{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T18:39:30Z","timestamp":1772649570271,"version":"3.50.1"},"reference-count":46,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Clin Cancer Inform"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Flow cytometry is a key diagnostic technique in hematology that provides protein information at a single-cell level. Traditionally interpreted manually in a sequence of two-dimensional plots, automated analysis techniques have grown in significance in both research and clinics improving interrater reliability and speeding up analysis. Published tools usually require a specific diagnostic setup, which hinders widespread implementation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>In this paper, we present the development of a software package and web app (diagnFlow) for the automated analysis of any in-house clinical flow cytometry data set. We exemplify the application of this classifier and its clinical benefit in lymphoma diagnosis and other settings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Routine performance for the focused diagnostic task was evaluated in a blinded one-examiner setup. Multiple customary workflows solving the task in an automated manner were designed using diagnFlow. Each workflow could improve on the performance of the manual interpretation. The most easily interpretable and computationally efficient workflow out-performed more complicated approaches and was made available as an easy-to-use web app. Same-sample wet laboratory data further elucidated the biological signal the classifier is based on. The approach made available as a web app was validated in additional data sets outperforming a competition-winning clustering-based approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>diagnFlow provides a valuable data set\u2013agnostic approach to flow cytometry data sets previously not leveraged for automatic analysis while maintaining interpretability and resource efficiency.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/cci-24-00259","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T20:00:20Z","timestamp":1761768020000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Machine Learning Designed for Any Hematologic Flow Cytometry Data Set"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0749-4360","authenticated-orcid":true,"given":"Johannes","family":"Mammen","sequence":"first","affiliation":[{"name":"Department of Medicine, Hematology, Oncology and Rheumatology, University Hospital, Heidelberg, Germany"},{"name":"European Molecular Biology Laboratory, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Calin-Petru","family":"Manta","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology, Oncology and Rheumatology, University Hospital, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Richter","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology, Oncology and Rheumatology, University Hospital, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3887-9416","authenticated-orcid":true,"given":"Nora","family":"Liebers","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology, Oncology and Rheumatology, University Hospital, Heidelberg, Germany"},{"name":"European Molecular Biology Laboratory, Heidelberg, Germany"},{"name":"Department of Hematology, Oncology and Clinical Immunology, Medical Faculty and University Hospital D\u00fcsseldorf, D\u00fcsseldorf, Germany"},{"name":"Center for Integrated Oncology Aachen Bonn Cologne D\u00fcsseldorf (CIO ABCD), D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Roider","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology, Oncology and Rheumatology, University Hospital, Heidelberg, Germany"},{"name":"European Molecular Biology Laboratory, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5868-2890","authenticated-orcid":true,"given":"Felix","family":"Czernilofsky","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology, Oncology and Rheumatology, University Hospital, Heidelberg, Germany"},{"name":"European Molecular Biology Laboratory, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Kriegsmann","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology, Oncology and Rheumatology, University Hospital, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7166-5232","authenticated-orcid":true,"given":"Carsten","family":"M\u00fcller-Tidow","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology, Oncology and Rheumatology, University Hospital, Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Hundemer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology, Oncology and Rheumatology, University Hospital, Heidelberg, Germany"},{"name":"MVZ Haematologische Diagnostik, Heppenheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sascha","family":"Dietrich","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology, Oncology and Rheumatology, University Hospital, Heidelberg, Germany"},{"name":"European Molecular Biology Laboratory, Heidelberg, Germany"},{"name":"Department of Hematology, Oncology and Clinical Immunology, Medical Faculty and University Hospital D\u00fcsseldorf, D\u00fcsseldorf, Germany"},{"name":"Center for Integrated Oncology Aachen Bonn Cologne D\u00fcsseldorf (CIO