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Identification of hemoglobin variants by top-down mass spectrometry using selected diagnostic product ions

Coelho Graça, Didia ; Hartmer, Ralf ; Jabs, Wolfgang ; Beris, Photis ; Clerici, Lorella ; Stoermer, Carsten ; Samii, Kaveh ; Hochstrasser, Denis ; Tsybin, Yury ; Scherl, Alexander ; Lescuyer, Pierre

In: Analytical and Bioanalytical Chemistry, 2015, vol. 407, no. 10, p. 2837-2845

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    Titre
    • Identification of hemoglobin variants by top-down mass spectrometry using selected diagnostic product ions
    Auteur
    • Coelho Graça, Didia. Department of Human Protein Sciences, Faculty of Medicine, Geneva University, Rue Michel Servet 1, 1211, Geneva, Switzerland
    • Hartmer, Ralf. Bruker Daltonics, Fahrenheitstraße 4, 28359, Bremen, Germany
    • Jabs, Wolfgang. Bruker Daltonics, Fahrenheitstraße 4, 28359, Bremen, Germany
    • Beris, Photis. Hematology Service, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205, Geneva, Switzerland
    • Clerici, Lorella. Department of Genetic and Laboratory Medicine, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205, Geneva, Switzerland
    • Stoermer, Carsten. Bruker Daltonics, Fahrenheitstraße 4, 28359, Bremen, Germany
    • Samii, Kaveh. Hematology Service, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205, Geneva, Switzerland
    • Hochstrasser, Denis. Department of Human Protein Sciences, Faculty of Medicine, Geneva University, Rue Michel Servet 1, 1211, Geneva, Switzerland
    • Tsybin, Yury. Biomolecular Mass Spectrometry Laboratory, Ecole Polytechnique Fédérale de Lausanne, 1015, Lausanne, Switzerland
    • Scherl, Alexander. Department of Human Protein Sciences, Faculty of Medicine, Geneva University, Rue Michel Servet 1, 1211, Geneva, Switzerland
    • Lescuyer, Pierre. Department of Human Protein Sciences, Faculty of Medicine, Geneva University, Rue Michel Servet 1, 1211, Geneva, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Analytical and Bioanalytical Chemistry, 2015, vol. 407, no. 10, p. 2837-2845. Springer Berlin Heidelberg
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:332175
    Summary
    Hemoglobin disorder diagnosis is a complex procedure combining several analytical steps. Due to the lack of specificity of the currently used protein analysis methods, the identification of uncommon hemoglobin variants (proteoforms) can become a hard task to accomplish. The aim of this work was to develop a mass spectrometry-based approach to quickly identify mutated protein sequences within globin chain variants. To reach this goal, a top-down electron transfer dissociation mass spectrometry method was developed for hemoglobin β chain analysis. A diagnostic product ion list was established with a color code strategy allowing to quickly and specifically localize a mutation in the hemoglobin β chain sequence. The method was applied to the analysis of rare hemoglobin β chain variants and an Aγ-β fusion protein. The results showed that the developed data analysis process allows fast and reliable interpretation of top-down electron transfer dissociation mass spectra by nonexpert users in the clinical area.