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Systematic Identification of Single Amino Acid Variants in Glioma Stem-Cell-Derived Chromosome 19 Proteins

Lichti, Cheryl; Mostovenko, Ekaterina; Wadsworth, Paul; Lynch, Gillian; Pettitt, Montgomery; Sulman, Erik; Wang, Qiunghu; Lang, Frederick; Rezeli, Melinda LU and Marko-Varga, György LU , et al. (2015) In Journal of Proteome Research 14(2). p.778-786
Abstract
Novel proteoforms with single amino acid polymorphism represent proteins that often have altered biological functions but are less explored in the human proteome. We have developed an approach, searching high quality shotgun proteomic data against an extended protein database, to identify expressed mutant proteoforms in glioma stem cell (GSC) lines. The systematic search of MS/MS spectra has recognized 13 chromosome 19 proteins in GSCs with altered amino acid sequences using PEAKS 7.0 as the search engine. The results were further verified by manual spectral examination, validating 14 proteoforms. One of the novel findings, a mutant form of branched-chain aminoacyl transferase 2 (T186R), was verified at the transcript level and by SRM in... (More)
Novel proteoforms with single amino acid polymorphism represent proteins that often have altered biological functions but are less explored in the human proteome. We have developed an approach, searching high quality shotgun proteomic data against an extended protein database, to identify expressed mutant proteoforms in glioma stem cell (GSC) lines. The systematic search of MS/MS spectra has recognized 13 chromosome 19 proteins in GSCs with altered amino acid sequences using PEAKS 7.0 as the search engine. The results were further verified by manual spectral examination, validating 14 proteoforms. One of the novel findings, a mutant form of branched-chain aminoacyl transferase 2 (T186R), was verified at the transcript level and by SRM in several glioma stem cell lines. The structure of this proteoform examined by molecular modeling to estimate structural changes of mutation that could lead to functional modifications potentially linked to glioma. Based on our initial findings, we believe that our approach presented could contribute to construct a more complete map of the human functional proteome. (Less)
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keywords
Chromosome-centric Human Proteome Project, Chromosome 19, Mass spectrometry, Non-synonymous single nucleotide polymorphism, amino acid polymorphism, Glioma stem cells, Cancer proteomics, bioinformatics, SRM assay, BCAT2 T186R
in
Journal of Proteome Research
volume
14
issue
2
pages
778 - 786
publisher
The American Chemical Society
external identifiers
  • wos:000349276400018
  • scopus:84922662078
ISSN
1535-3893
DOI
10.1021/pr500810g
language
English
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yes
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7d38bd30-103a-4c83-822d-8ef1c07a7de6 (old id 4584310)
date added to LUP
2014-11-27 13:13:43
date last changed
2017-08-27 03:45:25
@article{7d38bd30-103a-4c83-822d-8ef1c07a7de6,
  abstract     = {Novel proteoforms with single amino acid polymorphism represent proteins that often have altered biological functions but are less explored in the human proteome. We have developed an approach, searching high quality shotgun proteomic data against an extended protein database, to identify expressed mutant proteoforms in glioma stem cell (GSC) lines. The systematic search of MS/MS spectra has recognized 13 chromosome 19 proteins in GSCs with altered amino acid sequences using PEAKS 7.0 as the search engine. The results were further verified by manual spectral examination, validating 14 proteoforms. One of the novel findings, a mutant form of branched-chain aminoacyl transferase 2 (T186R), was verified at the transcript level and by SRM in several glioma stem cell lines. The structure of this proteoform examined by molecular modeling to estimate structural changes of mutation that could lead to functional modifications potentially linked to glioma. Based on our initial findings, we believe that our approach presented could contribute to construct a more complete map of the human functional proteome.},
  author       = {Lichti, Cheryl and Mostovenko, Ekaterina and Wadsworth, Paul and Lynch, Gillian and Pettitt, Montgomery and Sulman, Erik and Wang, Qiunghu and Lang, Frederick and Rezeli, Melinda and Marko-Varga, György and Végvári, Ákos and Nilsson, Carol},
  issn         = {1535-3893},
  keyword      = {Chromosome-centric Human Proteome Project,Chromosome 19,Mass spectrometry,Non-synonymous single nucleotide polymorphism,amino acid polymorphism,Glioma stem cells,Cancer proteomics,bioinformatics,SRM assay,BCAT2 T186R},
  language     = {eng},
  number       = {2},
  pages        = {778--786},
  publisher    = {The American Chemical Society},
  series       = {Journal of Proteome Research},
  title        = {Systematic Identification of Single Amino Acid Variants in Glioma Stem-Cell-Derived Chromosome 19 Proteins},
  url          = {http://dx.doi.org/10.1021/pr500810g},
  volume       = {14},
  year         = {2015},
}