{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:16:48Z","timestamp":1791375408890,"version":"4.3.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,6,22]],"date-time":"2024-06-22T00:00:00Z","timestamp":1719014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Hemoglobinopathies, the most common inherited blood disorder, are frequently underdiagnosed. Early identification of carriers is important for genetic counseling of couples at risk. The aim of this study was to develop and validate a novel machine learning model on a multicenter data set, covering a wide spectrum of hemoglobinopathies based on routine complete blood count (CBC) testing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Hemoglobinopathy test results from 10 322 adults were extracted retrospectively from 8 Dutch laboratories. eXtreme Gradient Boosting (XGB) and logistic regression models were developed to differentiate negative from positive hemoglobinopathy cases, using 7 routine CBC parameters. External validation was conducted on a data set from an independent Dutch laboratory, with an additional external validation on a Spanish data set (n = 2629) specifically for differentiating thalassemia from iron deficiency anemia (IDA).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The XGB and logistic regression models achieved an area under the receiver operating characteristic (AUROC) of 0.88 and 0.84, respectively, in distinguishing negative from positive hemoglobinopathy cases in the independent external validation set. Subclass analysis showed that the XGB model reached an AUROC of 0.97 for \u03b2-thalassemia, 0.98 for \u03b10-thalassemia, 0.95 for homozygous \u03b1+-thalassemia, 0.78 for heterozygous \u03b1+-thalassemia, and 0.94 for the structural hemoglobin variants Hemoglobin C, Hemoglobin D, Hemoglobin E. Both models attained AUROCs of 0.95 in differentiating IDA from thalassemia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Both the XGB and logistic regression model demonstrate high accuracy in predicting a broad range of hemoglobinopathies and are effective in differentiating hemoglobinopathies from IDA. Integration of these models into the laboratory information system facilitates automated hemoglobinopathy detection using routine CBC parameters.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/clinchem\/hvae081","type":"journal-article","created":{"date-parts":[[2024,6,22]],"date-time":"2024-06-22T02:31:34Z","timestamp":1719023494000},"page":"1064-1075","source":"Crossref","is-referenced-by-count":34,"title":["Machine Learning-Based Prediction of Hemoglobinopathies Using Complete Blood Count Data"],"prefix":"10.1093","volume":"70","author":[{"given":"Anoeska","family":"Schipper","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Chemistry and Hematology, Jeroen Bosch Hospital\u2019s , Hertogenbosch , the Netherlands"},{"name":"Diagnostic Image Analysis Group, Radboudumc , Nijmegen , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Rutten","sequence":"additional","affiliation":[{"name":"Diagnostic Image Analysis Group, Radboudumc , Nijmegen , the Netherlands"},{"name":"Department of Radiology, Jeroen Bosch Hospital\u2019s , Hertogenbosch , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan","family":"van Gammeren","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Chemistry and Laboratory Medicine, Amphia Hospital , Breda , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis L","family":"Harteveld","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Laboratory for Genome Diagnostics, Leiden University Medical Center , Leiden , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elo\u00edsa","family":"Urrechaga","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology, Hospital Universitario Galdakao Usansolo , Galdakao , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floor","family":"Weerkamp","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Chemistry, Maasstad Hospital , Rotterdam , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gijs","family":"den Besten","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Chemistry and Laboratory Medicine, Isala Hospital , Zwolle , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Krabbe","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Chemistry and Hematology, Medisch Spectrum Twente\/Medlon BV , Enschede , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennichjen","family":"Slomp","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Chemistry and Hematology, Medisch Spectrum Twente\/Medlon BV , Enschede , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lise","family":"Schoonen","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Chemistry, Maasstad Hospital , Rotterdam , the Netherlands"},{"name":"Laboratory of Clinical Chemistry and Laboratory Medicine, Canisius Wilhelmina Hospital , Nijmegen , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Broeren","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Chemistry and Laboratory Medicine, M\u00e1xima Medical Center , Eindhoven , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merel","family":"van Wijnen","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Chemistry and Laboratory Medicine, Meander Medical Center , Amersfoort , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirelle J A J","family":"Huijskens","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Haematology, Zuyderland Medical Center , Sittard\/Heerlen , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Koopmann","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Laboratory for Genome Diagnostics, Leiden University Medical Center , Leiden , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bram","family":"van Ginneken","sequence":"additional","affiliation":[{"name":"Diagnostic Image Analysis Group, Radboudumc , Nijmegen , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1279-5448","authenticated-orcid":false,"given":"Ron","family":"Kusters","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Chemistry and Hematology, Jeroen Bosch Hospital\u2019s , Hertogenbosch , the 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