{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T13:18:51Z","timestamp":1777987131789,"version":"3.51.4"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Primary immunodeficiencies (PIDs) are rare disorders caused by immune system defects that are commonly screened using multi-parameter flow cytometry (FCM). To counter the subjective and time-consuming manual data analysis of FCM data, we present PIDgeon, a fully automated computational pipeline based on artificial intelligence (AI) techniques. PIDgeon is designed to characterize PID immune profiles, suggest PID subtypes based on altered immune profiles, age, and immunoglobulin levels, and generate interpretable reports.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The PIDgeon pipeline, including FlowSOM and extreme gradient boosting models, was trained and tested on standardized FCM data generated according to EuroFlow procedures on 74 healthy controls and 399 patients (281 lymphoid-PID patients and 118 non-PID diseased controls) collected by the Ghent University Hospital. Subsequently, multi-centric validation was performed on internal (n = 211) and external (n = 338) independent data sets collected across 4 EuroFlow centers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Validation demonstrated high accuracy in cell count enumeration, achieving correlation scores above 0.90 for the major lymphocyte subsets. Interestingly, PIDgeon showed high sensitivity (93% to 100%) in predicting PID with severe T-cell defects, such as severe combined immunodeficiency and late-onset combined immunodeficiency, and low false-negative rates (1.5% to 5.4%) for distinguishing other lymphoid-PID vs non-PID diseased controls across data sets. Additionally, PIDgeon gives a first hint toward prediction of subtypes of primary antibody deficiencies, such as common variable immunodeficiency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In summary, PIDgeon is an accessible and explainable AI-pipeline aligned with current clinical needs, aiding laboratory immunologists in early PID diagnostics and increasing data analysis efficiency.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/clinchem\/hvaf190","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T12:57:02Z","timestamp":1765976222000},"page":"601-612","source":"Crossref","is-referenced-by-count":0,"title":["PIDgeon: An Explainable AI Model for Improved Flow Cytometry-Based Screening of Lymphoid Primary Immunodeficiencies"],"prefix":"10.1093","volume":"72","author":[{"given":"Annelies","family":"Emmaneel","sequence":"first","affiliation":[{"name":"Department of Mathematics, Computer Science and Statistics, Ghent University , Gent ,","place":["Belgium"]},{"name":"Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation Research , Gent ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0084-9245","authenticated-orcid":false,"given":"Jana","family":"Neirinck","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Sciences, Ghent University , Ghent ,","place":["Belgium"]},{"name":"Department of Laboratory Medicine, Ghent University Hospital , Ghent ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alba","family":"Torres-Valle","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC \u2013 University of Salamanca) , Salamanca ,","place":["Spain"]},{"name":"Cytometry Service, NUCLEUS , Department of Medicine, University of Salamanca, Salamanca ,","place":["Spain"]},{"name":"Institute of Biomedical Research of Salamanca (IBSAL) , Salamanca ,","place":["Spain"]},{"name":"Biomedical Research Networking Centre Consortium of Oncology (CIBERONC), Instituto de Salud Carlos III , Madrid ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7119-5330","authenticated-orcid":false,"given":"Sofie","family":"Van Gassen","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Computer Science and Statistics, Ghent University , Gent ,","place":["Belgium"]},{"name":"Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation Research , Gent ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Bonte","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Computer Science and Statistics, Ghent University , Gent ,","place":["Belgium"]},{"name":"Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation Research , Gent ,","place":["Belgium"]},{"name":"Department of Laboratory Medicine, Ghent University Hospital , Ghent ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malicorne","family":"Buysse","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Ghent University Hospital , Ghent ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques J M","family":"van Dongen","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC \u2013 University of Salamanca) , Salamanca ,","place":["Spain"]},{"name":"Cytometry Service, NUCLEUS , Department of Medicine, University of Salamanca, Salamanca ,","place":["Spain"]},{"name":"Institute of Biomedical Research of Salamanca (IBSAL) , Salamanca ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Orfao","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC \u2013 University of Salamanca) , Salamanca ,","place":["Spain"]},{"name":"Cytometry Service, NUCLEUS , Department of Medicine, University of Salamanca, Salamanca ,","place":["Spain"]},{"name":"Institute of Biomedical Research of Salamanca (IBSAL) , Salamanca ,","place":["Spain"]},{"name":"Biomedical Research Networking Centre Consortium of Oncology (CIBERONC), Instituto de Salud Carlos III , Madrid ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirjam","family":"van der Burg","sequence":"additional","affiliation":[{"name":"Laboratory for Pediatric Immunology, Department of Pediatrics, Leiden University Medical Center , Leiden ,","place":["the Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomas","family":"Kalina","sequence":"additional","affiliation":[{"name":"CLIP (Childhood Leukaemia Investigation Prague) , Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and Univ. Hospital Motol, Prague ,","place":["Czech Republic"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart N","family":"Lambrecht","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Immunology, VIB-UGhent Center for Inflammation Research, Ghent University , Ghent ,","place":["Belgium"]},{"name":"Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University , Ghent ,","place":["Belgium"]},{"name":"Department of Pulmonary Medicine, University Hospital Ghent , Ghent ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ciel","family":"De Vriendt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University , Ghent ,","place":["Belgium"]},{"name":"Department of Hematology, Ghent University Hospital , Ghent ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tessa","family":"Kerre","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University , Ghent ,","place":["Belgium"]},{"name":"Department of Hematology, Ghent University Hospital , Ghent ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filomeen","family":"Haerynck","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology and Immunology and PID Research Laboratory, Ghent University Hospital , Ghent ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"P\u00e9rez-Andr\u00e9s","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC \u2013 University of Salamanca) , Salamanca ,","place":["Spain"]},{"name":"Cytometry Service, NUCLEUS , Department of Medicine, University of Salamanca, Salamanca ,","place":["Spain"]},{"name":"Institute of Biomedical Research of Salamanca (IBSAL) , Salamanca ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mattias","family":"Hofmans","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Sciences, Ghent University , Ghent ,","place":["Belgium"]},{"name":"Department of Laboratory Medicine, Ghent University Hospital , Ghent ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolien","family":"Bonroy","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Sciences, Ghent University , Ghent ,","place":["Belgium"]},{"name":"Department of Laboratory Medicine, Ghent University Hospital , Ghent 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