THE CANCER CELL MAP INITIATIVE: A NATIONAL RESEARCH CENTER FOR CANCER SYSTEMS BIOLOGY OVERALL SUMMARY The Cancer Genome Atlas and sister projects have now completed analysis of over 10,000 tumor genomes, providing a catalog of the gene mutations, copy number variants and other genetic alterations that cause cancer. In many cases it remains unclear, however, which are the key driver mutations or dependencies in a given cancer and how these influence pathogenesis and response to therapy. Although tumors of similar types and clinical outcomes can have patterns of mutations that are strikingly different, it is becoming apparent that these mutations recurrently hijack the same hallmark molecular pathways and networks. For this reason, cancer research and treatment is increasingly dependent on knowledge of biological networks of multiple types, including physical interactions among proteins and syntheticlethal and epistatic interactions among genes. Here we seek support for a new effort, The Cancer Cell Map Initiative (CCMI), aimed at comprehensively detailing these complex interactions among cancer genes and proteins and how they differ between diseased and healthy states. The CCMI is a multicampus initiative of the University of California, centered at UC San Francisco and UC San Diego, which leverages advanced network mapping, computational analysis and cancer research platforms developed by multiple CCMI investigators over the past decade. Thus primed, these platforms will be turned to efficiently generate, assemble and analyze cancer molecular networks with a view towards pathway and networkbased personalized therapy. Specifically, over the next five years the CCMI will seek to catalyze major phase transitions in cancer research and therapy by (1) Comprehensively mapping the networks of physical interactions among cancer proteins, revealing the protein complexes and higherorder molecular units under selection in cancer; (2) Mapping the parallel networks of syntheticlethal and epistatic interactions among cancer genes, revealing the functional logic of cancer; (3) Establishing the robust computational methodology, enduser software, and databases for assembly and use of cancer cell network maps in both basic and clinical modalities; (4) Building a critical mass of leading cancer investigators worldwide to expand CCMI into a global coordinated partnership; and (5) Training the current and nextgeneration of scientists in Network Biology and its applications to cancer research.