PXD052187 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Integrating Machine Learning-Enhanced Immunopeptidomics and SARS-CoV-2 Population-Scale Analyses Unveils Novel Antigenic Features for Next-Generation COVID-19 Vaccines |
Description | Next-generation T-cell-directed vaccines for COVID-19 aim to induce durable T-cell immunity against circulating and future hypermutated SARS-CoV-2 variants. Mass Spectrometry (MS)based immunopeptidomics holds promise for guiding vaccine design, but computational challenges impede the precise and unbiased identification of conserved T-cell epitopes crucial for vaccines against rapidly mutating viruses. We introduce a computational framework and analysis platform integrating a novel machine learning algorithm, immunopeptidomics, intra-host data, epitope immunogenicity, and geo-temporal CD8+ T-cell epitope conservation analyses. Central to our approach is MHCvalidator, a novel artificial neural network algorithm enhancing MS-based immunopeptidomics sensitivity by modeling antigen presentation and sequence features. MHCvalidator identified a novel nonconventional SARS-CoV-2 T-cell epitope presented by B7 supertype molecules, originating from a +1-frameshift in a truncated Spike (S) antigen, supported by ribo-seq data. Intra-host analysis of SARS-CoV-2 proteomes from ~100,000 COVID-19 patients revealed a prevalent S antigen truncation in ~51% of cases, exposing a rich source of frameshifted viral antigens. Our framework includes EpiTrack, a new computational pipeline tracking global mutational dynamics of MHCvalidator-identified SARS-CoV-2 CD8+ epitopes from vaccine BNT162b4. While most vaccine-encoded CD8+ epitopes exhibit global conservation from January 2020 to October 2023, a highly immunodominant A*01-associated epitope, especially in hospitalized patients, undergoes substantial mutations in Delta and Omicron variants. Our approach unveils unprecedented SARS-CoV-2 T-cell epitopes, elucidates novel antigenic features, and underscores mutational dynamics of vaccine-relevant epitopes. The analysis platform is applicable to any viruses, and underscores the need for continual vigilance in T-cell vaccine development against the evolving landscape of hypermutating SARS-CoV-2 variants. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_07:01:58.010.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Saketh Kapoor |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Eclipse |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-05-10 14:26:15 | ID requested | |
1 | 2024-10-14 15:49:08 | announced | |
⏵ 2 | 2024-10-22 07:01:58 | announced | 2024-10-22: Updated project metadata. |
Publication List
Keyword List
submitter keyword: Immunopeptidomics, T-cell epitope, mass spectrometry, SARS-CoV-2, COVID-19, Next-gen vaccines |
Contact List
Etienne Caron |
contact affiliation | Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA |
contact email | etienne.caron@yale.edu |
lab head | |
Saketh Kapoor |
contact affiliation | Associate Research Scientist and Lab Manager |
contact email | saketh.kapoor@yale.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD052187
- Label: PRIDE project
- Name: Integrating Machine Learning-Enhanced Immunopeptidomics and SARS-CoV-2 Population-Scale Analyses Unveils Novel Antigenic Features for Next-Generation COVID-19 Vaccines