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The cryptic immunopeptidome in health and disease.
Trends Genet
October 2024
Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, Canada. Electronic address:
Article Synopsis
- Peptides associated with MHC proteins play a crucial role in regulating T cell functions, creating a complex called the immunopeptidome, which is pivotal for T cell biology.
- * Recent advancements in mass spectrometry and next-generation sequencing have significantly impacted the emerging field of immunopeptidomics, allowing for deeper analysis of these peptide profiles.
- * The article highlights the "cryptic" immunopeptidome, which involves peptides from unconventional open reading frames and is primarily derived from unstable proteins in various cell types, including cancer cells, where many specific MAPs are identified as cryptic.
High-quality peptide evidence for annotating non-canonical open reading frames as human proteins.
bioRxiv
September 2024
Princess Máxima Center for Pediatric Oncology, Utrecht, 3584 CS, The Netherlands.
Article Synopsis
- Researchers aim to better understand the protein-coding genome due to its importance in human health, while questioning what previous genomic studies may have overlooked regarding non-canonical open reading frames (ncORFs).
- Over the last ten years, ncORFs have shown potential relevance in human cell types and diseases, but their impact on the human proteome was previously unclear, prompting a collaborative effort to analyze their protein-level evidence.
- The study found that 25% of analyzed ncORFs contribute to translated proteins, resulting in over 3,000 new peptides from extensive mass spectrometry data, and established an annotation framework and public tools to support ongoing research in this area.
Article Synopsis
- Researchers have found that microproteins from noncanonical open reading frames (ncORFs) can produce tumor-specific antigens during cancer progression, potentially triggering immune responses.
- By analyzing RNA sequencing and other data from 117 liver cancer (hepatocellular carcinoma) tumors, they discovered that about 40% of these antigens likely come from ncORFs, including some that can initiate an immune response in humanized mice.
- The study also identified 33 long noncoding RNAs that express shared cancer antigens found in over 10% of the samples, suggesting new possibilities for developing cancer vaccines.
The HLA-II immunopeptidome of SARS-CoV-2.
Cell Rep
January 2024
Broad Institute of MIT and Harvard University, Cambridge, MA, USA; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA; Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA; Department of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Targeted synthetic vaccines have the potential to transform our response to viral outbreaks, yet the design of these vaccines requires a comprehensive knowledge of viral immunogens. Here, we report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peptides that are naturally processed and loaded onto human leukocyte antigen-II (HLA-II) complexes in infected cells. We identify over 500 unique viral peptides from canonical proteins as well as from overlapping internal open reading frames.
View Article and Find Full Text PDFMachine learning-based peptide-spectrum match rescoring opens up the immunopeptidome.
Proteomics
April 2024
Laboratory of Protein Science, Proteomics and Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Immunopeptidomics is a key technology in the discovery of targets for immunotherapy and vaccine development. However, identifying immunopeptides remains challenging due to their non-tryptic nature, which results in distinct spectral characteristics. Moreover, the absence of strict digestion rules leads to extensive search spaces, further amplified by the incorporation of somatic mutations, pathogen genomes, unannotated open reading frames, and post-translational modifications.
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