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Peptide clustering enhances large-scale analyses and reveals proteolytic signatures in mass spectrometry data

Erik Hartman (), Fredrik Forsberg, Sven Kjellström, Jitka Petrlova, Congyu Luo, Aaron Scott, Manoj Puthia, Johan Malmström and Artur Schmidtchen
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Erik Hartman: Lund University
Fredrik Forsberg: Lund University
Sven Kjellström: Lund University
Jitka Petrlova: Lund University
Congyu Luo: Lund University
Aaron Scott: Lund University
Manoj Puthia: Lund University
Johan Malmström: Lund University
Artur Schmidtchen: Lund University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Recent advances in mass spectrometry-based peptidomics have catalyzed the identification and quantification of thousands of endogenous peptides across diverse biological systems. However, the vast peptidomic landscape generated by proteolytic processing poses several challenges for downstream analyses and limits the comparability of clinical samples. Here, we present an algorithm that aggregates peptides into peptide clusters, reducing the dimensionality of peptidomics data, improving the definition of protease cut sites, enhancing inter-sample comparability, and enabling the implementation of large-scale data analysis methods akin to those employed in other omics fields. We showcase the algorithm by performing large-scale quantitative analysis of wound fluid peptidomes of highly defined porcine wound infections and human clinical non-healing wounds. This revealed signature phenotype-specific peptide regions and proteolytic activity at the earliest stages of bacterial colonization. We validated the method on the urinary peptidome of type 1 diabetics which revealed potential subgroups and improved classification accuracy.

Date: 2024
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DOI: 10.1038/s41467-024-51589-y

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