Identification of post-translational modifications by blind search of mass spectra

Dekel Tsur; Stephen Tanner; Ebrahim Zandi; Vineet Bafna; Pavel A. Pevzner

doi:10.1038/nbt1168

Identification of post-translational modifications by blind search of mass spectra

Dekel Tsur, Stephen Tanner, Ebrahim Zandi, Vineet Bafna, Pavel A. Pevzner

Research output: Contribution to journal › Article › peer-review

228 Scopus citations

Abstract

Most tandem mass spectrometry (MS/MS) database search algorithms perform a restrictive search that takes into account only a few types of post-translational modifications (PTMs) and ignores all others. We describe an unrestrictive PTM search algorithm, MS-Alignment, that searches for all types of PTMs at once in a blind mode, that is, without knowing which PTMs exist in nature. Blind PTM identification makes it possible to study the extent and frequency of different types of PTMs, still an open problem in proteomics. Application of this approach to lens proteins resulted in the largest set of PTMs reported in human crystallins so far. Our analysis of various MS/MS data sets implies that the biological phenomenon of modification is much more widespread than previously thought. We also argue that MS-Alignment reveals some uncharacterized modifications that warrant further experimental validation.

Original language	English
Pages (from-to)	1562-1567
Number of pages	6
Journal	Nature Biotechnology
Volume	23
Issue number	12
DOIs	https://doi.org/10.1038/nbt1168
State	Published - 1 Dec 2005
Externally published	Yes

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

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10.1038/nbt1168

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title = "Identification of post-translational modifications by blind search of mass spectra",

abstract = "Most tandem mass spectrometry (MS/MS) database search algorithms perform a restrictive search that takes into account only a few types of post-translational modifications (PTMs) and ignores all others. We describe an unrestrictive PTM search algorithm, MS-Alignment, that searches for all types of PTMs at once in a blind mode, that is, without knowing which PTMs exist in nature. Blind PTM identification makes it possible to study the extent and frequency of different types of PTMs, still an open problem in proteomics. Application of this approach to lens proteins resulted in the largest set of PTMs reported in human crystallins so far. Our analysis of various MS/MS data sets implies that the biological phenomenon of modification is much more widespread than previously thought. We also argue that MS-Alignment reveals some uncharacterized modifications that warrant further experimental validation.",

author = "Dekel Tsur and Stephen Tanner and Ebrahim Zandi and Vineet Bafna and Pevzner, {Pavel A.}",

note = "Funding Information: This project was supported by National Institutes of Health grant NIGMS 1-R01-RR16522. We are grateful to Brian Searle and Larry David for making their lens data set available and to Larry David, Katalin Medzihradszky and Philip Wilmarth for many useful discussions. Production of the lens data set was supported by National Eye Institute grant EY007755. This research was supported in part by the UCSD FWGrid Project, NSF Research Infrastructure Grant Number EIA-0303622. Production of the IKKb data set was supported by NIH grant R01GM65325 and by the Pew Scholars Program.",

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AU - Tanner, Stephen

AU - Zandi, Ebrahim

AU - Bafna, Vineet

AU - Pevzner, Pavel A.

N1 - Funding Information: This project was supported by National Institutes of Health grant NIGMS 1-R01-RR16522. We are grateful to Brian Searle and Larry David for making their lens data set available and to Larry David, Katalin Medzihradszky and Philip Wilmarth for many useful discussions. Production of the lens data set was supported by National Eye Institute grant EY007755. This research was supported in part by the UCSD FWGrid Project, NSF Research Infrastructure Grant Number EIA-0303622. Production of the IKKb data set was supported by NIH grant R01GM65325 and by the Pew Scholars Program.

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N2 - Most tandem mass spectrometry (MS/MS) database search algorithms perform a restrictive search that takes into account only a few types of post-translational modifications (PTMs) and ignores all others. We describe an unrestrictive PTM search algorithm, MS-Alignment, that searches for all types of PTMs at once in a blind mode, that is, without knowing which PTMs exist in nature. Blind PTM identification makes it possible to study the extent and frequency of different types of PTMs, still an open problem in proteomics. Application of this approach to lens proteins resulted in the largest set of PTMs reported in human crystallins so far. Our analysis of various MS/MS data sets implies that the biological phenomenon of modification is much more widespread than previously thought. We also argue that MS-Alignment reveals some uncharacterized modifications that warrant further experimental validation.

AB - Most tandem mass spectrometry (MS/MS) database search algorithms perform a restrictive search that takes into account only a few types of post-translational modifications (PTMs) and ignores all others. We describe an unrestrictive PTM search algorithm, MS-Alignment, that searches for all types of PTMs at once in a blind mode, that is, without knowing which PTMs exist in nature. Blind PTM identification makes it possible to study the extent and frequency of different types of PTMs, still an open problem in proteomics. Application of this approach to lens proteins resulted in the largest set of PTMs reported in human crystallins so far. Our analysis of various MS/MS data sets implies that the biological phenomenon of modification is much more widespread than previously thought. We also argue that MS-Alignment reveals some uncharacterized modifications that warrant further experimental validation.

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Identification of post-translational modifications by blind search of mass spectra

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