HIGH THROUGHPUT PROTEIN-PROTEIN INTERACTION INTERROGATION IN CANCER

埃默里功能基因组学分子相互作用中心(MicFG)，其在 高通量蛋白质-蛋白质相互作用研究技术(PPI) 发现化学铅和证实癌症的创新HTS测试开发记录 基因组学挖掘、数据库和数据集成能力，寻求成为 NCI癌症靶点发现和开发(CTDD)网络。人类基因组的改变 癌症基因组学倡议揭示的各种肿瘤类型，如癌症基因组 Atlas(TCGA)，通常导致蛋白质-蛋白质相互作用网络的重新布线，这反过来又推动 肿瘤的发生和发展。因此，确定PPI中的重要节点和网络 癌蛋白和肿瘤抑制因子被各种基因组数据集和 对它们在肿瘤发生和发展中的关键作用的验证有望揭示 全新的一类基于PPI的癌症靶点用于治疗开发。要做到这一点 目标，我们建议利用我们已建立的高通量PPI技术来询问 通过团队科学方法(I)快速确定致癌因素的癌症基因组学信息 基于TCGA和其他基因组数据集的选定癌症类型的PPI网络，(Ii)至 验证关键PPI节点或枢纽在肿瘤发生和发展中的功能作用，(Iii) 开发关键肿瘤相关PPI的HTS检测方法以丰富治疗靶点管道 以及(Iv)利用我们的信息学能力 用于优先PPI映射、功能性PPI验证和跨网络的基因组数据挖掘 数据共享和协作。我们的目标是弥合庞大的基因组数据集和 通过建立和询问癌症PPI靶点空间来发现治疗。带着我们的 PPI专业知识和最先进的高通量技术，高度适应 各种产出，我们打算作为一个积极的，协同的成员，在合作的运输 网络项目。

The Emory Molecular Interaction Center for Functional Genomics (MicFG), with its expertise in high throughput technologies for the study of protein-protein interactions (PPI) , productive track record of innovative HTS assay development for chemical lead discovery, and proven cancer genomics mining, database, and data integration capabilities, seeks to become a node in the NCI Cancer Target Discovery and Development (CTDD) Network. Genomic alterations in various tumor types, as revealed by cancer genomics initiatives such as The Cancer Genome Atlas (TCGA), often lead to re-wired protein-protein interaction networks, which in turn drive tumor initiation and progression. Thus, identifying prominent PPI nodes and networks among oncoproteins and tumor suppressors as enriched by various genomics datasets and the validation of their critical roles in tumorigenesis and progression are expected to reveal an entirely new class of PPI-based cancer targets for therapeutic development. To achieve this goal, we propose to utilize our established high throughput PPI technologies to interrogate cancer genomics information through a team science approach (i) to rapidly establish oncogenic PPI networks of selected cancer types based on TCGA and other genomic datasets, (ii) to validate functional roles of key PPI nodes or hubs in tumorigenesis and progression, (iii) to develop HTS assays for critical tumor-associated PPIs to enrich the therapeutic target pipeline of the NCI and the drug discovery field, and (iv) to leverage our informatics capability for genomics data mining for prioritized PPI mapping, functional PPI validation, and trans-network data sharing and collaboration. We aim to bridge the gap between vast genomic datasets and therapeutic discovery by establishing and interrogating the cancer PPI target space. With our PPI expertise and state-of-the-art high throughput technologies, which is highly adaptable to a variety of outputs, we intend to function as an active, synergistic member in collaborative trans- Network projects.