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.

项目摘要慢性阻塞性肺疾病（COPD）是美国第四大死亡原因。虽然 COPD主要发生在吸烟者中，尚不清楚为什么只有少数吸烟者（〜20-40％）建立慢性气流限制或远端空域（肺气肿）的破坏。区别可以通过遗传学或环境的差异来解释对烟草烟雾的敏感性，导致激活或抑制在发病机理和进展中很重要的途径 COPD。高吞吐量法的最新进展（整个基因组测序，DNA甲基化， RNA-seq，蛋白质组学和代谢组学）现在允许全面评估易感患者的分子特征。该建议将使用稀疏的多个规范相关网络分析（SMCCNET）以整合三个现有的 - 摩体数据 NHLBI队列：Copdgene，Jackson Heart Study和Spiromics。三个独立人群将允许复制特定的分子网络，这些网络可用于针对新疗法或更多疗法给个人的精确预后信息（即精密医学）。这些队列的前两个在OMICS研究中，有大量的非裔美国人受试者代表人数不足。我们将执行特定人群的分析，这将使我们能够确定哪些分子特征和途径可能是针对非裔美国人的。