ProTrack: An Interactive Multi‐Omics Data Browser for Proteogenomic Studies

The Clinical Proteomic Tumor Analysis Consortium (CPTAC) initiative has generated extensive multi‐omics data resources of deep proteogenomic profiles for multiple cancer types. To enable the broader community of biological and medical researchers to intuitively query, explore, and download data and analysis results from various CPTAC projects, a prototype user‐friendly web application called “ProTrack” is built with the CPTAC clear cell renal cell carcinoma (ccRCC) data set (http://ccrcc.cptac-data-view.org). Here the salient features of this application which provides a dynamic, comprehensive, and granular visualization of the rich proteogenomic data is described.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163654/2/pmic13304.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163654/1/pmic13304_am.pd

ProTrack: An Interactive Multi‐Omics Data Browser for Proteogenomic Studies

The Clinical Proteomic Tumor Analysis Consortium (CPTAC) initiative has generated extensive multi‐omics data resources of deep proteogenomic profiles for multiple cancer types. To enable the broader community of biological and medical researchers to intuitively query, explore, and download data and analysis results from various CPTAC projects, a prototype user‐friendly web application called “ProTrack” is built with the CPTAC clear cell renal cell carcinoma (ccRCC) data set (http://ccrcc.cptac-data-view.org). Here the salient features of this application which provides a dynamic, comprehensive, and granular visualization of the rich proteogenomic data is described.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163654/2/pmic13304.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163654/1/pmic13304_am.pd

Pan-cancer proteogenomics connects oncogenic drivers to functional states

Cancer driver events refer to key genetic aberrations that drive oncogenesis; however, their exact molecular mechanisms remain insufficiently understood. Here, our multi-omics pan-cancer analysis uncovers insights into the impacts of cancer drivers by identifying their significant cis-effects and distal trans-effects quantified at the RNA, protein, and phosphoprotein levels. Salient observations include the association of point mutations and copy-number alterations with the rewiring of protein interaction networks, and notably, most cancer genes converge toward similar molecular states denoted by sequence-based kinase activity profiles. A correlation between predicted neoantigen burden and measured T cell infiltration suggests potential vulnerabilities for immunotherapies. Patterns of cancer hallmarks vary by polygenic protein abundance ranging from uniform to heterogeneous. Overall, our work demonstrates the value of comprehensive proteogenomics in understanding the functional states of oncogenic drivers and their links to cancer development, surpassing the limitations of studying individual cancer types

Proteogenomic insights into the biology and treatment of HPV-negative head and neck squamous cell carcinoma

We present a proteogenomic study of 108 human papilloma virus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). Proteomic analysis systematically catalogs HNSCC-associated proteins and phosphosites, prioritizes copy number drivers, and highlights an oncogenic role for RNA processing genes. Proteomic investigation of mutual exclusivity between FAT1 truncating mutations and 11q13.3 amplifications reveals dysregulated actin dynamics as a common functional consequence. Phosphoproteomics characterizes two modes of EGFR activation, suggesting a new strategy to stratify HNSCCs based on EGFR ligand abundance for effective treatment with inhibitory EGFR monoclonal antibodies. Widespread deletion of immune modulatory genes accounts for low immune infiltration in immune-cold tumors, whereas concordant upregulation of multiple immune checkpoint proteins may underlie resistance to anti-programmed cell death protein 1 monotherapy in immune-hot tumors. Multi-omic analysis identifies three molecular subtypes with high potential for treatment with CDK inhibitors, anti-EGFR antibody therapy, and immunotherapy, respectively. Altogether, proteogenomics provides a systematic framework to inform HNSCC biology and treatment.[Display omitted]•A systematic inventory of HNSCC-associated proteins, phosphosites, and pathways•Three multi-omic subtypes linked to targeted treatment approaches and immunotherapy•Widespread deletion of immune modulatory genes accounts for loss of immunogenicity•Two modes of EGFR activation inform response to anti-EGFR monoclonal antibodiesHuang et al. report a proteogenomic study on 108 HPV-negative head and neck squamous cell carcinomas (HNSCCs). In addition to creating a comprehensive resource for pathogenic insights, multi-omic analysis identifies therapeutic hypotheses that may inform more precise approaches to treatment