Project Summary – Core 4 – Genome Sequencing Core Dana-Farber Cancer Institute Whole genome sequencing especially at single cell level is a specialized function requiring expertise, special instruments and facilities along with informatics capabilities. This function cannot be performed in individual laboratories. Single cell sequencing is also evolving rapidly and constantly improving the information capabilities, number of samples per run and data modalities per cell. There is only limited number of facilities available worldwide with such capabilities to continue to innovate. Dana Farber/Harvard Cancer Center (DF/HCC) is a major center in the US sequencing significant number of cancer genomes. DFCI is committed to continually appraising new sequencing technologies, using in-house testing wherever possible, and will use whatever future technology is most suitable and cost-effective for the applications demanded by the science pursued at the Institute. The purpose of Core 4 is to provide for comprehensive genomic sequence analyses by utilizing a state of the art ‘next generation’ sequencing platform for the sequencing of whole genome, targeted regions, methylated regions, circulating cells as well as single cells and the identification and characterization of genome- wide somatic alterations in samples detailed in all projects. We have also developed and standardized single cell and bulk sequencing for various platforms. To meet these goals we will perform whole genome sequencing and enzymatic methylation sequencing to generate genome wide somatic alterations and methylation changes with streamlined analysis pipeline from IFM/DFCI 2009 and 2020-02 study samples at diagnosis and when available at relapse (Specific Aim 1); and generate single-cell whole genome and targeted sequencing data from selected serial samples to explore clonal changes during MM evolution (Specific Aim 2). Further, the core will provide bioinformatics expertise in the management and analysis of data produced within the core to support the projects.