PXD040265

PXD040265 is an original dataset announced via ProteomeXchange.

Title	Using long-read CAGE sequencing to profile cryptic-promoter derived transcripts and their contribution to the immunopeptidome
Description	Recent studies have demonstrated that the non-coding genome can produce unannotated proteins as antigens that induce immune response. One major source of this activity is the aberrant epigenetic reactivation of transposable elements (TEs). In tumors, TEs often provide cryptic or alternate promoters, which can generate transcripts that encode tumor-specific unannotated proteins. Thus, TE-derived transcripts have the potential to produce tumor-specific, but recurrent, antigens shared among many tumors. Identification of TE-derived tumor antigens holds the promise to improve cancer immunotherapy approaches; however, current genomics and computational tools are not optimized for their detection. Here we combined CAGE technology with full-length long-read transcriptome sequencing (Long-Read CAGE, or LRCAGE) and developed a suite of computational tools to significantly improve immunopeptidome detection by incorporating TE-derived and other tumor transcripts into the proteome database. By applying our methods to human lung cancer cell line H1299 data, we demonstrated that long-read technology significantly improves mapping of promoters with low mappability scores and LRCAGE guarantees accurate construction of uncharacterized 5’ transcript structure. Unannotated peptides predicted from newly characterized transcripts were readily detectable in whole cell lysate mass-spectrometry data. Incorporating unannotated peptides into the proteome database enabled us to detect non-canonical antigens in HLA-pulldown LC-MS/MS data. At last, we showed that epigenetic treatment increased the number of non-canonical antigens, particularly those encoded by TE-derived transcripts, which might expand the pool of targetable antigens for cancers with low mutational burden.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:03:46.971.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ju Heon Maeng
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-20 05:00:22	ID requested
1	2023-09-23 08:45:07	announced
⏵ 2	2024-10-22 06:03:47	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: antigens, immunotherapy, epigenetic treatment,transposable elements, long-read sequencing

Ting Wang
contact affiliation	Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA;Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA;McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA
contact email	twang@wustl.edu
lab head
Ju Heon Maeng
contact affiliation	Washington University in St. Louis
contact email	j.maeng@wustl.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/2023/09/PXD040265

PRIDE project URI

• PRIDE
  1. PXD040265
     1. Label: PRIDE project
     2. Name: Using long-read CAGE sequencing to profile cryptic-promoter derived transcripts and their contribution to the immunopeptidome