Abstract 4106: Curating protein complexes from multiple resources and validate their co-regulations at RNA/protein level in pan-cancer

Abstract Protein complexes are sets of proteins that not only physically interact with each other, but also play important roles in progression of diseases like cancer. However, little is known about the co-regulation patterns of complexes and how many of them could be potential therapeutic targets. We collected 16,680 complexes from CORUM, Reactome, Complex Portal, and Havugimana PC. Harmonization of subunits of complexes by UniProt ID removed 4,112 redundant complexes. We further found that 3,018/12,559 complexes have at least one cancer driver gene involved, of which 2,408 complexes were found to have druggable genes, according to CiVic and OncoKB. Co-regulation patterns of 12,559 complexes were annotated utilizing gene expression and protein expression data from 1,101 cases across 10 cancer types (BR, COAD, OV, UCEC, HNSCC, PDAC, LSCC, LUAD, GBM, and ccRCC) from the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Pairwise correlations across subunits of each complex at protein and RNA levels were calculated separately. Correlation >0.8 would suggest strong interaction of the subunits of the complex. Protein-only co-regulation complex was declared for protein pairwise correlation >0.8 and RNA pairwise correlation <0.5. RNA-only co-regulation complex was defined vice versa. We found more protein-only co-regulation complexes than RNA-only co-regulation complexes. This validated that RNA expression doesn’t always correlate with protein expression and few complexes were co-regulated at both RNA and protein levels. Our study suggests the value of utilizing proteome data to understand the formation of complex and inner relationships between subunits of complexes. Citation Format: Yizhe Song, Daniel Cui Zhou, Yize Li, Liang-Bo Wang, Michael C. Wendl, Gad Getz, Li Ding. Curating protein complexes from multiple resources and validate their co-regulations at RNA/protein level in pan-cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4106.