Multivariate analyses for biomarkers hunting and validation through on-tissue bottom-up or in-source decay in MALDI-MSI: application to prostate cancer |
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Authors: | David Bonnel Rémi Longuespee Julien Franck Morad Roudbaraki Pierre Gosset Robert Day Michel Salzet Isabelle Fournier |
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Institution: | 1.MALDI Imaging team, Laboratoire de Spectrométrie de Masse Biologique Fondamentale et Appliquée (FABMS), EA 4550,Université Nord de France,Villeneuve d’Ascq,France;2.Institut de pharmacologie de Sherbrooke, Faculté de médecine et des Sciences de la santé,Université de Sherbrooke,Sherbrooke,Canada;3.INSERM, U-1003, Equipe labellisée par la Ligue Nationale contre le cancer,Université Nord de France,Villeneuve d’Ascq,France;4.Faculté Libre de Médecine, Laboratoire d’Anatomie et de Cytologie Pathologique du groupement hospitalier de l’Institut Catholique de Lille,Lille,France |
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Abstract: | The large amount of data generated using matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI)
poses a challenge for data analysis. In fact, generally about 1.108–1.109 values (m/z, I) are stored after a single MALDI-MSI experiment. This imposes processing techniques using dedicated informatics tools
to be used since manual data interpretation is excluded. This work proposes and summarizes an approach that utilizes a multivariable
analysis of MSI data. The multivariate analysis, such as principal component analysis–symbolic discriminant analysis, can
remove and highlight specific m/z from the spectra in a specific region of interest. This approach facilitates data processing and provides better reproducibility,
and thus, broadband acquisition for MALDI-MSI should be considered an effective tool to highlight biomarkers of interest.
Additionally, we demonstrate the importance of the hierarchical classification of biomarkers by analyzing studies of clusters
obtained either from digested or undigested tissues and using bottom-up and in-source decay strategies for in-tissue protein
identification. This provides the possibility for the rapid identification of specific markers from different histological
samples and their direct localization in tissues. We present an example from a prostate cancer study using formalin-fixed
paraffin-embedded tissue. |
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