ISPTM

An iterative search algorithm for systematic identification of post-translational modifications from complex proteome mixtures

Xin Huang, Lin Huang, Hong Peng, Ashu Guru, Weihua Xue, Sang Yong Hong, Miao Liu, Seema Sharma, Kai Fu, Adam P. Caprez, David R Swanson, Zhixin Zhang, Shi Jian Ding

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Identifying protein post-translational modifications (PTMs) from tandem mass spectrometry data of complex proteome mixtures is a highly challenging task. Here we present a new strategy, named iterative search for identifying PTMs (ISPTM), for tackling this challenge. The ISPTM approach consists of a basic search with no variable modification, followed by iterative searches of many PTMs using a small number of them (usually two) in each search. The performance of the ISPTM approach was evaluated on mixtures of 70 synthetic peptides with known modifications, on an 18-protein standard mixture with unknown modifications and on real, complex biological samples of mouse nuclear matrix proteins with unknown modifications. ISPTM revealed that many chemical PTMs were introduced by urea and iodoacetamide during sample preparation and many biological PTMs, including dimethylation of arginine and lysine, were significantly activated by Adriamycin treatment in nuclear matrix associated proteins. ISPTM increased the MS/MS spectral identification rate substantially, displayed significantly better sensitivity for systematic PTM identification compared with that of the conventional all-in-one search approach, and offered PTM identification results that were complementary to InsPecT and MODa, both of which are established PTM identification algorithms. In summary, ISPTM is a new and powerful tool for unbiased identification of many different PTMs with high confidence from complex proteome mixtures.

Original languageEnglish (US)
Pages (from-to)3831-3842
Number of pages12
JournalJournal of Proteome Research
Volume12
Issue number9
DOIs
StatePublished - Sep 6 2013

Fingerprint

Pulse time modulation
Proteome
Post Translational Protein Processing
Complex Mixtures
Nuclear Matrix-Associated Proteins
Iodoacetamide
Doxorubicin
Lysine
Mass spectrometry
Arginine
Urea
Proteins
Peptides
Tandem Mass Spectrometry

Keywords

  • DNA damage
  • ISPTM
  • OMSSA
  • database search
  • nuclear matrix
  • post-translational modifications

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

ISPTM : An iterative search algorithm for systematic identification of post-translational modifications from complex proteome mixtures. / Huang, Xin; Huang, Lin; Peng, Hong; Guru, Ashu; Xue, Weihua; Hong, Sang Yong; Liu, Miao; Sharma, Seema; Fu, Kai; Caprez, Adam P.; Swanson, David R; Zhang, Zhixin; Ding, Shi Jian.

In: Journal of Proteome Research, Vol. 12, No. 9, 06.09.2013, p. 3831-3842.

Research output: Contribution to journalArticle

Huang, Xin ; Huang, Lin ; Peng, Hong ; Guru, Ashu ; Xue, Weihua ; Hong, Sang Yong ; Liu, Miao ; Sharma, Seema ; Fu, Kai ; Caprez, Adam P. ; Swanson, David R ; Zhang, Zhixin ; Ding, Shi Jian. / ISPTM : An iterative search algorithm for systematic identification of post-translational modifications from complex proteome mixtures. In: Journal of Proteome Research. 2013 ; Vol. 12, No. 9. pp. 3831-3842.
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