{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:01:27Z","timestamp":1790082087676,"version":"4.0.1"},"reference-count":49,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T00:00:00Z","timestamp":1650412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1160833"],"award-info":[{"award-number":["APP1160833"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000950","name":"Cancer Council SA","doi-asserted-by":"publisher","award":["PRF1618"],"award-info":[{"award-number":["PRF1618"]}],"id":[{"id":"10.13039\/501100000950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>RNA sequencing provides a snapshot of the functional consequences of genomic lesions that drive acute lymphoblastic leukemia (ALL). The aims of this study were to elucidate diagnostic associations (via machine learning) between mRNA-seq profiles, independently verify ALL lesions and develop easy-to-interpret transcriptome-wide biomarkers for ALL subtyping in the clinical setting. A training dataset of 1279 ALL patients from six North American cohorts was used for developing machine learning models. Results were validated in 767 patients from Australia with a quality control dataset across 31 tissues from 1160 non-ALL donors. A novel batch correction method was introduced and applied to adjust for cohort differences. Out of 18,503 genes with usable expression, 11,830 (64%) were confounded by cohort effects and excluded. Six ALL subtypes (ETV6::RUNX1, KMT2A, DUX4, PAX5 P80R, TCF3::PBX1, ZNF384) that covered 32% of patients were robustly detected by mRNA-seq (positive predictive value \u2265 87%). Five other frequent subtypes (CRLF2, hypodiploid, hyperdiploid, PAX5 alterations and Ph-positive) were distinguishable in 40% of patients at lower accuracy (52% \u2264 positive predictive value \u2264 73%). Based on these findings, we introduce the Allspice R package to predict ALL subtypes and driver genes from unadjusted mRNA-seq read counts as encountered in real-world settings. Two examples of Allspice applied to previously unseen ALL patient samples with atypical lesions are included.<\/jats:p>","DOI":"10.3390\/ijms23094574","type":"journal-article","created":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T01:55:51Z","timestamp":1650506151000},"page":"4574","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Multi-Cohort Transcriptomic Subtyping of B-Cell Acute Lymphoblastic Leukemia"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7262-2656","authenticated-orcid":false,"given":"Ville-Petteri","family":"M\u00e4kinen","sequence":"first","affiliation":[{"name":"Computational and Systems Biology Program, Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia"},{"name":"Australian Centre for Precision Health, UniSA Clinical & Health Sciences, University of South Australia, Adelaide, SA 5000, Australia"},{"name":"Computational Medicine, Faculty of Medicine, University of Oulu, FI-90014 Oulu, Finland"},{"name":"Center for Life Course Health Research, Faculty of Medicine, University of Oulu, FI-90014 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5043-6943","authenticated-orcid":false,"given":"Jacqueline","family":"Rehn","sequence":"additional","affiliation":[{"name":"Blood Cancer Program, Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia"},{"name":"Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6184-0925","authenticated-orcid":false,"given":"James","family":"Breen","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"South Australian Genomics Centre, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia"},{"name":"Robinson Research Institute, University of Adelaide, Adelaide, SA 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Yeung","sequence":"additional","affiliation":[{"name":"Blood Cancer Program, Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia"},{"name":"Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Australian and New Zealand Children\u2019s Oncology Group, Clayton, VIC 3168, Australia"},{"name":"Department of Haematology, Royal Adelaide Hospital and SA Pathology, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4844-333X","authenticated-orcid":false,"given":"Deborah L.","family":"White","sequence":"additional","affiliation":[{"name":"Blood Cancer Program, Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia"},{"name":"Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Australian and New Zealand Children\u2019s Oncology Group, Clayton, VIC 3168, Australia"},{"name":"Faculty of Sciences, University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Australian Genomics Health Alliance, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e577","DOI":"10.1038\/bcj.2017.53","article-title":"Acute lymphoblastic leukemia: A comprehensive review and 2017 update","volume":"7","author":"Terwilliger","year":"2017","journal-title":"Blood Cancer J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1056\/NEJMra1400972","article-title":"Acute Lymphoblastic Leukemia in Children","volume":"373","author":"Hunger","year":"2015","journal-title":"N. 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