Ontology highlight
ABSTRACT:
PROVIDER: PRJNA721129 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14206078_1.fastq.gz | Fastqsanger.gz | |||
| SRR14206078_2.fastq.gz | Fastqsanger.gz | |||
| SRR14206079_1.fastq.gz | Fastqsanger.gz | |||
| SRR14206079_2.fastq.gz | Fastqsanger.gz | |||
| SRR14206080_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:The identification of peptides presented by HLA class I molecules to CD8+ T cells – i.e. the HLA-I immunopeptidome - is a useful tool to fish epitopes suitable for vaccinations and immunotherapies against cancer, infection and autoimmunity. These peptides are mainly generated by proteasomes through peptide hydrolysis and peptide splicing. Post-translationally spliced epitopes can enlarge the antigenic landscape and thus immunotherapy efficacy. Their identification is challenging, and the few methods proposed so far hinted toward a controversial broad spectrum of cis-spliced peptide frequencies in HLA-I immunopeptidomes. We here developed a new method named SPI-ART, which can identify cis-spliced peptides in HLA-I immunopeptidomes with precision and recall outperforming all other methods. The benchmark of the methods’ performances provided the proper analytical framework to explain the discordant results published so far. It also allowed to estimate the frequency of cis-spliced peptides in HLA-I immunopeptidomes, and to shed light on the biochemistry of these unconventional peptides and their potential antigenicity.
2022-08-12 | PXD025346 | Pride
Project description:Unconventional epitopes presented by HLA class I complexes are emerging targets for T cell targeted immunotherapies. Their identification by mass spectrometry 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 – i.e. 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 mass spectrometry 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. Head of the research group Molecular Immunology at King’s College London and the Francis Crick Institute, London (UK). Email: michele.mishto@kcl.ac.uk,
2022-04-06 | PXD031709 | Pride
Project description:The diversity of peptides displayed by class I HLA plays an essential role in T cell immunity. The peptide repertoire is extended by various post-translational modifications, including cis-splicing of peptides from the same protein. Here, we have applied a novel bioinformatic workflow and demonstrate that spliced-peptides are also generated through trans-splicing (fusion of peptide segments from distinct antigens) and their abundance challenges current models of proteasomal-splicing that predict cis-splicing as the most probable outcome. These trans-spliced peptides display canonical HLA binding motif sequence features. These results highlight the unanticipated diversity of the immunopeptidome and have important implications for autoimmunity, vaccine design and immunotherapy.
2021-12-06 | PXD017922 | Pride
Project description:The diversity of peptides displayed by class I HLA plays an essential role in T cell immunity. The peptide repertoire is extended by various post-translational modifications, including cis-splicing of peptides from the same protein. Here, we have applied a novel bioinformatic workflow and demonstrate that spliced-peptides are also generated through trans-splicing (fusion of peptide segments from distinct antigens) and their abundance challenges current models of proteasomal-splicing that predict cis-splicing as the most probable outcome. These trans-spliced peptides display canonical HLA binding motif sequence features. These results highlight the unanticipated diversity of the immunopeptidome and have important implications for autoimmunity, vaccine design and immunotherapy.
2018-10-16 | PXD009660 | Pride
Project description:Post translational spliced peptides bound to the HLA are unique type of peptides, shown in cancer, for HLA-class-I. Thus far, no consensus has been reached on the extent to which post-translational spliced peptides (PTSPs) occur, stirring significant debate. Furthermore, the role of the HLA-class-II pathway has been studied only in diabetes. Here, we exploit our large-scale cancer peptidomics database and devise a pipeline to filter spliced peptide predictions, to identify recurring spliced peptides, both for HLA-class-I and -II. Our results indicate that HLA-Class-I spliced peptides account for a low percentage (4.4%) of the immunopeptidome, yet are larger in number relative to other types of identified aberrant peptides. Therefore, spliced peptides contribute significantly to the repertoire of presented peptides in cancer cells. In addition, HLA-class-II bound spliced peptides were identified as well, but to a lower extent (0.6%).
