PXD052187-2

PXD052187 is an original dataset announced via ProteomeXchange.

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

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.

10.21203/RS.3.RS-3914861/V1;

submitter keyword: Immunopeptidomics, T-cell epitope, mass spectrometry, SARS-CoV-2, COVID-19, Next-gen vaccines

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/10/PXD052187

PRIDE project URI

• PRIDE
  1. PXD052187
     1. Label: PRIDE project
     2. Name: Integrating Machine Learning-Enhanced Immunopeptidomics and SARS-CoV-2 Population-Scale Analyses Unveils Novel Antigenic Features for Next-Generation COVID-19 Vaccines