Machine Learning-Based Prediction of Hemoglobinopathies Using Complete Blood Count Data
Clinical Chemistry, vol. 70, pp. 1064–1075
Abstract
BACKGROUND: 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. METHODS: 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). RESULTS: 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 β-thalassemia, 0.98 for α0-thalassemia, 0.95 for homozygous α+-thalassemia, 0.78 for heterozygous α+-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. CONCLUSIONS: 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.
Authors 17
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Radboud University Nijmegen · Radboud University Medical Center · Jeroen Bosch Ziekenhuis
Affiliation as printed
Diagnostic Image Analysis Group, Radboudumc , Nijmegen , the Netherlands
Laboratory of Clinical Chemistry and Hematology, Jeroen Bosch Hospital’s , Hertogenbosch , the Netherlands
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Radboud University Nijmegen · Radboud University Medical Center · Jeroen Bosch Ziekenhuis
Affiliation as printed
Department of Radiology, Jeroen Bosch Hospital’s , Hertogenbosch , the Netherlands
Diagnostic Image Analysis Group, Radboudumc , Nijmegen , the Netherlands
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Affiliation as printed
Laboratory of Clinical Chemistry and Laboratory Medicine, Amphia Hospital , Breda , the Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Clinical Genetics, Laboratory for Genome Diagnostics, Leiden University Medical Center , Leiden , the Netherlands
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Affiliation as printed
Laboratory of Hematology, Hospital Universitario Galdakao Usansolo , Galdakao , Spain
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Affiliation as printed
Laboratory of Clinical Chemistry, Maasstad Hospital , Rotterdam , the Netherlands
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Affiliation as printed
Laboratory of Clinical Chemistry and Laboratory Medicine, Isala Hospital , Zwolle , the Netherlands
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Affiliation as printed
Laboratory of Clinical Chemistry and Hematology, Medisch Spectrum Twente/Medlon BV , Enschede , the Netherlands
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Affiliation as printed
Laboratory of Clinical Chemistry and Hematology, Medisch Spectrum Twente/Medlon BV , Enschede , the Netherlands
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Maasstad Ziekenhuis · Canisius-Wilhelmina Ziekenhuis
Affiliation as printed
Laboratory of Clinical Chemistry and Laboratory Medicine, Canisius Wilhelmina Hospital , Nijmegen , the Netherlands
Laboratory of Clinical Chemistry, Maasstad Hospital , Rotterdam , the Netherlands
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Affiliation as printed
Laboratory of Clinical Chemistry and Laboratory Medicine, Máxima Medical Center , Eindhoven , the Netherlands
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Affiliation as printed
Laboratory of Clinical Chemistry and Laboratory Medicine, Meander Medical Center , Amersfoort , the Netherlands
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Affiliation as printed
Department of Clinical Chemistry and Haematology, Zuyderland Medical Center , Sittard/Heerlen , the Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Clinical Genetics, Laboratory for Genome Diagnostics, Leiden University Medical Center , Leiden , the Netherlands
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Radboud University Nijmegen · Radboud University Medical Center
Affiliation as printed
Diagnostic Image Analysis Group, Radboudumc , Nijmegen , the Netherlands
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Jeroen Bosch Ziekenhuis · University of Twente
Affiliation as printed
Department of Health Technology and Services Research, Technical Medical Centre, University of Twente , Enschede , the Netherlands
Laboratory of Clinical Chemistry and Hematology, Jeroen Bosch Hospital’s , Hertogenbosch , the Netherlands
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Steef Kurstjens corresponding
Affiliation as printed
Laboratory of Clinical Chemistry and Hematology, Jeroen Bosch Hospital’s , Hertogenbosch , the Netherlands
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