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

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.