Project Summary: Funds are requested to purchase an Illumina NovaSeq 6000 Sequencing System to upgrade and expand sequencing capacity at the University of Texas Health at San Antonio (UTHSA). The new NovaSeq 6000 will be placed in and managed by the Genome Sequencing Facility (GSF) of Greehey Children’s Cancer Research Institute (GCCRI), a campus-wide shared core facility operated by a highly trained group of staff experienced with Illumina sequencing and genomic technologies and supported by well-qualified team of bioinformaticians. Since its inception in 2011, the GSF has greatly enhanced genomic research capability and fostered scientific collaborations within UTHSA and the greater San Antonio area, carrying out a wide range of sequencing protocols and applications. At the present time, high-throughput sequencing is conducted on a heavily utilized Illumina HiSeq 3000 sequencer that was installed in 2016, and there are no other publicly accessible high- throughput next-generation sequencing platforms within UTHSA or the surrounding San Antonio institutions. The heavy usage of the existing HiSeq 3000 has reached its capacity, and thus the GSF cannot meet the increasing demand for single cell analysis and cost-effective deep sequencing needs of UTHSA investigators and the broader research community. A range of basic, translational, clinical, and genomics studies at UTHSA depend on affordable, customizable high-throughput next-generation sequencing technologies. The requested instrumentation will allow GSF to continue to provide high-quality genomic data to support NIH-funded biomedical research, as shown by the 17 major users and 15 minor users whose research is described in this proposal. UTHSA has demonstrated a strong institutional commitment to the advancement of genomics research and fully supports this grant application by providing matching funds to contribute to continuing operation of the GSF. With the capacity of new requested Illumina NovaSeq 6000 System, a wide variety of research areas will be enhanced, including cancer, aging, pain control, diabetes, immunology, obesity, and neurodegenerative diseases. In addition to the proposed user group, the quality and affordability of high-throughput sequencing data enabled by the NovaSeq 6000 will allow investigators to develop new projects that may take their research into new directions. In addition, this instrumentation will strengthen our educational training programs for pre- and post-doctoral scientists, physicians, and scientists, and foster continued excellence in genomics and bioinformatics research at UTHSA. Thus, acquisition of an Illumina NovaSeq 6000 System will positively impact and expedite a large number of NIH-funded investigations, promote genomic scientific collaborations, and further accelerate translational research to improve the health of those in South Texas, a predominantly Hispanic population.