title: Discovery of protein acetylation patterns by deconvolution of peptide isomer mass spectra.
abstract: Protein post-translational modifications (PTMs) play important roles in the control of various biological processes including protein-protein interactions, epigenetics and cell cycle regulation. Mass spectrometry-based proteomics approaches enable comprehensive identification and quantitation of numerous types of PTMs. However, the analysis of PTMs is complicated by the presence of indistinguishable co-eluting isomeric peptides that result in composite spectra with overlapping features that prevent the identification of individual components. In this study, we present Iso-PeptidAce, a novel software tool that enables deconvolution of composite MS/MS spectra of isomeric peptides based on features associated with their characteristic fragment ion patterns. We benchmark Iso-PeptidAce using dilution series prepared from mixtures of known amounts of synthetic acetylated isomers. We also demonstrate its applicability to different biological problems such as the identification of site-specific acetylation patterns in histones bound to chromatin assembly factor-1 and profiling of histone acetylation in cells treated with different classes of HDAC inhibitors.
authors.affiliation: Department of Chemistry, Université de Montréal, PO Box 6128, Station centre-ville, Montréal, Québec, Canada H3C 3J7.|Institute for Research in Immunology and Cancer, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: Nebiyu
authors.initials: N
authors.lastname: Abshiru
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: Olivier
authors.initials: O
authors.lastname: Caron-Lizotte
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, Québec, Canada H3C 3J7.|Molecular Biology Programme, Université de Montréal, PO Box 6128, Station centre-ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: Roshan Elizabeth
authors.initials: RE
authors.lastname: Rajan
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: Adil
authors.initials: A
authors.lastname: Jamai
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: Christelle
authors.initials: C
authors.lastname: Pomies
authors.affiliation: Department of Chemistry, Université de Montréal, PO Box 6128, Station centre-ville, Montréal, Québec, Canada H3C 3J7.|Molecular Biology Programme, Université de Montréal, PO Box 6128, Station centre-ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: Alain
authors.initials: A
authors.lastname: Verreault
authors.affiliation: Department of Chemistry, Université de Montréal, PO Box 6128, Station centre-ville, Montréal, Québec, Canada H3C 3J7.|Institute for Research in Immunology and Cancer, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: Pierre
authors.initials: P
authors.lastname: Thibault
mesh_terms: D000107:Acetylation; D051548:Histone Acetyltransferases / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D013058:Mass Spectrometry; D011499:Protein Processing, Post-Translational; D012260:Ribonucleases; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012984:Software
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D051548:Histone Acetyltransferases; D012260:Ribonucleases; C079009:POP2 protein, S cerevisiae