NovaSeq X Plus Sequencing System - Project Summary / Abstract The University of Kansas Medical Center (KUMC) Genomics Core (GC) is requesting funds to upgrade high-throughput genomic sequencing capabilities with the purchase of an Illumina NovaSeq X Plus Sequencing System (NSXP). The GC has provided genomics services since 2002, initially using GeneChip microarrays, transitioning to Next Generation Sequencing (NGS) in 2011 with the HiSeq 2000/2500, and advancing to a NovaSeq 6000 (NS6K) in 2017. Demand for our NGS services has grown continuously, and we now serve a broad user base at the University of Kansas, affiliated Kansas Institutions, the Central Midwest region, and multiple states across the U.S. Recent advances in Illumina sequencing technology can reduce user cost, improve sequence-by-synthesis (SBS) chemistry, increase sequence throughput and data quality, improve onboard data analysis, and enhance file compression for more efficient data management. Unfortunately, our current instrument is unable to take advantage of these key advances, thereby disadvantaging our investigators with higher cost and lower sequencing quality. The proposed upgrade to the NSXP will ensure that GC sequencing capabilities are, and will remain, optimal for the foreseeable future. In addition to regional and national investigators representing 45 institutions across 27 states who have sought our services, the upgrade will have significant impact for our 20 major and 5 minor users with 45 NIH grants (28 R01-equivalent) identified in this application. Beyond aiding independent research programs, the enhanced attributes of the NSXP will advance the research missions of multiple NIH-funded centers including the NCI-designated Comprehensive University of Kansas Cancer Center (P30), the NIA–funded Alzheimer's Disease Research Center (P30); a NIDDK Center for Polycystic Kidney Disease translational research (U54); an NCATS CTSA (Frontiers: The Heartland Institute for Clinical and Translational Research (U54): and 3 Centers of Biomedical Research Excellence (COBRE) funded by NIH P20 Institutional Development Award (IDeA) grants. The NSXP will be located in space already optimized for Illumina NGS operations, which includes 10x Genomics Chromium X single cell and MissionBio Tapestri single cell DNA systems, 10x Visium spatial genomics, and a forthcoming Tecan DreamPrep NGS library automation robotics system. The NSXP will be integrated into a core network providing comprehensive administrative infrastructure including online request tracking, automated billing, and user-polling for quality assurance, in addition to bioinformatics support and technical support coupled to a newly expanded IT infrastructure. The GC is backed by a strong institutional commitment for both the acquisition and operation of the instrument. The acquisition of the NSXP will enhance rate and quality of discovery while reducing costs by approximately 59% per gigabase sequenced, thereby providing our large and diverse investigator clientele with improved data quality and savings that can be applied toward other health-related NIH-funded research.