MAPDP: A Cloud-Based Computational Platform for Immunopeptidomics Analyses

The immunopeptidome corresponds to
the repertoire of peptides presented
at the cell surface by the major histocompatibility complex (MHC)
molecules. Cytotoxic T cells scan this repertoire to identify nonself
antigens that can arise from tumors or infected cells. The identification
of actionable antigenic targets is key to the development of therapeutic
cancer vaccines, T-cell therapy, and other T-cell receptor-based biologics.
The growing clinical interest for immunopeptidomics has accelerated
the development of high throughput proteogenomic platforms that provide
a system-level analysis of MHC-associated peptides. Improvement in
sensitivity and throughput of mass spectrometers now allows the detection
of a few thousands of peptides from less than 100 million cells. To
manage the amount of data generated by these instruments, we have
developed the MHC-associated peptide discovery platform (MAPDP), a
novel open-source cloud-based computational platform for immunopeptidomic
analyses. It provides convenient access from a web portal to immunopeptidomes
stored in the database, filtering tools, various visualizations, annotations
(e.g., IEDB, dbSNP, gnomAD), peptide-binding affinity prediction (mhcflurry,
NetMHC), HLA genotyping, and the generation of personalized proteome
databases. MAPDP functionalities are demonstrated here by the discovery
of MHC peptides featuring new genetic variants identified in two previously
published ovarian carcinoma data sets.