title: Identification of ultramodified proteins using top-down tandem mass spectra.
abstract: Post-translational modifications (PTMs) play an important role in various biological processes through changing protein structure and function. Some ultramodified proteins (like histones) have multiple PTMs forming PTM patterns that define the functionality of a protein. While bottom-up mass spectrometry (MS) has been successful in identifying individual PTMs within short peptides, it is unable to identify PTM patterns spreading along entire proteins in a coordinated fashion. In contrast, top-down MS analyzes intact proteins and reveals PTM patterns along the entire proteins. However, while recent advances in instrumentation have made top-down MS accessible to many laboratories, most computational tools for top-down MS focus on proteins with few PTMs and are unable to identify complex PTM patterns. We propose a new algorithm, MS-Align-E, that identifies both expected and unexpected PTMs in ultramodified proteins. We demonstrate that MS-Align-E identifies many proteoforms of histone H4 and benchmark it against the currently accepted software tools.
authors.affiliation: Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis , Indianapolis, IN 46202, United States.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liu
authors.forename: Shawna
authors.initials: S
authors.lastname: Hengel
authors.forename: Si
authors.initials: S
authors.lastname: Wu
authors.forename: Nikola
authors.initials: N
authors.lastname: Tolić
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Pasa-Tolić
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Pevzner
mesh_terms: D000107:Acetylation; D000465:Algorithms; D000595:Amino Acid Sequence; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods*; D016415:Sequence Alignment; D012984:Software; D053719:Tandem Mass Spectrometry
chemical_list: D006657:Histones