PROJECT SUMMARY Next generation sequencing (NGS) technologies have revolutionized the world of genomics, transcriptomics and epigenomics. Core facilities play a critical role in academic institutions by providing access to the specialized expertise and instrumentation that are frequently out of reach to individual research laboratories. The Genomic and RNA Profiling (GARP) Core at Baylor College of Medicine (BCM) has over 12 years of experience in operating and administering next-generation sequencers and provides sequencing services for well over 100 investigators per year. The requested instrument, the Illumina NovaSeq X, is the latest Illumina next-generation sequencer that will replace our existing Illumina NovaSeq 6000 and enable the core to meet the rapidly changing and growing needs of investigators at BCM. The major advances of the NovaSeq X, important for our needs going forward, are greater output and flexibility, long-read sequencing applications, an integrated data analysis platform, a smaller data footprint and reduced sequencing costs. To assure an optimal infrastructure and maximum accessibility to BCM researchers, the Illumina NovaSeq X sequencer will be maintained and operated by the GARP Core. We anticipate that the new instrument will support all of our established Illumina library prep applications as well as allow for new applications and future growth. Most importantly, the NovaSeq X will enable the GARP Core to remain the sequencing hub for the majority of investigators, postdocs and students at BCM and extend support to surrounding Texas Medical Center institutions. The new instrument will enable us to continue highly customized research projects that require control over every step of our NGS operation starting with consultation and experimental design, sample processing, library construction, quality control and management, and delivery of sequencing data and applying high quality standards throughout the entire process. As the GARP Core develops additional epigenomics assays, the NovaSeq X will ensure capacity for new applications and ensure that we can offer them as one-stop workflows to the local research community. This new instrument will empower groups at BCM from a broad range of disciplines to understand the molecular mechanisms of human diseases. We have identified 19 participating groups with NIH funding engaged in both basic and clinical research that will benefit from the NovaSeq X sequencer. We believe the introduction of this new NGS instrument will have direct, broad, and immediate impact on many medically relevant fields.