MODplus: Robust and Unrestrictive Identification of Post-Translational Modifications Using Mass Spectrometry

Analytical Chemistry
Seungjin NaEunok Paek

Abstract

Post-translational modifications regulate various cellular processes and are of great biological interest. Unrestrictive searches of mass spectrometry data enable the detection of any type of modification. Here we propose MODplus, which makes practical unrestrictive searches possible by allowing (1) hundreds of modifications, (2) multiple modifications per peptide, (3) the whole proteome database, and (4) any tolerant values in search parameters. The utility of MODplus was demonstrated in large human data sets of HEK293 cells and TMT-labeled phosphorylation enrichment. Notably, MODplus supports identifying different modification types at multiple sites and reports real chemical and biological modifications, as it has been very labor intensive to link unrestrictive search results to real modifications. We also confirmed the presence of Missing Precursor (MP) spectra that were not identifiable using targeted precursor masses. The MP spectra mostly resulted in identifications of wrong modifications and negatively affected the overall performance, often by as much as 10%. MODplus can rapidly recognize MP spectra and correct their identifications, resulting in increased identification rate up to 70% in the HEK293 data set as well as...Continue Reading

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Citations

Jul 9, 2020·Computational and Structural Biotechnology Journal·Seungjin Na, Eunok Paek
Apr 28, 2021·BMC Bioinformatics·Albane LysiakDominique Tessier
Apr 28, 2020·Journal of Proteome Research·Hui-Yin ChangAlexey I Nesvizhskii
Nov 13, 2019·Journal of Proteome Research·Seunghyuk ChoiEunok Paek

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