Multi-omic networks associated with COPD progression in TOPMed Cohorts

TOPMed 队列中与 COPD 进展相关的多组学网络

基本信息

批准号：
10592280
负责人：
RUSSELL Paul BOWLER
金额：
$ 75.09万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-05 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10592280
关键词：
African American African American population Biology Cause of Death Characteristics Chronic Obstructive Pulmonary Disease Complex Computers DNA Methylation Data Data Set Development Diagnosis Disease Progression Distal Environment Epidemiologist Epigenetic Process Ethnic Origin Genetic Genetic Markers Individual Investigation Jackson Heart Study Knowledge Lung Methods Minority Molecular Molecular Disease Molecular Profiling National Heart, Lung, and Blood Institute Not Hispanic or Latino Pathogenesis Pathway Analysis Pathway interactions Patients Phenotype Population Predisposition Proteins Proteomics Publications Pulmonary Emphysema Quantitative Trait Loci Race Repression Research Research Design Research Personnel Sample Size Scanning Scientist Smoker Spirometry System Technology Tobacco smoke Trans-Omics for Precision Medicine Transcript Underrepresented Minority Work X-Ray Computed Tomography airway obstruction alpha 1-Antitrypsin chronic airflow obstruction clinical phenotype cohort disease phenotype genetic variant genome sequencing improved metabolomics multidisciplinary multiple omics new therapeutic target novel novel diagnostics precision medicine prognostic single molecule soluble RAGE transcriptome sequencing transcriptomics unsupervised learning whole genome

项目摘要

PROJECT SUMMARY Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the US. Although COPD occurs predominantly in smokers, it is unknown why only a minority of smokers (~20-40%) develop chronic airflow limitation or destruction of distal airspaces (emphysema). The difference susceptibility to tobacco smoke could be explained by differences in genetics or environment, which lead to activation or repression of pathways that are important in the pathogenesis and progression of COPD. Recent advances in high throughput omics (whole genome sequencing, DNA methylation, RNA-Seq, proteomics and metabolomics) applied to NHLBI cohorts now permits a comprehensive assessment of the molecular profiles of susceptible patients. This proposal will use sparse multiple canonical correlation network analysis (SmCCNet) to integrate these existing -omics data from three NHLBI cohorts: COPDGene, Jackson Heart Study, and SPIROMICS. The three independent cohorts will allow replication of specific molecular networks which can be used to target new therapies or more precise prognostic information to individuals (i.e., precision medicine). The first two of these cohorts have large numbers of African American subjects, who are underrepresented in omics studies. We will perform population specific analyses, which will allow us to determine which molecular signatures and pathways might be specific to African Americans.

项目概要慢性阻塞性肺病（COPD）是美国第四大死因。虽然 COPD 主要发生在吸烟者身上，但尚不清楚为什么只有少数吸烟者 (~20-40%) 形成慢性气流受限或远端气腔破坏（肺气肿）。区别对烟草烟雾的易感性可以通过遗传或环境的差异来解释，这导致对发病机制和进展中重要的途径的激活或抑制慢性阻塞性肺病。高通量组学的最新进展（全基因组测序、DNA 甲基化、 RNA-Seq、蛋白质组学和代谢组学）应用于 NHLBI 队列现在可以进行全面的研究评估易感患者的分子谱。该提案将使用稀疏多重典型相关网络分析 (SmCCNet)，用于整合来自三个方面的现有组学数据 NHLBI 队列：COPDGene、Jackson Heart Study 和 SPIROMICS。三个独立的群体将允许复制特定的分子网络，可用于针对新疗法或更多疗法向个人提供精确的预后信息（即精准医学）。这些队列中的前两个拥有大量非裔美国人受试者，他们在组学研究中代表性不足。我们将进行特定人群的分析，这将使我们能够确定哪些分子特征和途径可能是非裔美国人特有的。