Core C: Genomics and Bioinformatics

项目总结 基因组学和生物信息学核心(核心C)将提供最先进的测序技术，以实现 建议的免疫基因组和表观基因组测量以及相应的生物信息学分析 P01计划项目。这一核心将部署广泛的批量和单细胞下一代测序 为项目中的临床前和临床生物检疫优化的技术。支持的技术 这一核心包括：用于新抗原预测的整个外显子组测序，用于预测新抗原的批量和单细胞RNA测序 分子和细胞网络的推断，批量和单细胞T细胞受体测序查询T细胞 克隆及其相关功能，以及用于查询表观遗传和转基因的ATAC-SEQ和CHIP-SEQ技术 教条式的规定。这些技术与优化的生物信息学管道和组件相辅相成。 核心和计划研究人员为免疫基因组学量身定做的计算方法。生物信息学 方法针对计划项目和蛋白质组学中生成的数据集的定制分析而量身定做 来自数字病理和质量细胞术核心(核心D)的测量，以支持TME表征。 这一基因组学和生物信息学核心将对THERA-R的生物谱系进行进一步的综合分析。 在本计划的项目中采用最佳方案，并促进计划的协同作用。计算性的 此核心中使用的方法将汇总高维数据以提供低维汇总 生物统计学和临床试验核心(核心B)，以确定免疫的分子和细胞决定因素 治疗反应和抵抗力，以支持项目确定新的治疗策略以实现精确度 免疫疗法。 核心联合领导人结合了基因组技术(Yegnasubramanian博士)和生物信息学方面的专业知识 (费尔蒂希博士)。除了特定于计划的目标外，此核心还进一步利用 NCI指定的约翰·霍普金斯大学SCCC核心赠款支持的实验和计算 基因组学核心(ECGC；联席主任Yegnasubramanian；联合调查员Fertig)。两位领导人，费尔蒂希和 Yegnasubramanian与一家公司合作，在基因组学和生物信息学方面拥有既定的记录 另一种和计划调查员非常适合启用建议的分析和生物信息学分析 这个核心中的程序。

PROJECT SUMMARY The Genomics and Bioinformatics Core (Core C) will provide state-of-the-art sequencing technologies to enable immunogenomic and epigenomic measurements and corresponding bioinformatics analyses for the proposed P01 Program Projects. This Core will deploy a wide range of bulk and single cell next generation sequencing technologies optimized for the preclinical and clinical biospecimens in the Projects. Technologies supported by this Core include: whole exome sequencing for neoantigen prediction, bulk and single cell RNA-sequencing for inference of molecular and cellular networks, bulk and single cell T cell receptor sequencing to query T cell clones and their associated function, and ATAC-seq and ChIP-seq technologies to query epigenetic and tran- scriptional regulation. These technologies are complemented by optimized bioinformatics pipelines and compu- tational methods tailored to immunogenomics developed by the Core and Program Investigators. Bioinformatics methods are tailored to customized analyses of the datasets generated in Program Projects, and proteomics measurements from the Digital Pathology and Mass Cytometry Core (Core D) to support TME characterization. This Genomics and Bioinformatics Core will perform further integrative analyses of biospecimens of the thera- peutic regimens employed across Projects in this Program and promote Program Synergy. The computational methods employed in this Core will summarize the high-dimensional data to provide low dimensional summaries to the Biostatistics and Clinical Trials Core (Core B) to identify molecular and cellular determinants of immuno- therapy response and resistance to support the Projects in defining new therapeutic strategies for precision immunotherapy. The Core Co-Leaders combine expertise in genomics technologies (Dr. Yegnasubramanian) and bioinformatics (Dr. Fertig). In addition to the Program-specific goals, this Core further leverages the existing infrastructure in the NCI-designated Johns Hopkins University SCCC Core Grant-supported Experimental and Computational Genomics Core (ECGC; Co-Director Yegnasubramanian; Co-Investigator Fertig). Both Leaders, Fertig and Yegnasubramanian, have an established track record in Genomics and Bioinformatics in collaboration with one another and Program Investigators ideally suited to enable the profiling and bioinformatics analysis proposed for the Program in this Core.