ABCD), D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16915"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2020-0261-SA"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2019.06.014"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404241"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPMMLQ67YOMGEW"},{"key":"e_1_3_8_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.160"},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.24159"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12061684"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/108.4.378"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-024-01358-2"},{"key":"e_1_3_8_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-156210"},{"key":"e_1_3_8_13_2","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2020","unstructured":"R Core Team: R: A Language and Environment for Statistical Computing. Vienna, Austria, R Core Team, 2020"},{"key":"e_1_3_8_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-24277-4"},{"key":"e_1_3_8_15_2","volume-title":"J Open Source Softw","author":"Brunson JC","year":"2017","unstructured":"Brunson JC: ggalluvial: Layered grammar for alluvial plots. J Open Source Softw 5:49, 2017"},{"key":"e_1_3_8_16_2","unstructured":"Kassambara A: ggpubr: \u2018ggplot2\u2019 Based Publication Ready Plots. R Package Version 0.6.1. 2025. https:\/\/rpkgs.datanovia.com\/ggpubr\/"},{"key":"e_1_3_8_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty441"},{"key":"e_1_3_8_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2365"},{"key":"e_1_3_8_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts300"},{"key":"e_1_3_8_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2021.100914"},{"key":"e_1_3_8_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-106"},{"key":"e_1_3_8_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-145"},{"key":"e_1_3_8_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.20531"},{"key":"e_1_3_8_24_2","doi-asserted-by":"publisher","DOI":"10.1214\/aoms\/1177730256"},{"key":"e_1_3_8_25_2","doi-asserted-by":"publisher","DOI":"10.1177\/25.7.894009"},{"key":"e_1_3_8_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0320(20000301)39:3<179::AID-CYTO2>3.0.CO;2-I"},{"key":"e_1_3_8_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.20508"},{"key":"e_1_3_8_28_2","doi-asserted-by":"publisher","DOI":"10.1109\/MSP.2017.2695801"},{"key":"e_1_3_8_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni0706-681"},{"key":"e_1_3_8_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-546"},{"key":"e_1_3_8_31_2","unstructured":"Majka M: Naivebayes: High performance implementation of the Naive Bayes algorithm. R Package Version 1.0.0. 2019. https:\/\/CRAN.R-project.org\/package=naivebayes"},{"key":"e_1_3_8_32_2","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v033.i01"},{"key":"e_1_3_8_33_2","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v106.i01"},{"key":"e_1_3_8_34_2","first-page":"18","article-title":"Classification and regression by randomForest","volume":"2","author":"Liaw A","year":"2002","unstructured":"Liaw A, Wiener M: Classification and regression by randomForest. R News 2:18-22, 2002","journal-title":"R News"},{"key":"e_1_3_8_35_2","unstructured":"Chatterjee S: fastAdaboost: A fast implementation of adaboost 2016"},{"key":"e_1_3_8_36_2","doi-asserted-by":"crossref","unstructured":"Chen T Guestrin C: XGBoost: A scalable tree boosting system in Proceedings of the 22nd ACM SIGKDD International Conference on Knowledge Discovery and Data Mining 2016 pp 785-794","DOI":"10.1145\/2939672.2939785"},{"key":"e_1_3_8_37_2","unstructured":"Mammen J: diagnFlow: Create a classifier for your clinical flow cytometry panel. https:\/\/www.dietrichlab.de\/ShinyApps\/DiagnFlow\/"},{"key":"e_1_3_8_38_2","unstructured":"WHO Classification of Tumours Editorial Board: WHO Classification of Tumours Volume 11 (ed 5). Haematolymphoid Tumours. IARC Publications 2024"},{"key":"e_1_3_8_39_2","first-page":"172","article-title":"Distribution of T-cell subsets in follicular and diffuse lymphomas of B-cell type","volume":"113","author":"Harris NL","year":"1983","unstructured":"Harris NL, Bhan AK: Distribution of T-cell subsets in follicular and diffuse lymphomas of B-cell type. Am J Pathol 113:172-180, 1983","journal-title":"Am J Pathol"},{"key":"e_1_3_8_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/0090-1229(88)90126-2"},{"key":"e_1_3_8_41_2","doi-asserted-by":"publisher","DOI":"10.5045\/br.2022.2021145"},{"key":"e_1_3_8_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05072-0"},{"key":"e_1_3_8_43_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.4.2044"},{"key":"e_1_3_8_44_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.6.4219"},{"key":"e_1_3_8_45_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1066176"},{"key":"e_1_3_8_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00428-20"},{"key":"e_1_3_8_47_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-023-05156-9"}],"container-title":["JCO Clinical Cancer Informatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/CCI-24-00259","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T20:00:22Z","timestamp":1761768022000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/CCI-24-00259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":46,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1200\/CCI-24-00259"],"URL":"https:\/\/doi.org\/10.1200\/cci-24-00259","relation":{},"ISSN":["2473-4276"],"issn-type":[{"value":"2473-4276","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2024-10-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-16","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2400259"}}