Detection of Unknown Amino Acid Substitutions Using Error-Tolerant Database Search

  • Sven H. Giese
  • Franziska Zickmann
  • Bernhard Y. Renard
Part of the Methods in Molecular Biology book series (MIMB, volume 1362)

Abstract

Recent studies have demonstrated that mass spectrometry-based variant detection is feasible. Typically, either genomic variant databases or transcript data are used to construct customized target databases for the identification of single-amino acid variants in mass spectrometry data. However, both approaches require additional data to perform the identification of SAAVs. Here, we discuss the application of an error-tolerant peptide search engine such as BICEPS for identifying variants exclusively based on standard Uniprot databases. Thereby, unnecessary and redundant extensions of the search space are avoided. The workflow provides an unbiased view on the data; the search space is not limited to known variants and simultaneously does not require additional data. In a subsequent step a second identification search is performed to verify the initially identified variant peptides and aggregate information on the protein level.

Key words

Mass spectrometry Variant peptide identification Error-tolerant peptide identification Single-amino acid variations Single-nucleotide variants Proteomics 

Notes

Acknowledgment

The authors gratefully acknowledge financial support by Deutsche Forschungsgemeinschaft (DFG), grant number (RE3474/2-1 to BYR).

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Sven H. Giese
    • 1
    • 2
    • 3
  • Franziska Zickmann
    • 1
  • Bernhard Y. Renard
    • 1
  1. 1.Research Group Bioinformatics (NG4)Robert Koch-InstituteBerlinGermany
  2. 2.Department of Bioanalytics, Institute of BiotechnologyTechnische Universität BerlinBerlinGermany
  3. 3.Wellcome Trust Centre for Cell Biology, School of Biological SciencesUniversity of EdinburghEdinburghUK

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