PTMoreR-enabled cross-species PTM mapping and comparative phosphoproteomics across mammals

Cell Rep Methods. 2024 Sep 16;4(9):100859. doi: 10.1016/j.crmeth.2024.100859. Epub 2024 Sep 9.

Abstract

To support PTM proteomic analysis and annotation in different species, we developed PTMoreR, a user-friendly tool that considers the surrounding amino acid sequences of PTM sites during BLAST, enabling a motif-centric analysis across species. By controlling sequence window similarity, PTMoreR can map phosphoproteomic results between any two species, perform site-level functional enrichment analysis, and generate kinase-substrate networks. We demonstrate that the majority of real P-sites in mice can be inferred from experimentally derived human P-sites with PTMoreR mapping. Furthermore, the compositions of 129 mammalian phosphoproteomes can also be predicted using PTMoreR. The method also identifies cross-species phosphorylation events that occur on proteins with an increased tendency to respond to the environmental factors. Moreover, the classic kinase motifs can be extracted across mammalian species, offering an evolutionary angle for refining current motifs. PTMoreR supports PTM proteomics in non-human species and facilitates quantitative phosphoproteomic analysis.

Keywords: CP: biotechnology; CP: systems biology; bioinformatics; cross-species mapping; evolution biology; kinase-substrate annotation; mass spectrometry-based proteomics; motif-centric; phosphoproteomics; post-translational modification; site-specific enrichment analysis; window similarity.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Humans
  • Mammals* / metabolism
  • Mice
  • Phosphoproteins* / chemistry
  • Phosphoproteins* / metabolism
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Proteome / metabolism
  • Proteomics* / methods
  • Software
  • Species Specificity

Substances

  • Phosphoproteins
  • Proteome