The goal of the Northwest Genomics Center for All of Us (NWGC) is to provide high-throughput genotyping and whole genome sequencing (WGS) for individuals enrolled in the All of Us Research Program using a highly successful pipeline that has produced genotyping on nearly two hundred thousand samples and tens of thousands of high quality human genomes. The Northwest Genomics Center brings together three internationally recognized PIs (Nickerson (Contact), Eichler, and Jarvik), with decades of expertise in high-throughput clinical genomics and, together with their Co-Investigators, have returned tens of thousands of variant interpretations to patients. As we have done in the past with other NIH programs, we will coordinate our efforts with the All of Us program team in the National Center for Advancing Translational Sciences (NCATS), the other centers in the program such as the Data and Research Center (DRC) and the Biobank, and other Genome Centers if selected. To advance the goals and objectives of the All of Us Research Program we will produce and interpret variants from genotyping arrays for up to 100,000 samples in year 1 and up to 200,000 samples in years 2 - 5. We will also produce and interpret variants on more than 10,000 samples by WGS in year 1; up to 100,000 samples in year 2; and up to 200,000 samples in years 3-5 using the Illumina NovaSeq platform. To accomplish this, we will: 1- Work with the All of Us program, the DRC, the Biobank, and other groups to deliver an efficient and effective process for evaluating and completing high-throughput genotyping and WGS, call variants, and interpret the impact of variants in the ACMG 59 genes and other genes as indicated by the program in a CLIA-certified environment. 2- Interact directly with the Biobank to carefully develop the logistics and methods for preparing and receiving samples. 3- Track all samples and data transfers for all samples at every stage of the process (from project initiation to data delivery using our secure, completely interactive, and integrated laboratory information management system (LIMS)) and provide reports to the program, the DRC, and other groups as required. 4- Provide genotype and WGS data of the highest quality, in formats required by the program such as IDAT files for genotyping and CRAMs and VCFs for WGS. 5- Provide a team of specialized personnel and staff versed in the workflow of a well-established high-throughput CLIA-certified genome center. These include individuals specifically trained in DNA sample receipt, quality control, and large-scale bioinformatics analysis and variant interpretation. 6- Assist as needed with additional data interpretation (beyond the ACMG genes), with publications (i.e., materials and methods), and other activities as required for the program. 7- Provide secure backup of raw sequence data from the samples and all metadata associated with the project (i.e., sample tracking, storage, and QC information). The NWGC has worked successfully for more than 20 years with the NIH on a number of impactful, large-scale projects, and has a highly experienced team with a proven track record that is empowered by a robust administrative, computational, and instrumentation infrastructure that is state-of-the-art and can rapidly facilitate the goals of the All of Us Research Program. Depending on the needs of All of Us, the NWGC is flexible to handle the minimum number of samples proposed in all years while also being able to quickly scale to accommodate the maximum throughput needed by the All of Us Research Program (Table 1). The NWGC has extensive experience scaling in a short timeframe and has always met project goals and deadlines. The NWGC has a complete understanding of the requirements needed to be a full partner for the All of Us program and is fully capable and prepared.
