Sarcoidosis and A1AT Genomics & Informatics Center

描述（由申请人提供）： α-1 抗胰蛋白酶缺乏症 (A1 AT) 是一种常染色体隐性遗传病，与慢性阻塞性肺病 (COPD) 的不同风险相关，而结节病是一种全身性疾病，其特征是形成肉芽肿性病变，特别是在肺、肝、皮肤和淋巴结中，导致一系列显着异质性的临床表现，其病因和临床表现各不相同，但病程可变且不可预测。为了改善疾病分类，促进生物标志物发现并加速新疗法的出现，需要一种将临床研究结果与分子表型结果相结合的综合方法。结节病和 A1 AT 基因组学和信息学中心 (SAGIC) 将通过实现 NHLBI A1 AT 和结节病基因组研究 (GRADS) 计划的以下目标来促进这一进程：1) 协调临床中心活动，包括患者招募、表型分析和生物样本收集。 2) 对临床中心获得的样本进行转录组和微生物组分析，3) 数据分析和整合，4) 准备数据集以存放在 NHLBI BloLINCC 存储库中。这些目标将通过两个研究项目来实现。项目 1：A1 AT 微生物组 - 将解决以下假设：肺微生物组的变化决定 A1 AT 中肺部受累的程度，并且它们反映在替代组织中的 mRNA 和 microRNA 变化中；项目 2：结节病中的新分子表型 - 将解决以下假设：PBMC 中基因表达变化所反映的全身性炎症指示疾病程度、微生物组变化和肉芽肿分子网络。

DESCRIPTION (provided by applicant): Alpha-1 antitrypsin deficiency (A1 AT), an autosomal recessive genetic disease that is associated with a variable risk of COPD, and Sarcoidosis, a systemic disease characterized by the formation of granulomatous lesions especially In the lungs, liver, skin, and lymph nodes that leads to a dramatically heterogeneous set of clinical manifestations, differ in etiology and clinicl presentation but share a variable and unpredictable course. To improve disease classification, facilitate biomarker discovery and accelerate advent of novel therapy an integrative approach that combines the results of clinical studies with molecular phenotyping results is required. The Sarcoidosis and A1 AT Genomics and Informatics Center (SAGIC) will facilitate this process by addressing the following objectives for the NHLBI Genomic Research In A1 AT and Sarcoidosis (GRADS) program: 1) Coordination of Clinical Centers activities that include patient recruitment and phenotyping and biospecimen collection. 2) Performance of transcriptome and microbiome analyses of the samples obtained by the Clinical Centers, 3) Data analysis and integration, 4) Dataset preparation for deposit in the NHLBI BloLINCC repository. The objectives will be addressed through two research projects. Project 1: A1 AT microbiome - will address the hypothesis that shifts in the lung microbiome determine the extent of lung involvement In A1 AT and that they are reflected in mRNA and microRNA changes in surrogate tissues, and Project 2: Novel molecular phenotypes in Sarcoidosis - will address the hypothesis that systemic Inflammation as reflected in gene expression changes in PBMC Is indicative of disease extent, microbiome shifts and granuloma molecular networks.