Sarcoidosis and A1AT Genomics & Informatics Center

描述(由申请人提供)： α-1抗胰蛋白酶缺乏症(A1AT)是一种常染色体隐性遗传病，与COPD的可变风险相关；结节病是一种全身性疾病，其特征是形成肉芽肿病变，尤其是在肺、肝脏、皮肤和淋巴结，导致一系列显著不同的临床表现，在病因和临床表现上不同，但有一个可变和不可预测的过程。为了改进疾病分类，促进生物标记物的发现，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基因组和信息学中心(SAGIC)将通过满足NHLBI A1 AT和结节病基因组研究(GRDS)计划的以下目标来促进这一进程：1)协调临床中心的活动，包括患者招募、表型和生物标本收集。2)临床中心获得的样本的转录组和微生物组分析的性能，3)数据分析和集成，4)准备存放在NHLBI BloLINCC储存库的数据集。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-将解决这样的假设，即肺微生物组的变化决定A1 AT中肺的受累程度，并反映在代理组织中的mRNA和microRNA变化中；项目2：结节病的新分子表型-将解决以下假设，即通过PBMC中基因表达变化反映的系统性炎症表明疾病程度、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.