Lung Genomics Research Consortium

肺基因组学研究联盟

基本信息

批准号：
7939886
负责人：
MARK W GERACI
金额：
$ 375.97万
依托单位：
NATIONAL JEWISH HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7939886
关键词：
Accounting Address Affect Bioinformatics Biological Blood Categories Cause of Death Characteristics Chest Chronic Chronic Obstructive Airway Disease Chronic lung disease Classification Clinical Clinical Data Clinical Investigator Communities Complement Complex DNA DNA Methylation DNA Sequence Data Data Set Databases Death Rate Descriptor Development Diagnosis Diagnostic Diagnostic radiologic examination Dimensions Disease Enrollment Environmental Exposure Epigenetic Process Etiology Evolution Feedback Fibrosis Gene Expression Profile Genetic Genomics Genotype Goals Hamman-Rich syndrome Heterogeneity Histologic Histology Human Image Image Analysis Incidence Individual Inflammatory Intervention Investments Lead Lung Lung diseases Measures Medicine Messenger RNA Molecular Molecular Bank Molecular Genetics Molecular Profiling National Heart, Lung, and Blood Institute Online Systems Operative Surgical Procedures Outcome Pathogenesis Pathologic Pathologist Pathology Pathway interactions Pattern Phenotype Physiology Population Populations at Risk Prevalence Process Public Health Pulmonary Emphysema Pulmonary Fibrosis RNA RNA Sequences Recording of previous events Research Research Personnel Risk Serological Severities Specimen Staging Structure of parenchyma of lung Surveys System Testing Therapeutic Tissues Training Programs United States Validation base biobank clinical phenotype data portal design empowered falls genome-wide improved interest lung imaging meetings molecular phenotype multidisciplinary novel peripheral blood programs prospective public health relevance radiologist tool

项目摘要

DESCRIPTION (provided by applicant): Chronic lung diseases represent a broad spectrum of chronic fibrosing/inflammatory lung conditions that are for the most part poorly responsive to treatment and often fatal. COPD/emphysema is the fourth leading cause of death in the United States and the incidence and rate of death from pulmonary fibrosis is increasing each year. Although progress has been made in interpretation of the clinical, radiological, and pathological features of chronic lung disorders, and progress in determining the pathobiology continues, the causes, biologic mechanisms, and therapeutic options remain obscure. Moreover, predicting individuals or populations at risk for developing any of these complex diseases, at present, is not possible. To address this challenge, we plan to create a genetic, molecular, and quantitative clinical phenotyping data warehouse with bioinformatic tools that will empower investigators to make fundamental discoveries in disease pathogenesis, refine diagnostic criteria, and lead to real gains in personalized medicine. The composite genetic, genomic, and epigenetic signature combined with quantitative clinical phenotypes has the potential to characterize the dynamic biological state of a complex disease and complement existing diagnostic approaches that are reliant on traditional clinical measures of disease. In the proposed project, we plan to extend the scope and impact of the NHLBI Lung Tissue Research Consortium (LTRC) biorepository by creating the Lung Genomics Research Consortium (LGRC), a comprehensive genetic, molecular, and quantitative clinical phenotyping warehouse. Our overall hypothesis is that a genetic, molecular, and quantitative clinical phenotyping warehouse combined with a rich clinical database will enable the lung research community to make fundamental discoveries in disease pathogenesis, refine diagnostic criteria, and lead to real gains in personalized medicine. We plan to pursue this hypothesis through the following aims. Specific Aim 1: Establish a genetic, genomic, and epigenetic molecular library to complement the existing clinical database in the LTRC. Specific Aim 2: Develop a quantitative clinical phenotyping platform using existing LTRC data, as well as an enhanced data set including novel quantitative CT and histology imaging analyses. Specific Aim 3: Establish a publicly-accessible database that would integrate the genetic, molecular, and quantitative phenotyping data with the existing clinical data in the LTRC and provide query and data exploration tools that are easily accessible to the lung research community. These discoveries will enable clinicians to: 1) identify individuals at risk of developing chronic lung diseases; 2) diagnose these conditions earlier; 3) identify novel mechanisms that cause these diseases; 4) reclassify disease entities into categories more representative of molecular and cellular pathogenic mechanisms regardless of traditional disease categories; and 5) develop personalized approaches to treatment. PUBLIC HEALTH RELEVANCE: Chronic lung diseases affect a significant portion of the population, the incidence of COPD/emphysema and idiopathic interstitial pneumonia are increasing annually, and COPD is the fourth leading cause of death in the U.S. (www.cdc.gov). Despite major investments that have been made in lung research over the past two decades, these disease remains major public health problems that paradoxically are increasing in prevalence, incidence, and severity. To address this challenge, we plan to create a genetic, molecular, and quantitative phenotyping data warehouse with bioinformatic tools that will empower investigators to make fundamental discoveries in disease pathogenesis, refine diagnostic criteria, and lead to real gains in personalized medicine. These discoveries will enable clinicians to: 1) identify individuals at risk of developing chronic lung diseases; 2) diagnose these conditions at an earlier stage; 3) identify novel mechanisms that cause chronic lung disease; and 4) eventually develop personalized therapeutic strategies for intervention.

