ArticleMolecular & cellular proteomics : MCP2021
The Choice of Search Engine Affects Sequencing Depth and HLA Class I Allele-Specific Peptide Repertoires.
Article in Molecular & cellular proteomics : MCP, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Benchmarking Software for DDA-PASEF Immunopeptidomics.Molecular & cellular proteomics : MCP · 2026Article
- Sensitive detection of cancer antigens enabled by user-defined peptide libraries.Nature biotechnology · 2026Article
- PCI-DB: a novel primary tissue immunopeptidome database to guide next-generation peptide-based immunotherapy development.Journal for immunotherapy of cancer · 2025Article
- Maximizing Immunopeptidomics-Based Bacterial Epitope Discovery by Multiple Search Engines and Rescoring.Journal of proteome research · 2025Article
- A rapid ecologic analysis, confirmed by a case-control study, identifies class I HLA alleles correlated to the risk of COVID-19.Journal of translational medicine · 2025Article
- Integration of proteomics profiling data to facilitate discovery of cancer neoantigens: a survey.Briefings in bioinformatics · 2025Review
- Immunopeptidomics-based identification of naturally presented non-canonical circRNA-derived peptides.Nature communications · 2024Article
- Protein degradation by human 20S proteasomes elucidates the interplay between peptide hydrolysis and splicing.Nature communications · 2024Article
- MARS an improved de novo peptide candidate selection method for non-canonical antigen target discovery in cancer.Nature communications · 2024Article
- Deep Learning-Assisted Analysis of Immunopeptidomics Data.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Current perspectives on mass spectrometry-based immunopeptidomics: the computational angle to tumor antigen discovery.Journal for immunotherapy of cancer · 2023Review
- MSBooster: improving peptide identification rates using deep learning-based features.Nature communications · 2023Article
- Novel canonical and non-canonical viral antigens extend current targets for immunotherapy of HPV-driven cervical cancer.iScience · 2023Article
- Immunopeptidomics: Reading the Immune Signal That Defines Self From Nonself.Molecular & cellular proteomics : MCP · 2022Article
- Article
- T Cell Epitope Discovery in the Context of Distinct and Unique Indigenous HLA Profiles.Frontiers in immunology · 2022Review
- Immunopeptidogenomics: Harnessing RNA-Seq to Illuminate the Dark Immunopeptidome.Molecular & cellular proteomics : MCP · 2021Article
- Defining Spectral Quality in Mass Spectrometry-Based Proteomics: A Retrospective Review.Mass spectrometry reviewsReview
- Exploring the dynamic landscape of immunopeptidomics: Unravelling posttranslational modifications and navigating bioinformatics terrain.Mass spectrometry reviewsReview
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Standardization of immunopeptidomics experiments across laboratories is a pressing issue within the field, and currently a variety of different methods for sample preparation and data analysis tools are applied. Here, we compared different software packages to interrogate immunopeptidomics datasets and found that Peaks reproducibly reports substantially more peptide sequences (~30-70%) compared with Maxquant, Comet, and MS-GF+ at a global false discovery rate (FDR) of <1%. We noted that these differences are driven by search space and spectral ranking. Furthermore, we observed differences in the proportion of peptides binding the human leukocyte antigen (HLA) alleles present in the samples, indicating that sequence-related differences affected the performance of each tested engine. Utilizing data from single HLA allele expressing cell lines, we observed significant differences in amino acid frequency among the peptides reported, with a broadly higher representation of hydrophobic amino acids L, I, P, and V reported by Peaks. We validated these results using data generated with a synthetic library of 2000 HLA-associated peptides from four common HLA alleles with distinct anchor residues. Our investigation highlights that search engines create a bias in peptide sequence depth and peptide amino acid composition, and resulting data should be interpreted with caution.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.