PROJECT SUMMARY – Molecular Genomics Shared Resource The mission of the Molecular Genomics (MGC) Shared Resource (SR) of the USC Norris Comprehensive Cancer Center (NCCC) is to provide services for industry-standard and state-of-the-art molecular and genomic assays in support of NCCC investigators working across the continuum of basic, translational, clinical, and population sciences. Overseen by NCCC Administration and under the leadership of John Carpten PhD and David Craig PhD, both newly recruited to NCCC in the current cycle, the MGC serves as a foundational element with industry- standard technologies and field-leading expertise in large-scale SNP genotyping, DNA methylation arrays, integrated genomic sequencing at the somatic, transcriptomic, and epigenetic landscape as well as state-of-the- art single-cell and spatial molecular profiling. Major developments this cycle include access to larger production- scale sequencing, ensuring early access to transformative emerging technologies, and implementation of bioinformatic processes integration into other SRs. Specifically, MGC: 1) added a high-throughput sequencing arm built from the ground up with advanced robotics and Illumina NovaSeq to enable large-scale projects; 2) established new collaborations with industry partners to ensure availability and early access to advanced state- of-the-art single-cell and spatial molecular profiling, including 10X Genomics, Agilent, and Nanostring; and 3) implemented automated APIs, bioinformatics, and data processing for tight coordination with the Data Science Shared Resource (DSC) in large-scale Novaseq sequencing. In alignment with the NCCC Strategic Plan, in the next grant cycle, MGC plans to perform comprehensive molecular profiling with linkage to curated patient data, including single-cell genomics, liquid biopsies for screening and residual disease, and imaging mass cytometry and spatial transcriptomics to capture tumor and tumor microenvironment interactions applied to NCCC's diverse patient population. During the current grant period (2015-2020), 122 NCCC members representing all five programs utilized the MGC, resulting in 233 publications and $58.4M in direct cost grant funding as a direct result of usage. The anticipated annual budget of the MGC in the first year of the next grant cycle is $2,875,229, yet the CCSG request is $457,972. Accordingly, the MGC leverages extensive institutional and recharge support and seeks only 16% from CCSG funds.