Workflow enabling deepscale immunopeptidome, proteome, ubiquitylome, phosphoproteome, and acetylome analyses of sample-limited tissues
Year: 2023
Type: article
Abstract: Serial multi-omic analysis of proteome, phosphoproteome, and acetylome provides insights into changes in protein expression, cell signaling, cross-talk and epigenetic pathways involved in disease pathology and treatment. However, ubiquitylome and HLA peptidome data collection used to understand protein degradation and antigen presentation have not together been serialized, and instead require separate samples for parallel processing using distinct protocols. Here we present MONTE, a highly sensitive multi-omic native tissue enrichment workflow, that enables serial, deep-scale analysis of HLA-I and HLA-II immunopeptidome, ubiquitylome, proteome, phosphoproteome, and acetylome from the same tissue sample. We demonstrate that the depth of coverage and quantitative precision of each 'ome is not compromised by serialization, and the addition of HLA immunopeptidomics enables the identification of peptides derived from cancer/testis antigens and patient specific neoantigens. We evaluate the technical feasibility of the MONTE workflow using a small cohort of patient lung adenocarcinoma tumors.
Source: Nature Communications
Authors: Jennifer G. Abelin, Erik J. Bergstrom, Keith D. Rivera, Hannah B. Taylor, Susan Klaeger, Charles Xu, Eva K. Verzani, C. Jackson White, Hilina B. Woldemichael, Maya Virshup, Meagan E. Olive, Myranda Maynard, Stephanie A. Vartany, Joseph D. Allen, Kshiti Phulphagar, M. Harry Kane, Suzanna Rachimi, D. R. Mani, Michael A. Gillette, Shankha Satpathy, Karl R. Clauser, Namrata D. Udeshi, Steven A. Carr
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $6,290
Funders: National Science Foundation, U.S. Department of Health and Human Services, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, Broad Institute, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Scheme for Promotion of Academic and Research Collaboration, National Institutes of Health, National Cancer Institute
Awards: G1058325490, G1164479764, G1777478423, Deciphering and Targeting the Cancer Ubiquitylome, Center of Excellence for High Throughput Proteogenomic Characterization, G335919598, G7159334849, Proteogenomic Predictors of Recurrence in Non-small Cell Lung Cancer, Center for comprehensive proteogenomic data analysis, Comprehensive dissection of the CLL genome & phenome to improve patient outcomes
OpenAlex ID: W4362522757