描述（由申请人提供）：慢性肺部疾病代表了一系列慢性纤维纤维/炎性肺部疾病，这些疾病大多数情况下对治疗的反应不佳，而且通常是致命的。 COPD/肺气肿是美国第四大死亡原因，肺纤维化的发病率和死亡率每年都在增加。尽管在解释慢性肺部疾病的临床，放射学和病理学特征方面已经取得了进展，并且在确定病理生物学继续进行的进展中，原因，原因，生物学机制和治疗方案仍然晦涩难懂。此外，目前不可能预测患有任何这些复杂疾病的个人或人群。为了应对这一挑战，我们计划使用生物信息学工具创建一个遗传，分子和定量的临床表型数据仓库，这些工具将使研究人员能够在疾病发病机理，完善诊断标准中产生基本发现，并在个性化医学中获得真正的收益。复合遗传，基因组和表观遗传学特征与定量临床表型相结合具有表征复杂疾病的动态生物学状态，并补充依赖传统疾病临床测量的现有诊断方法。在拟议的项目中，我们计划扩大NHLBI肺组织研究联盟（LTRC）生物座的范围和影响，通过创建肺基因组研究联盟（LGRC），这是一种综合的遗传，分子和定量的临床表型仓库。我们的总体假设是，结合丰富的临床数据库的遗传，分子和定量临床表型仓库将使肺部研究界能够在疾病发病机理，改进诊断标准中产生基本发现，并在个性化医学中获得真正的收益。我们计划通过以下目的提出这一假设。具体目标1：建立一个遗传，基因组和表观遗传学分子文库，以补充LTRC中现有的临床数据库。具体目标2：使用现有的LTRC数据以及增强的数据集，包括新的定量CT和组织学成像分析，开发一个定量临床表型平台。特定目的3：建立一个可公开访问的数据库，该数据库将将遗传，分子和定量表型数据与LTRC中的现有临床数据整合在一起，并提供肺部研究社区易于访问的查询和数据探索工具。这些发现将使临床医生能够：1）确定有患慢性肺部疾病的风险的人； 2）较早诊断这些情况； 3）确定引起这些疾病的新型机制； 4）将疾病实体重新分类为类别，无论传统疾病类别如何，都会更代表分子和细胞致病机制； 5）开发个性化的治疗方法。公共卫生相关性：慢性肺部疾病会影响大部分人口，COPD/肺气肿的发生率和特发性间质性肺炎每年增加，COPD是美国的第四个主要死亡原因（www.cdc.gov）。尽管过去二十年来对肺部研究进行了重大投资，但这些疾病仍然是主要的公共卫生问题，这些问题矛盾的是，患病率，发病率和严重程度正在增加。为了应对这一挑战，我们计划使用生物信息学工具来创建遗传，分子和定量的表型数据仓库，这些工具将使研究人员能够在疾病发病机理，完善诊断标准中产生基本发现，并在个性化医学中取得真正的增长。这些发现将使临床医生能够：1）确定有患慢性肺部疾病的风险的人； 2）在较早的阶段诊断这些情况； 3）确定引起慢性肺部疾病的新型机制； 4）最终制定了个性化的治疗策略进行干预。