A. Objectives The New York Genome Center (NYGC) CORE 2.0 aims to lend NYGC’s significant sequencing capacity and experience generating large-scale, high-quality, sequencing data to TOPMed’s aim to continue generating genomics data for studies seeking to discover risk factors influencing heart, lung, blood, and sleep disorders. We are prepared to support 1) Task Area 2a: Whole Genome Sequencing (WGS) using state of the art technologies, 2) Task Area 2b: RNA paired-end 100bp sequencing; 3) Task Area 5: various single-cell and single-nuclei assays and spatial transcriptomics. Genome wide methylation profiling using the Illumina methylationEPIC array will be included in Task Area 2a. NYGC has a proven track record of delivering high quality ‘omic’ sequence data at scale through our participation in large consortia and programs, including: A) NHLBI’s TOPMed program as a Centralized Omics REsource (CORE) to which we contributed deep sequencing for 6,500 whole genomes, and delivery of 9,500 RNA samples while currently in the process of sequencing and delivering 12,800 more B) NHGRI’s Center for Common Disease Genetics grant for which we have sequenced ~40,000 genomes, and C) NYGC is currently serving as an NCI Genomic Characterization Center, sequencing Smart-Seq2 and 10X Genomics single cell libraries for NCI’s Project HOPE and Project GBM CARE as well as genomic characterization by DNA Methylation Array for the Center for Cancer Genomics (CCG). NYGC was additionally awarded two NCI GCC subcontracts from Leidos Biomedical Research, Inc. as part of the MP2PRT Program for over 900 FFPE tumor-normal whole genomes. Most recently NYGC has been awarded 1) a large ID/IQ contract with a value of up to ~$73M over 5 years to serve as a sequencing core for the NIH Brain Initiative Cell Atlas Network (BICAN); and 2) a $3M two-year grant to serve as Genomic Characterization Center for the NIH Common Fund’s Somatic Mosaicism Across Human Tissues (SMaHT) program, for which we will use whole genome short read sequencing, RNA sequencing and long read genome sequencing to characterize somatic mutations in healthy human tissues.