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A mass spectrometry–friendly database for cSNP identification

Nature Methods volume 4, pages 465–466 (2007)Cite this article

To the editor:

Mass spectrometry (MS)-based proteomics is performed in different experimental formats, which today almost always involve matching fragmented peptides to a database1. Different protein sequence databases strike different balances between inclusion of as many protein isoforms as possible and minimal redundancy. The European Bioinformatics Institute (EBI) International Protein Sequence (IPI) database2 contains about 68,000 human protein entries and is widely used in proteomics. IPI stores the longest sequence available for each entry, which means that the N-terminal peptide of secreted proteins, for example, appears to be 'half-tryptic' and is not reported when requiring complete sequence specificity of the protease used to degrade proteins to peptides3. IPI also does not contain information about conflicting sequence entries contained in the Swiss-Prot database. Furthermore, the genomes of individuals of a species are not identical but contain single nucleotide polymorphisms (SNPs) roughly every 1,000 base pairs at an appreciable frequency in the population4. When these SNPs occur in coding regions (coding SNPs or cSNPs), they change protein primary structure and could in principle be detected by proteomics approaches. In practice, however, this information is not carried through to protein sequence databases.

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Figure 1: Identification of cSNP peptides via a modified database.
Figure 2: Construction of the modified IPI database.

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Acknowledgements

We thank P. Kersey of the EMBL-European Bioinformatics Institute for distributing MSIPI from EBI. The Center for Experimental BioInformatics is supported by the Danish National Research Foundation and the Danish Platform for Integrative Biology.

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Authors and Affiliations

  1. Center for Experimental BioInformatics, University of Southern Denmark, Campusvej 55, Odense M, DK-5230, Denmark

    Søren Schandorff, Jakob Bunkenborg, Blagoy Blagoev, Jens S Andersen & Matthias Mann

  2. Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried, D-82152, Germany

    Jesper V Olsen, Yong Zhang & Matthias Mann

Authors
  1. Søren Schandorff
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  2. Jesper V Olsen
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  3. Jakob Bunkenborg
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Supplementary information

Supplementary Table 1

List of identified peptides. (PDF 44 kb)

Supplementary Data

Annotated fragmentation spectra for all identified cSNPs. (PDF 1628 kb)

Supplementary Methods (PDF 90 kb)

Supplementary Discussion (PDF 17 kb)

Supplementary Software

MSIPI software scripts for linux in tar format and gzipped. (ZIP 23 kb)

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Schandorff, S., Olsen, J., Bunkenborg, J. et al. A mass spectrometry–friendly database for cSNP identification. Nat Methods 4, 465–466 (2007). https://doi.org/10.1038/nmeth0607-465

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