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  Database search engines and target database features impinge upon the identification of post‐translationally cis‐spliced peptides in HLA class I immunopeptidomes

Mishto, M., Horokhovskyi, Y., Cormican, J. A., Yang, X., Lynham, S., Urlaub, H., et al. (2022). Database search engines and target database features impinge upon the identification of post‐translationally cis‐spliced peptides in HLA class I immunopeptidomes. Proteomics, 22(10): e2100226. doi:10.1002/pmic.202100226.

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 Urheber:
Mishto, M., Autor
Horokhovskyi, Y.1, Autor           
Cormican, J. A.1, Autor           
Yang, X., Autor
Lynham, S., Autor
Urlaub, H.2, Autor           
Liepe, J.1, Autor           
Affiliations:
1Research Group of Quantitative and Systems Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350287              
2Research Group of Bioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350290              

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Schlagwörter: HLA; immunopeptidome; Mascot; PEAKS; peptide splicing
 Zusammenfassung: 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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Sprache(n): eng - English
 Datum: 2022-02-202022-05
 Publikationsstatus: Erschienen
 Seiten: -
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 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1002/pmic.202100226
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Projektname : The study was in part supported by: (i) MPI-BPC collaboration agreement 2018, Cancer Research UK (C67500; A29686) and National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas’ NHS Foundation Trust and King's College London and/or the NIHR Clinical Research Facility to MM; (ii) European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 945528) to JL. YH and JAC are supported by the International Max-Planck Research School (IMPRS) for Genome Science.
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Projektname : IMAP
Grant ID : 945528
Förderprogramm : Horizon 2020 (H2020)
Förderorganisation : European Commission (EC)

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Titel: Proteomics
Genre der Quelle: Zeitschrift
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Seiten: 16 Band / Heft: 22 (10) Artikelnummer: e2100226 Start- / Endseite: - Identifikator: -