{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:58:18Z","timestamp":1788998298974,"version":"build-2803163510"},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,12,22]],"date-time":"2024-12-22T00:00:00Z","timestamp":1734825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013373","name":"NIHR Oxford Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["P2SKP3_168322\/1"],"award-info":[{"award-number":["P2SKP3_168322\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["P2SKP3_168322\/2"],"award-info":[{"award-number":["P2SKP3_168322\/2"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Tumour content plays a pivotal role in directing the bioinformatic analysis of molecular profiles such as copy number variation (CNV). In clinical application, tumour purity estimation (TPE) is achieved either through visual pathological review [conventional pathology (CP)] or the deconvolution of molecular data. While CP provides a direct measurement, it demonstrates modest reproducibility and lacks standardisation. Conversely, deconvolution methods offer an indirect assessment with uncertain accuracy, underscoring the necessity for innovative approaches. SoftCTM is an open\u2010source, multiorgan deep\u2010learning (DL) model for the detection of tumour and non\u2010tumour cells in H&amp;E\u2010stained slides, developed within the Overlapped Cell on Tissue Dataset for Histopathology (OCELOT) Challenge 2023. Here, using three large multicentre colorectal cancer (CRC) cohorts (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20091,097 patients) with digital pathology and multi\u2010omic data, we compare the utility and accuracy of TPE with SoftCTM versus CP and bioinformatic deconvolution methods (RNA expression, DNA methylation) for downstream molecular analysis, including CNV profiling. SoftCTM showed technical repeatability when applied twice on the same slide (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20091.0) and excellent correlations in paired H&amp;E slides (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009&gt;\u20090.9). TPEs profiled by SoftCTM correlated highly with RNA expression (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.59) and DNA methylation (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.40), while TPEs by CP showed a lower correlation with RNA expression (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.41) and DNA methylation (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.29). We show that CP and deconvolution methods respectively underestimate and overestimate tumour content compared to SoftCTM, resulting in 6\u201313% differing CNV calls. In summary, TPE with SoftCTM enables reproducibility, automation, and standardisation at single\u2010cell resolution. SoftCTM estimates (\n                    <jats:italic>M<\/jats:italic>\n                    \u2009=\u200958.9%, SD \u00b116.3%) reconcile the overestimation by molecular data extrapolation (RNA expression:\n                    <jats:italic>M<\/jats:italic>\n                    \u2009=\u200979.2%, SD \u00b110.5, DNA methylation:\n                    <jats:italic>M<\/jats:italic>\n                    \u2009=\u200962.7%, SD \u00b111.8%) and underestimation by CP (\n                    <jats:italic>M<\/jats:italic>\n                    \u2009=\u200935.9%, SD \u00b113.1%), providing a more reliable middle ground. A fully integrated computational pathology solution could therefore be used to improve downstream molecular analyses for research and clinics. \u00a9 2024 The Author(s).\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6376","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:47:39Z","timestamp":1734914859000},"page":"184-197","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Tumour purity assessment with deep learning in colorectal cancer and impact on molecular analysis"],"prefix":"10.1002","volume":"265","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6703-9368","authenticated-orcid":false,"given":"Lydia A","family":"Schoenpflug","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Pathology University Hospital and University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aikaterini","family":"Chatzipli","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute  Hinxton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Korsuk","family":"Sirinukunwattana","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering (IBME), Department of Engineering Science, Old Road Campus Research Building University of Oxford  Oxford UK"},{"name":"Li Ka Shing Centre for Health Information and Discovery Big Data Institute, University of Oxford  Oxford UK"},{"name":"Oxford NIHR Biomedical Research Centre Oxford University Hospitals Trust  Oxford UK"},{"name":"Ground Truth Labs Ltd  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Richman","sequence":"additional","affiliation":[{"name":"Department of Pathology and Tumour Biology Leeds Institute of Cancer and Pathology  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8154-6253","authenticated-orcid":false,"given":"Andrew","family":"Blake","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Robineau","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten D","family":"Mertz","sequence":"additional","affiliation":[{"name":"Cantonal Hospital Baselland Institute of Pathology  Liestal Switzerland"},{"name":"Institute of Medical Genetics and Pathology University Hospital Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4905-8233","authenticated-orcid":false,"given":"Clare","family":"Verrill","sequence":"additional","affiliation":[{"name":"Li Ka Shing Centre for Health Information and Discovery Big Data Institute, University of Oxford  Oxford UK"},{"name":"Department of Cellular Pathology Oxford University Hospitals NHS Foundation Trust  Oxford UK"},{"name":"Nuffield Department of Surgical Sciences and NIHR Oxford Biomedical Research Centre University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1476-6982","authenticated-orcid":false,"given":"Simon J","family":"Leedham","sequence":"additional","affiliation":[{"name":"Gastrointestinal Stem\u2010cell Biology Laboratory, Oxford Centre for Cancer Gene Research, Wellcome Trust Centre for Human Genetics University of Oxford  Oxford UK"},{"name":"Translational Gastroenterology Unit, Experimental Medicine Division, Nuffield Department of Clinical Medicine John Radcliffe Hospital  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Hardy","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute  Hinxton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celina","family":"Whalley","sequence":"additional","affiliation":[{"name":"Institute of Cancer and Genomic Science University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keara","family":"Redmond","sequence":"additional","affiliation":[{"name":"The Patrick G Johnston Centre for Cancer Research Queens University  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9160-283X","authenticated-orcid":false,"given":"Philip","family":"Dunne","sequence":"additional","affiliation":[{"name":"The Patrick G Johnston Centre for Cancer Research Queens University  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Walker","sequence":"additional","affiliation":[{"name":"The Patrick G Johnston Centre for Cancer Research Queens University  Belfast UK"},{"name":"Almac Diagnostics  Craigavon UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0784-2967","authenticated-orcid":false,"given":"Andrew D","family":"Beggs","sequence":"additional","affiliation":[{"name":"Institute