Technology Core

抽象--技术核心 U19提出了一种新的、完全集成的方法来了解疾病的进展和治疗 结核病(TB)的反应。我们将结合传统的方法来了解糖尿病的病理生理学 结核病，细菌遗传学和免疫学，系统生物学方法，包括基因组学，转录组学， 代谢组学、脂类组学、蛋白质组学和计算模型。我们将应用HTP“Omics”技术 以及对小鼠和分枝杆菌研究以及人类结核病现场研究的系统分析。数据 由HTP产生的和有针对性的最先进的方法将通过生物信息学和 建模方法，与领域专业知识相结合，将导致对 作为结核病感染进展和治疗反应的基础的分子网络，并预测 导致遏制或活动性疾病的复杂的生物行为；治疗、治愈或复发。 该计划将利用和增强多种创新的HTP技术。这些 技术已经在多个实验系统中建立，并将进行定制和进一步 为将其应用于本计划和适当的临床样本而开发。这些发展将 确保数据质量，最大限度地提高数据生成效率。所选择的方法是创新的 和最先进的，并将最大限度地提高我们的能力，以补充和扩展现有的全面 网络模型，并为作为原始OTB计划一部分生成的模型提供空间视角。我们 将广泛传播对现有技术和详细协议的修改和改进 使社区能够采用和进一步发展。

Abstract - Technology Core This U19 proposes a novel and fully integrated approach to understanding disease progression and treatment response in tuberculosis (TB). We will combine traditional approaches to understanding the pathophysiology of TB, bacterial genetics and immunology, with systems biology approaches including genomics, transcriptomics, metabolomics, lipidomics, proteomics, and computational modeling. We will apply HTP “Omics” technologies and systems analysis to murine and mycobacterial studies and to human field studies in tuberculosis. Data generated by HTP and targeted state-of-the-art approaches will be integrated through bioinformatic and modeling approaches, which, combined with domain expertise, will lead to a deep understanding of the molecular networks that underlie the progression of TB infection and response to treatment, and predict complex biological behaviors that lead to either containment or active disease; treatment cure or relapse. Multiple innovative HTP technologies will be leveraged and enhanced through this program. These technologies have been established in multiple experimental systems and will be customized and further developed for their application to this program and to clinical samples as appropriate. These developments will ensure data quality, and maximize the efficiency of data generation. The approaches chosen are innovative and state-of-the-art and will maximize our ability to complement and extend the existing comprehensive network models and provide spatial perspective for models generated as part of the original OTB program. We will disseminate modifications and improvements to extant technologies and detailed protocols broadly to enable adoption and further development by the community.