AUTHOR=Singh Sasha A. , Kuraoka Shiori , Pestana Diego Vinicius Santinelli , Nasir Waqas , Delanghe Bernard , Aikawa Masanori TITLE=The RiboMaP Spectral Annotation Method Applied to Various ADP-Ribosylome Studies Including INF-γ-Stimulated Human Cells and Mouse Tissues JOURNAL=Frontiers in Cardiovascular Medicine VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.851351 DOI=10.3389/fcvm.2022.851351 ISSN=2297-055X ABSTRACT=

ADP-ribosylation is a post-translational modification that is catalyzed by the ADP-ribosyltransferase enzyme family. Major emphasis to date has been ADP-ribosylation's role in cancer; however, there is growing interest in its role in inflammation and cardiovascular disease. Despite a recent boom in ADP-ribosylation mass spectrometry-based proteomics, there are limited computational resources to evaluate the quality of reported ADP-ribosylated (ADPr) proteins. We recently developed a novel mass spectral annotation strategy (RiboMaP) that facilitates identification and reporting of ADPr peptides and proteins. This strategy can monitor the fragmentation properties of ADPr peptide-unique fragment ions, termed m-ions and p-ions, that in turn provide spectral quality scores for candidate ADP-ribosyl peptides. In this study, we leveraged the availability of publicly available ADP-ribosylome data, acquired on various mass spectrometers, to evaluate the broader applicability of RiboMaP. We observed that fragmentation spectra of ADPr peptides vary considerably across datasets; nonetheless, RiboMaP improves ADPr peptide spectral annotation across all studies. We then reanalyzed our own previously published in vitro ADP-ribosylome data to determine common responses to the pro-inflammatory cytokine, IFN-γ. We conclude that despite these recent advances in the field of ADPr proteomics, studies in the context of inflammation and cardiovascular disease still require further bench-to-informatics workflow development in order to capture ADPr signaling events related to inflammatory pathways.