期刊
PROTEOMICS
卷 22, 期 10, 页码 -出版社
WILEY
DOI: 10.1002/pmic.202100226
关键词
HLA; immunopeptidome; Mascot; PEAKS; peptide splicing
资金
- Cancer Research UK [C67500, A29686]
- European Union's Horizon 2020 research and innovation programme [945528]
- European Research Council (ERC) [945528] Funding Source: European Research Council (ERC)
Unconventional epitopes are emerging targets for T cell immunotherapy, and mass spectrometry is commonly used for their identification. This study compared the performance of three database search engines and found that PEAKS DB showed better performance in identifying cis-spliced peptides and HLA class I immunopeptidomes.
Unconventional epitopes presented by HLA class I complexes are emerging targets for T cell targeted immunotherapies. Their identification by mass spectrometry (MS) required development of novel methods to cope with the large number of theoretical candidates. Methods to identify post-translationally spliced peptides led to a broad range of outcomes. We here investigated the impact of three common database search engines - that is, Mascot, Mascot+Percolator, and PEAKS DB - as final identification step, as well as the features of target database on the ability to correctly identify non-spliced and cis-spliced peptides. We used ground truth datasets measured by MS to benchmark methods' performance and extended the analysis to HLA class I immunopeptidomes. PEAKS DB showed better precision and recall of cis-spliced peptides and larger number of identified peptides in HLA class I immunopeptidomes than the other search engine strategies. The better performance of PEAKS DB appears to result from better discrimination between target and decoy hits and hence a more robust FDR estimation, and seems independent to peptide and spectrum features here investigated.
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