COBRE: Center for Computational Biology of Human Disease

项目总结 我们建议加强和扩大科布雷计算中心的研究能力 布朗大学及其附属医院的人类疾病生物学(CBHD)。高吞吐量数据来自 多种“组学水平”技术是识别和治疗人类疾病的基本因素。 这些数据的获取现在很简单，但对这些数据的高效和创造性的解释 仍然是初级教员在基本和翻译方面取得进步的严重障碍 生物医学科学。该中心的基本原则是实验室之间的密切合作 使用模型系统的科学家和使用计算和生物信息学工具的数据科学家 可以加速人类疾病研究的实施。在第一阶段，我们建立了CBHD Cobre 围绕计算生物学核心(CBC)以及对初级教员项目领导(9)和试点项目的支持 领导(8)。这些项目负责人已经获得了六架NIH R01，一架R35 Mira，一份NIH T32培训补助金， NIH R21，美国农业部拨款，斯隆奖和塞尔奖，总计约1790万美元。在第二阶段，我们将加强 这种研究环境支持四名新的项目负责人，并制定了一项增长和可持续发展计划 作为Cobre的分析和培训中心的CBC。我们创新的联合指导战略 其中每个项目负责人都由计算和生物或临床高级教员提供建议 已经被证明是成功的，这一点将得到延长。此外，我们将通过以下方式为CBC建立可持续的支持 扩大与Cobre毕业生和其他教职员工在外部赠款支持和内部资助方面的合作 员工数据科学家。该中心的长期目标是发展计算生物学基础设施的联系 对于大布朗和医院环境，这将使整个罗德岛受益。这样做的目的是 建议加强CBHD Cobre的基础设施，以确保初级教员项目的过渡 领导到R01资助的科学家，并提高更广泛的生物医学的计算熟练程度和多样性 研究社区。这三个目标是：目标1.支持初级教师项目领导追求的研究 人类疾病的生物学和计算方法。目标2.拓宽CBHD的研究环境 通过加强试点和辅导计划，增加教师招聘和促进资金投入 项目负责人的独立性。目标3.通过增加人员编制来加强计算生物学核心 并在布朗生物医学社区内提供更广泛的机会，以建立可持续性。四项新研究 项目是：1.生殖粘膜中T细胞分化和功能的局部调节；2：图谱 体外循环肿瘤细胞的基因表达和机制表型3：长程变构作图 CRISPR-Cas9中的通路；4：模拟远程调控相互作用以预测基因表达 图卷积网络。

PROJECT SUMMARY We propose to strengthen and extend the research capacity of the COBRE Center for the Computational Biology of Human Disease (CBHD) at Brown University and affiliated hospitals. High throughput data from multiple ‘omics-level’ technologies are fundamental factors in the identification and treatment of human disease. The acquisition of these data is now straightforward, but the efficient and creative interpretation of these data remain a serious impediment to progress for junior faculty in both the basic and translational aspects of biomedical science. The underlying principle of this Center is that close collaboration between laboratory scientists working with model systems and data scientists working with computational and bioinformatics tools can accelerate the implementation of human disease research. In Phase 1, we established the CBHD COBRE around a Computational Biology Core (CBC) and support for junior faculty Project Leaders (9) and Pilots Project leaders (8). These Project Leaders have been awarded six NIH R01s, an R35 MIRA, an NIH T32 Training Grant, an NIH R21, a USDA grant, a Sloan Award, and a Searle Award, totaling ~$17.9M. In Phase 2 we will strengthen this research environment with support for four new Project Leaders and a plan for growth and sustainability of the CBC that serves as the analysis and training hub of this COBRE. Our innovative joint mentoring strategy where each Project Leader is advised by both computational and biological or clinical senior faculty members has proven successful, and this will be extended. Moreover, we will build sustainable support for the CBC through expanded collaboration with COBRE graduates and other faculty on external grant support plus internally funded staff data scientists. The long-term goal of the Center is to grow a nexus of computational biology infrastructure for the greater Brown and hospital environments that will benefit all of Rhode Island. The objective of this proposal is to strengthen the infrastructure of the CBHD COBRE to ensure the transition of junior faculty Project Leaders to R01-funded scientists, and raise the computational proficiency and diversity of the broader biomedical research community. The three Aims are: Aim 1. Support the research of junior faculty Project Leaders pursuing biological and computational approaches to human disease. Aim 2. Broaden the CBHD research environment through enhanced Pilot and Mentoring programs that increase faculty recruitment and promote funding independence for Project Leaders. Aim 3. Strengthen the Computational Biology Core through enhanced staffing and broader access across the Brown biomedical community to build sustainability. The four new Research Projects are: 1. Local Regulation of T-cell Differentiation and Function in the Reproductive Mucosa; 2: Profiling Gene Expression and Mechanophenotype in Circulating Tumor Cells Ex Vivo; 3: Mapping Long-range Allosteric Pathways in CRISPR-Cas9; 4: Modeling Long-range Regulatory Interactions to Predict Gene Expression Using Graph Convolutional Networks.