2023-05-10 | PXD034788 | Pride
Project description:Proteasomes catalyze the degradation of endogenous proteins into oligopeptides, but can concurrently create spliced oligopeptides through ligation of previously non-contiguous peptide fragments. Recent studies have uncovered a formerly unappreciated role for proteasome-catalyzed peptide splicing (PCPS) in the generation of non-genomically templated human leukocyte antigen class I (HLA-I)-bound cis-spliced peptides that can be targeted by CD8+ T cells in cancer and infection. However, the mechanisms defining PCPS reactions are poorly understood. Here, we experimentally define the biochemical constraints of proteasome-catalyzed cis-splicing reactions by examination of in vitro proteasomal digests of a panel of viral- and self-derived polypeptide substrates using a tailored mass-spectrometry-based de novo sequencing workflow. We show that forward and reverse PCPS reactions display unique splicing signatures, defined by preferential fusion of distinct amino acid residues with stringent peptide length distributions, suggesting sequence- and size-dependent accessibility of splice reactants for proteasomal substrate binding pockets. Our data provide the basis for a more informed mechanistic understanding of PCPS
2021-05-17 | PXD025893 | Pride
Project description:Peptides generated by proteasome-catalyzed splicing of non-contiguous amino acid sequences have been shown to constitute a source of non-templated human leukocyte antigen class I (HLA-I) epitopes, but their role in pathogen-specific immunity remains unknown. CD8+ T cells are key mediators of human immunodeficiency virus type 1 (HIV-1) control, and identification of novel epitopes to enhance targeting of infected cells is a priority for prophylactic and therapeutic strategies. To explore the contribution of proteasome-catalyzed peptide splicing (PCPS) to HIV-1 epitope generation, we developed a broadly-applicable mass spectrometry-based discovery workflow that we employed to identify spliced HLA-I-bound peptides on HIV-infected cells. We demonstrate that HIV-1-derived spliced peptides comprise a novel, but relatively minor, component of the HLA-I-bound viral immunopeptidome. Although spliced HIV-1 peptides may elicit CD8+ T cell responses relatively infrequently during infection, CD8+ T cells primed by partially-overlapping contiguous epitopes in HIV-infected individuals were able to cross-recognize spliced viral peptides, suggesting a potential role for PCPS in restricting HIV-1 escape pathways. Vaccine-mediated priming of responses to spliced HIV-1 epitopes could thus provide a novel means of exploiting epitope targets typically under-utilized during natural infection.
2019-11-25 | PXD015489 | Pride
Project description:Prediction of HLA epitopes is important for the development of cancer immunotherapies and vaccines. However, current prediction algorithms have limited predictive power, in part because they were not trained on high-quality epitope datasets covering a broad range of HLA alleles. To enable prediction of endogenous HLA class I-associated peptides across a large fraction of the human population, we used mass spectrometry to profile >185,000 peptides eluted from 95 HLA-A, -B, -C and -G mono-allelic cell lines. We identified canonical peptide motifs per HLA allele, unique and shared binding submotifs across alleles and distinct motifs associated with different peptide lengths. By integrating these data with transcript abundance and peptide processing, we developed HLAthena, providing allele-and-length-specific and pan-allele-pan-length prediction models for endogenous peptide presentation. These models predicted endogenous HLA class I-associated ligands with 1.5-fold improvement in positive predictive value compared with existing tools and correctly identified >75% of HLA-bound peptides that were observed experimentally in 11 patient-derived tumor cell lines.
2019-12-16 | GSE131267 | GEO
Project description:Proteasomes catalyse the degradation of endogenous proteins into oligopeptides, but can concurrently create spliced oligopeptides through ligation of previously non-contiguous peptide fragments. Recent studies have uncovered a formerly unappreciated role for proteasome-catalysed peptide splicing (PCPS) in the generation of non-genomically templated major histocompatibility complex class I (MHC-I)-bound cis-spliced peptides that can be targeted by CD8+ T cells in cancer and infection. However, the mechanisms defining PCPS reactions are poorly understood. Here, we experimentally define the biochemical constraints of proteasome-catalysed cis-splicing reactions by examination of in vitro proteasomal digests of a panel of viral and self-derived polypeptide substrates using a tailored mass-spectrometry-based de novo sequencing workflow. We show that forward and reverse PCPS reactions display unique splicing signatures, defined by preferential fusion of distinct amino acid residues with stringent peptide length distributions, suggesting sequence- and size-dependent accessibility of splice reactants for proteasomal substrate binding pockets. Our data provide the basis for a more informed mechanistic understanding of PCPS that will facilitate future prediction of spliced peptides from protein sequences.
2020-10-26 | PXD021339 | Pride
Project description:LC-MS/MS-based identification of HLA-peptides is poised to provide a deep understanding of the rules underlying antigen presentation. However, a key obstacle limiting the utility of MS data is the ambiguity arising from the co-expression of multiple HLA alleles. Here, we introduce a strategy for profiling the HLA ligandome one allele at a time. By using cell lines expressing a single HLA allele, optimizing immunopurifications, and developing a novel spectral search algorithm, we identified thousands of peptides bound to 16 different HLA class I alleles. These data enabled the discovery of novel binding motifs, and an integrative analysis quantifying the contribution of factors critical to epitope presentation, such as protein cleavage and gene expression. We trained neural network prediction algorithms with our large dataset (>24,000 peptides) and outperformed algorithms trained on datasets of peptides with measured affinities. We thus demonstrate a scalable strategy for systematically learning the rules of endogenous antigen presentation.
2017-02-21 | GSE93315 | GEO