PROJECT SUMMARY The long term goal of the COBRE for Computational Biology of Human Disease (CBHD) is to enhance the integration of basic biological and computational approaches to the study of human disease at Brown, its affiliated hospitals and across Rhode Island. Realizing this goal requires expertise that can support researchers across the spectrum from molecular biologists and clinical researchers using high throughput sequencing, to data scientists mining large publicly available human genomic datasets. In the initial Phase 1 support for this COBRE, we established the CBHD community and built the Computational Biology Core (CBC) facility to support junior faculty Project Leaders (PLs) that spanned this range of research. This support has led to seven NIH R01/R35 awards plus additional grants for our Project Leaders and Pilot awardees totaling more than $17.9M. In this Phase 2 renewal proposal we will strengthen and broaden the support for the CBC to enable a new cohort of CBHD COBRE PLs, plus other researchers in the Brown biomedical community, to advance their research into the computational biology of human disease. Computational and bioinformatic analyses have become a common language in contemporary biomedical research and are central tools required for researchers to realize the advances in genome enabled science. Our CBHD COBRE seeks to translate these tools into shared, accessible resources that will strengthen the competitiveness, and sense of community for all biomedical researchers in Rhode Island. The proximate goal of this COBRE in Phase 2 will be providing support for junior faculty PLs and Pilot awardees in the analysis and interpretation of massive sequencing datasets generated in their own labs or obtained from publicly available datbases. This will provide support for investigators who lack resources to build the necessary skill sets within their research groups, and accelerate their progress towards research funding independence. The central approach of the CBC will be to serve as a hub of collaborative service through the development of reproducible software pipelines and providing workshops for training of researchers to acquire bioinformatics fluency. This will enhance scientific interactions between diverse projects and broaden the sense of the community across the CBHD COBRE. The long-term goal of the CBC is to provide a sustainable resource to support the analytical challenges in ‘omics-scale human disease research across Brown University, our affiliated hospitals, and other researchers in Rhode Island. This will be achieved through three Specific Aims: 1. Strengthen computational and bioinformatics support for biomedical researchers; 2. Develop reproducible pipelines and interfaces to global data analysis and data sharing platforms; 3. Extend training and workshops to enhance computational skills of the broader community. This will bring the language of computational biology to a broader audience and increase the skill levels across the community, enhancing research capacity for all.