An Integrated Approach for Discovering Noncanonical MHC-I Peptides Encoded by Small Open Reading Frames
peer-reviewed · Journal of the American Society for Mass Spectrometry · 2021
| Date | 2021-09-01 |
| Type | peer-reviewed |
| Venue | Journal of the American Society for Mass Spectrometry |
| Publisher | American Chemical Society (ACS) |
| Contribution | downstream-application |
| DOI | 10.1021/jasms.1c00076 |
| Citations (OpenAlex) | 19 |
| Venue 2-year citedness | 2.84 |
Abstract
MHC-I peptides are a group of important immunopeptides presented by major histocompatibility complex (MHC) on the cell surface for immune recognition. The majority of reported MHC-I peptides are derived from protein coding sequences, and noncanonical peptides translated from small open reading frames (sORF) are largely unknown due to the lack of accurate and sensitive detection methods. Herein we report an efficient approach that implements complementary bioinformatic strategies to improve the identification of noncanonical MHC-I peptides. In a database search strategy, noncanonical immunopeptides mapping was optimized by combining three complementary pipelines to construct predicted sORF databases from Ribo-seq data. In a de novo peptide sequencing strategy, MS data search results were filtered against sORF databases to pin down additional noncanonical immunopeptides. In total, 308 noncanonical immunopeptides were identified from two tumor cell lines with selected ones vigorously validated. Our approach is a handy solution to identify noncanonical MHC peptides with Ribo-seq and MS data. Meanwhile, the novel noncanonical immunopeptides identified with this method could shed insights on fundamental immunology as well as cancer immunotherapies.
Methods and tools
- sORF noncanonical MHC-I peptides: Combines Ribo-seq-derived sORF databases with database search and de novo sequencing to identify 308 noncanonical MHC class I peptides from two tumor cell lines.
Data deposited
- Discovery of Non-Canonical Peptides Derived from Novel Small Open Reading Frames as MHC-I Epitopes (as deposited) · PXD024415
Cites (4)
- Peptidomes and Structures Illustrate Two Distinguishing Mechanisms of Alternating the Peptide Plasticity Caused by Swine MHC Class I Micropolymorphism (2021) crossref
- Personalized deep learning of individual immunopeptidomes to identify neoantigens for cancer vaccines (2020) crossref
- Uncovering Thousands of New Peptides with Sequence-Mask-Search Hybrid De Novo Peptide Sequencing Framework (2019) crossref
- Constrained De Novo Sequencing of neo-Epitope Peptides Using Tandem Mass Spectrometry (2018) crossref