LC–MS/MS-Based Absolute Quantitation of Hemoglobin Subunits from Dried Blood Spots Reveals Novel Biomarkers for α-Thalassemia Silent Carriers
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Le résumé fourni par la source
Identification of α-thalassemia silent carriers is challenging with conventional phenotype-based screening methods. A liquid chromatography tandem mass spectrometry (LC-MS/MS)-based approach may offer novel biomarkers to address this conundrum. In this study, we collected dried blood spot samples from individuals with three α-thalassemia subtypes for biomarker discovery and validation. We observed differential expression patterns of hemoglobin subunits among various α-thalassemia subtypes and normal controls through proteomic profiling of 51 samples in the discovery phase. Then, we developed and optimized a multiple reaction monitoring (MRM) assay to measure all detectable hemoglobin subunits. The validation phase was conducted in a cohort of 462 samples. Among the measured hemoglobin subunits, subunit μ was significantly upregulated in all the α-thalassemia groups with distinct fold changes. The hemoglobin subunit μ exhibits great potential as a novel biomarker for α-thalassemia, especially for silent α-thalassemia. We constructed predictive models based on the concentrations of hemoglobin subunits and their ratios to classify the various subtypes of α-thalassemia. In the binary classification problems of silent α-thalassemia vs normal, non-deletional α-thalassemia vs normal, and deletional α-thalassemia vs normal, the best performance of the models achieved average ROCAUCs of 0.9505, 0.9430, and 0.9976 in the cross-validation, respectively. In the multiclass model, the best performance achieved an average ROCAUC of 0.9290 in cross-validation. The performance of our MRM assay and models demonstrated that the hemoglobin subunit μ would play a vital role in screening silent α-thalassemia in clinical practice.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- LC–MS/MS-Based Absolute Quantitation of Hemoglobin Subunits from Dried Blood Spots Reveals Novel Biomarkers for α-Thalassemia Silent Carriers
- Date Crossref
- 07/06/2023
- Éditeur
- American Chemical Society (ACS)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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BGI Group (China) pays non établi dans la noticeEntreprise
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BGI Genomics pays non établi dans la noticeEntreprise
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Dongguan People’s Hospital pays non établi dans la noticeÉtablissement de santé
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Southern Medical University Dongguan Maternal and Child Health Care Hospital pays non établi dans la noticeUniversité ou école supérieure
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Shenzhen Technology University pays non établi dans la noticeUniversité ou école supérieure
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Nanfang Hospital pays non établi dans la noticeÉtablissement de santé
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Clinical Laboratory of BGI Health pays non établi dans la noticeStructure de recherche
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School of Basic Medical Sciences Department of Medical Genetics pays non établi dans la noticeUniversité ou école supérieure
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Huizhou First Maternal and Child Health Care Hospital Department of Medical Genetics and Prenatal Diagnosis pays non établi dans la noticeÉtablissement de santé
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College of Pharmacy pays non établi dans la noticeUniversité ou école supérieure
BGI Group (China), BGI Genomics et Dongguan People’s Hospital, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.