of Cancer and Genomic Science University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ultan","family":"McDermott","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute  Hinxton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme I","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Medical Sciences and Nutrition University of Aberdeen  Aberdeen UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie M","family":"Samuel","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology Aberdeen Royal Infirmary, NHS GRAMPIAN  Aberdeen UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Seymour","sequence":"additional","affiliation":[{"name":"Department of Pathology and Tumour Biology Leeds Institute of Cancer and Pathology  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3597-5444","authenticated-orcid":false,"given":"Philip","family":"Quirke","sequence":"additional","affiliation":[{"name":"Department of Pathology and Tumour Biology Leeds Institute of Cancer and Pathology  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"S:CORT consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Rittscher","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering (IBME), Department of Engineering Science, Old Road Campus Research Building University of Oxford  Oxford UK"},{"name":"Li Ka Shing Centre for Health Information and Discovery Big Data Institute, University of Oxford  Oxford UK"},{"name":"Oxford NIHR Biomedical Research Centre Oxford University Hospitals Trust  Oxford UK"},{"name":"Ground Truth Labs Ltd  Oxford UK"},{"name":"Nuffield Department of Medicine Ludwig Institute for Cancer Research, University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Maughan","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Oxford  Oxford UK"},{"name":"University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enric","family":"Domingo","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor H","family":"Koelzer","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Pathology University Hospital and University of Zurich  Zurich Switzerland"},{"name":"Department of Oncology University of Oxford  Oxford UK"},{"name":"Institute of Medical Genetics and Pathology University Hospital Basel  Basel Switzerland"},{"name":"Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-1102"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.4132\/jptm.2017.03.14"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.4391"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/PO.20.00016"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05570-1"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2203"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAI.0000000000000684"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1990.420"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2015.208"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9971"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61087-3"},{"key":"e_1_2_8_13_1","first-page":"3","article-title":"Exploration of molecular signalling underpinning the DNA damage response deficiency (DDRD) assay in colorectal cancer; data from the S:CORT consortium (stratification in COlorRecTal cancer)","volume":"121","author":"Malla S","year":"2019","journal-title":"Br J Cancer"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1507"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-319866"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-0985-5"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-55088-1_10"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1109\/CVPR52729.2023.02289"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2019-4446"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3612"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2018.02.003"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-1143-5"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004873"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3967"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0686-2"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.21105\/joss.01026"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1604033"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-23175-9_4"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13891"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2013.134"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-016-2042-6"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-024-03794-9"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr-20-1168"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.14779"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2023.100335"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.patter.2021.100399"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40291-014-0091-6"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2019.09.081"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr-20-591"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2012-0561-CP"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20030-5"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2589-7500(21)00232-6"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104067"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1117\/1.JMI.8.3.034501"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-022-00252-0"},{"key":"e_1_2_8_46_1","first-page":"1137","article-title":"Breast cancer histopathology image analysis pipeline for tumor purity estimation","volume":"2017","author":"Azimi V","year":"2017","journal-title":"Proc IEEE Int Symp Biomed Imaging"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.media.2019.101563"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1089\/bio.2020.0105"},{"key":"e_1_2_8_49_1","volume-title":"Developing a Machine Learning Model for Tumor Cell Quantification in Standard Histology Images of Lung Cancer","author":"Kristoffersen S","year":"2023"},{"key":"e_1_2_8_50_1","unstructured":"Onermustafaumit.Spatially Resolved Tumor Purity Maps (SRTPMs) [Computer Software].2021. Available from:https:\/\/github.com\/onermustafaumit\/SRTPMs\/tree\/v1.0.0."},{"key":"e_1_2_8_51_1","unstructured":"BrendelM.wsPurity [Computer Software].2022. Available from:https:\/\/github.com\/ih-lab\/wsPurity."},{"key":"e_1_2_8_52_1","unstructured":"NoorbakhshJ.HistCNN [Computer Software].2020. Available from:https:\/\/github.com\/javadnoorb\/HistCNN."},{"key":"e_1_2_8_53_1","unstructured":"SuA.HEMnet [Computer Software].2022. Available from:https:\/\/github.com\/BiomedicalMachineLearning\/HEMnet."},{"key":"e_1_2_8_54_1","unstructured":"GrahamS.HoVer\u2010net [Computer Software].2019. Available from:https:\/\/github.com\/simongraham\/hovernet_inference."},{"key":"e_1_2_8_55_1","unstructured":"L'ImperioV CazzanigaG.QuANTUM [Computer Software].2024. Available from:https:\/\/github.com\/Gizmopath\/QuANTUM."},{"key":"e_1_2_8_56_1","unstructured":"SchoenpflugLA.SoftCTM [Computer Software].2023. Available from:https:\/\/github.com\/lely475\/SoftCTM."}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.6376","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T16:45:53Z","timestamp":1761065153000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.6376"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,22]]},"references-count":55,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/path.6376"],"URL":"https:\/\/doi.org\/10.1002\/path.6376","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,22]]},"assertion":[{"value":"2024-05-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}