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ABPEPserver: a web application for documentation and analysis of substitutants
Abhijeet Pataskar1, Jasmine Montenegro Navarro2, Reuven Agami3,4
1Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands. a.pataskar@nki.nl.
Background:
Cancer immunotherapy is implemented by identifying antigens that are presented on the cell surface of cancer cells and illicit T-cell response (Schumacher and Schreiber, Science 348:69-74, 2015; Waldman et al., Nat Rev Immunol 20:651-668, 2020; Zhang et al., Front Immunol 12:672,356, 2021b). Classical candidates of such antigens are the peptides resulting from genetic alterations and are named "neoantigen" (Schumacher and Schreiber, Science 348:69-74, 2015). Neoantigens have been widely catalogued across several human cancer types (Tan et al., Database (Oxford) 2020;2020b; Vigneron et al., Cancer Immun 13:15, 2013; Yi et al., iScience 24:103,107, 2021; Zhang et al., BMC Bioinformatics 22:40, 2021a). Recently, a new class of inducible antigens has been identified, namely Substitutants, that are produced as a result of aberrant protein translation (Pataskar et al., Nature 603:721-727, 2022). MAIN: Catalogues of Substitutant expression across human cancer types, their specificity and association to gene expression signatures remain elusive for the scientific community's access. As a solution, we present ABPEPserver, an online database and analytical platform that can visualize a large-scale tumour proteomics analysis of Substitutant expression across eight tumour types sourced from the CPTAC database (Edwards et al., J Proteome Res 14:2707-2713, 2015). Functionally, ABPEPserver offers the analysis of gene-association signatures of Substitutant peptides, a comparison of enrichment between tumour and tumour-adjacent normal tissues, and a list of peptides that serve as candidates for immunotherapy design. ABPEPserver will significantly enhance the exploration of aberrant protein production in human cancer, as exemplified in a case study.
Conclusion:
ABPEPserver is designed on an R SHINY platform to catalogue Substitutant peptides in human cancer. The application is available at https://rhpc.nki.nl/sites/shiny/ABPEP/ . The code is available under GNU General public license from GitHub ( https://github.com/jasminesmn/ABPEPserver ).
Insights
We introduce ABPEPserver, a new database for cataloguing Substitutant peptides in human cancers. This resource aids in identifying potential immunotherapy targets by analyzing aberrant protein expression and its association with gene signatures.
Area of Science:
- Oncology
- Immunology
- Bioinformatics
- Proteomics
Background:
- Cancer immunotherapy relies on identifying cell surface antigens to elicit T-cell responses.
- Neoantigens, derived from genetic alterations, are classical targets, but a new class, Substitutants, arising from aberrant protein translation, are emerging.
- Catalogues of Substitutant expression, specificity, and gene associations in human cancers are currently limited.
Purpose of the Study:
- To present ABPEPserver, an online database and analytical platform for visualizing Substitutant expression in human cancers.
- To provide tools for analyzing gene-association signatures of Substitutant peptides.
- To facilitate the comparison of Substitutant enrichment between tumor and normal tissues and identify immunotherapy candidates.
Main Methods:
- Developed ABPEPserver on an R Shiny platform.
- Integrated large-scale tumor proteomics data from the CPTAC database across eight tumor types.
- Implemented analytical functions for gene-association signatures, tissue comparisons, and candidate peptide identification.
Main Results:
- ABPEPserver provides a comprehensive catalog of Substitutant peptides across eight human cancer types.
- The platform enables analysis of Substitutant peptide-gene associations and their differential expression in tumors versus normal tissues.
- Identified candidate Substitutant peptides for potential immunotherapy design.
Conclusions:
- ABPEPserver is a valuable resource for exploring aberrant protein production in human cancer.
- The platform enhances the discovery of novel cancer antigens for immunotherapy development.
- ABPEPserver is accessible online with its code available under a GNU General Public License.
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