec><jats:title>Supplementary information<\/jats:title><jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/btac124","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T12:32:45Z","timestamp":1645533165000},"page":"2474-2480","source":"Crossref","is-referenced-by-count":11,"title":["POIBM: batch correction of heterogeneous RNA-seq datasets through latent sample matching"],"prefix":"10.1093","volume":"38","author":[{"given":"Susanna","family":"Holmstr\u00f6m","sequence":"first","affiliation":[{"name":"Research Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki , FI-00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7749-2694","authenticated-orcid":false,"given":"Sampsa","family":"Hautaniemi","sequence":"additional","affiliation":[{"name":"Research Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki , FI-00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8081-1588","authenticated-orcid":false,"given":"Antti","family":"H\u00e4kkinen","sequence":"additional","affiliation":[{"name":"Research Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki , FI-00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"key":"2023041402560266100_","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1186\/s12864-017-3770-y","article-title":"Pan-cancer analysis reveals technical artifacts in TCGA germline variant calls","volume":"18","author":"Buckley","year":"2017","journal-title":"BMC Genomics"},{"key":"2023041402560266100_","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.cell.2015.09.033","article-title":"Comprehensive molecular portraits of invasive lobular breast cancer","volume":"163","author":"Ciriello","year":"2015","journal-title":"Cell"},{"key":"2023041402560266100_","doi-asserted-by":"crossref","first-page":"2882","DOI":"10.1093\/bioinformatics\/btab178","article-title":"PRISM: recovering cell type specific expression profiles from individual composite RNA-seq samples","volume":"37","author":"Hakkinen","year":"2021","journal-title":"Bioinformatics"},{"key":"2023041402560266100_","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1093\/biostatistics\/kxj037","article-title":"Adjusting batch effects in microarray expression data using empirical Bayes methods","volume":"8","author":"Johnson","year":"2007","journal-title":"Biostatistics"},{"key":"2023041402560266100_","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1186\/s12859-019-3017-9","article-title":"Guide for library design and bias correction for large-scale transcriptome studies using highly multiplexed RNAseq methods","volume":"20","author":"Katayama","year":"2019","journal-title":"BMC Bioinformatics"},{"key":"2023041402560266100_","first-page":"193","article-title":"Monitoring of technical variation in quantitative high-throughput datasets","volume":"12","author":"Lauss","year":"2013","journal-title":"Cancer Inf"},{"key":"2023041402560266100_","doi-asserted-by":"crossref","first-page":"e161","DOI":"10.1093\/nar\/gku864","article-title":"svaseq: removing batch effects and other unwanted noise from sequencing data","volume":"42","author":"Leek","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2023041402560266100_","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/nrg2825","article-title":"Tackling the widespread and critical impact of batch effects in high-throughput data","volume":"11","author":"Leek","year":"2010","journal-title":"Nat. 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