Proteogenomics Shared Resource Summary Proteogenomics integrates now-readily-available next-generation DNA/RNA sequencing data with high- resolution mass spectrometry (MS)-based proteomics data to identify and quantify expressed proteins. As a Developing Shared Resource in the current funding period, Proteogenomics catalyzed numerous new collaborations, which allowed the development of new tools and workflows. It also contributed to several successful grant applications. In the current application, it is proposed as a New Shared Resource. In the coming funding period, we will continue to offer cutting-edge proteogenomic services to MCC members conducting basic, translational, and clinical cancer research, guided by these Specific Aims: 1) Offer customizable and flexible workflows for integrative, quantitative analysis of next-generation sequencing data and MS-based proteomics data to identify novel protein products underlying cancer; 2) Offer a complete informatics workflow for identifying and quantifying peptide neoantigens with promise for immuno-therapeutic applications; and 3) Offer validated and emerging metaproteomics tools and workflows for studies of microbiome contributions to cancer. The Proteogenomics Shared Resource is led by Director Dr. Tim Griffin (Genetic Mechanisms Program) and Coordinator Dr. Pratik Jagtap, who are leaders of the Galaxy for proteomics (Galaxy-P) project. Both have long track records in the application of proteogenomic and metaproteomic informatics to cancer research. We anticipate that 30 researchers, including 21 MCC members, will use this Resource each year. Access to the technologies offered by the Proteogenomics Shared Resource is free to users through the Minnesota Supercomputing Institute. Some support for staff members is requested to allow them to work with MCC members to design studies and generate preliminary data for grant applications.