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Multiple urinary peptides display distinct sex-specific distribution
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  • Ioanna Mina,
  • Emmanouil Mavrogeorgis,
  • Justyna Siwy,
  • Riste Stojanov,
  • Harald Mischak,
  • Agnieszka Latosinska,
  • Vera Jankowski
Ioanna Mina
Mosaiques Diagnostics GmbH
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Emmanouil Mavrogeorgis
RWTH Aachen
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Justyna Siwy
Mosaiques-diagnostics
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Riste Stojanov
Cyril and Methodius University in Skopje
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Harald Mischak
Mosaiques diagnostics GmbH
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Agnieszka Latosinska
Mosaiques diagnostics GmbH
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Vera Jankowski
RWTH Aachen

Corresponding Author:vjankowski@ukaachen.de

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Abstract

Previous studies have established the association of sex with gene and protein expression. This study investigated the association of sex with the abundance of endogenous urinary peptides, using capillary electrophoresis-coupled to mass spectrometry datasets from 2008 healthy individuals and patients with type II diabetes, divided in one discovery and two validation cohorts. Statistical analysis using the Mann-Whitney test, adjusted for multiple testing, revealed 143 sex-associated peptides in the discovery cohort. Of these, 90 peptides were associated with sex in at least one of the validation cohorts and showed agreement in their regulation trends across all cohorts. The 90 sex-associated peptides were fragments of 29 parental proteins. Comparison with previously published transcriptomics data demonstrated that the genes encoding 16 of these parental proteins had sex-biased expression. The 143 sex-associated peptides were combined into a support vector machine-based classifier that could discriminate males from females in two independent sets of healthy individuals and patients with type II diabetes, with an AUC of 89% and 81%, respectively. Collectively, the urinary peptidome contains multiple sex-associated differences, which may enable a better understanding of sex-biased molecular mechanisms and the development of more accurate diagnostic, prognostic or predictive classifiers for each individual sex.
22 May 2023Submitted to PROTEOMICS
26 May 2023Submission Checks Completed
26 May 2023Assigned to Editor
26 May 2023Review(s) Completed, Editorial Evaluation Pending
26 May 2023Reviewer(s) Assigned
24 Jul 2023Editorial Decision: Revise Minor
08 Sep 2023Review(s) Completed, Editorial Evaluation Pending
08 Sep 20231st Revision Received
11 Sep 2023Editorial Decision: Accept