BamQuery: a proteogenomic tool for the genome-wide exploration of the immunopeptidome

Ruiz Cuevas, M. V.; Hardy, M.-P.; Larouche, J.-D.; Apavaloaei, A.; Kina, E.; Vincent, K.; Gendron, P.; Laverdure, J.-P.; Durette, C.; Thibault, P.; Lemieux, S.; Perreault, C.; Ehx, G.

doi:10.1101/2022.10.07.510944

bioRxiv · 10.1101/2022.10.07.510944

BamQuery: a proteogenomic tool for the genome-wide exploration of the immunopeptidome

Ruiz Cuevas, M. V.·Hardy, M.-P.·Larouche, J.-D.·Apavaloaei, A.·Kina, E.·Vincent, K.·Gendron, P.·Laverdure, J.-P.·Durette, C.·Thibault, P.·Lemieux, S.·Perreault, C.·Ehx, G.

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Abstract

MHC-I-associated peptides (MAPs) derive from selective yet highly diverse genomic regions, including allegedly non-protein-coding sequences, such as endogenous retroelements (EREs). Quantifying canonical (exonic) and non-canonical MAPs-encoding RNA expression in malignant and benign cells is critical for identifying tumor antigens (TAs) but represents a challenge for immunologists. We present BamQuery, a computational tool attributing an exhaustive RNA expression to MAPs of any origin (exon, intron, UTR, intergenic) from bulk and single-cell RNA-sequencing data. We show that non-canonical MAPs (including TAs) can derive from multiple different genomic regions (up to 35,343 for EREs), abundantly expressed in normal tissues. We also show that supposedly tumor-specific mutated MAPs, viral MAPs, and MAPs derived from proteasomal splicing can arise from different unmutated non-canonical genomic regions. The genome-wide approach of BamQuery allows comprehensive mapping of all MAPs in healthy and cancer tissues. BamQuery can also help predict MAP immunogenicity and identify safe and actionable TAs.

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Ruiz Cuevas, M. V., Hardy, M.-P., Larouche, J.-D., Apavaloaei, A., Kina, E., Vincent, K., Gendron, P., Laverdure, J.-P., Durette, C., Thibault, P., Lemieux, S., Perreault, C., Ehx, G.. 2022-10-08. BamQuery: a proteogenomic tool for the genome-wide exploration of the immunopeptidome. https://doi.org/10.1101/2022.10.07.510944

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