PROJECT SUMMARY Genomic medicine has rapidly advanced in the past decade enabling earlier diagnosis and personalized treatment. However, only a few highly specialized centers in the US have the resources to take advantage of these advances in patient care. This has created a large health equity gap whereby patients cared for in typical community settings, often low-income and/or representing racial/ethnic minorities, do not receive equitable medical care. Another barrier to the wider utilization of genomic medicine is the poor dissemination of knowledge among clinicians, especially in community settings. A wide gap exists in the implementation of genomic medicine from diagnosis to personalized therapies, a field experiencing huge advances but still subject to wide disparities in accessibility. Our proposal aims to develop and test the implementation of a strategy to break down these barriers to genomic medicine, aligned with RFA-HG-20-036. Our target population is sick newborns. We propose a novel center, VIrtual GenOme CenteR (VIGOR), building upon our past and ongoing research as investigators for the NIH-funded Babyseq study (U19HD077671), Undiagnosed Disease Network (U01HG007690), and Center for Mendelian Genomics (UM1HG008900). VIGOR will be a center that can remotely support clinicians and families working in community NICUs. In AIM 1, we will establish the VIGOR center, and enroll and follow 250 eligible newborns and their families for 6 months within 4 community NICUs in the Northeast that serve diverse populations. In AIM 2, we will facilitate exome sequencing and create and return timely, comprehensive interpretive reports to families and physicians that: (1) relay diagnostic findings, (2) recommend clinical actions, (3) offer reanalysis of data for those with negative or inconclusive findings; and (4) provide additional research opportunities. In AIM 3, we will comprehensively assess implementation outcomes. Among neonatologists and within NICUs, we will examine 1) Appropriateness; 2) Feasibility; 3) Penetration; and 4) Equity (by race/ethnicity, insurance status, and primary language) and 5) Satisfaction of VIGOR use; among families, we will examine 1) Satisfaction; 2) Adverse mental health (stress and depression) and 3) Newborn clinical outcomes. This study will provide rigorous evaluation of implementing a virtual genome center into community clinical settings without highly specialized resources, thereby offering generalizable insights as to how best to implement genomic medicine at scale and for other age groups. Our intervention has great potential to address disparities in genomic medicine among low-income and URM populations and will enhance capacity for providers and health systems to utilize highly specialized genomic techniques in their communities.