Comprehensive Peptide Mapping Is Crucial for Proteogenomics and Proteomics

Proteogenomics enables the confirmation and refinement of gene models, the detection of new ones, and the proposition of alternative transcripts using support at the protein level. Such evidence is usually generated using mass spectrometry and subsequent result mapping to various sequence databases. This workflow entails several problems: (1) To speed up the analysis, only a small set of expected proteins is searched; (2) database search tools generally do not provide mapping to the genome; and (3) upon new releases of the sequence databases, expensive rerunning of all results would need to be performed. Therefore, fast and accurate peptide mapping is needed as part of proteogenomic pipelines. Unfortunately, some available tools have technical shortcomings. Thus, a set of test cases was developed to allow tool developers to test their implementations comprehensively. The need for comprehensive testing is exemplified by PGx and PGM, two published tools that could only solve a subset of test cases. Lelantos passed all test cases. A set of comprehensive test cases has been developed to overcome these issues. Many unpublished peptide mapping tools are part of proteogenomic workflows, and such tools would also benefit from comprehensive testing. Finally, peptide mapping may also be crucial for proteomics because sequence databases change over time. In response, peptide remapping should be performed to ensure that peptides identifying a protein are proteotypic in a larger sequence context.