Multi-Scale Mapping Of The Physical And Functional Architecture Of The Cancer Cell

Cancer is governed by modular systems of genes, the composition and organization of which remains poorly understood. Here, we integrate physical and functional networks from a wide range of molecular studies to assemble a comprehensive multi-scale map of human cancer cell biology. This map consists of a hierarchical catalog of protein complexes, signaling pathways and inter-pathway crosstalk implicated in cancer, and it suggests many uncharacterized functional modules as intriguing hypotheses for further validation. Analysis of the pattern of somatic mutations in The Cancer Genome Atlas (TCGA) reveals that these mutations target systems of varying scales above the level of individual genes. The map also provides a platform to integrate and interpret new 9omics data; we integrate new protein-protein interactions identified using AP-MS in multiple breast cancer cell lines, revealing how different functional modules are rewired in cancer cells. A general model browsing tool has been created to visualize and navigate these hierarchical cancer maps. This multi-scale mapping approach elucidates the molecular heterogeneity of cancer, connects tumor genotypes to phenotypes and, ultimately, enables a platform for cancer precision medicine. Citation Format: Fan Zheng, Michael K. Yu, Minkyu Kim, Keiichiro Ono, Mitchell Flagg, Jason F. Kreisberg, Nevan Krogan, Trey Ideker. Multi-scale mapping of the physical and functional architecture of the cancer cell [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1317.