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Tissue-specific functional genomics in the acute respiratory distress syndrome

急性呼吸窘迫综合征的组织特异性功能基因组学

基本信息

批准号：
10610722
负责人：
Vern Eric Kerchberger
金额：
$ 16.91万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10610722
关键词：
Academic Medical Centers Acute Acute Lung Injury Acute Respiratory Distress Syndrome Address Adult Advisory Committees Affect Biology Biopsy Cells Chronic Disease Clinical Cohort Studies Critical Care Critical Illness DNA Data Data Scientist Databases Diagnosis Disease Disease Outcome Disease susceptibility Doctor of Philosophy Electronic Health Record Electronic Medical Records and Genomics Network Enrollment Foundations Future Gene Expression Gene Expression Regulation Genes Genetic Genetic Predisposition to Disease Genetic Risk Genetic study Genotype Goals Healthcare Systems Heterogeneity Immune Individual Inflammation Investigation Knowledge Lead Lung Lymphocyte Measures Mentors Mentorship Methods Modeling National Heart, Lung, and Blood Institute Outcome Pathogenesis Patient-Focused Outcomes Patients Performance Phenotype Predisposition Qi Research Research Personnel Research Project Grants Resources Risk Sampling Single Nucleotide Polymorphism Source Strategic vision Structure Structure of parenchyma of lung Syndrome Testing Tissue Sample Tissue-Specific Gene Expression Tissues Training United States United States National Institutes of Health Variant Whole Blood biobank biomedical informatics career cell type classifier algorithm clinical translation cohort computer framework design differential expression disorder risk disorder subtype functional genomics gene function genetic analysis genetic information genetic variant genome wide association study high risk human tissue improved innovation mortality risk new therapeutic target novel patient oriented personalized care population based precision medicine prospective risk prediction skills transcriptome

项目摘要

PROJECT SUMMARY The acute respiratory distress syndrome (ARDS) affects more than 200,000 adults each year in the United States and carries a high mortality risk. Heterogeneity in susceptibility and outcomes are prominent features of ARDS, and improved understanding of the genetic underpinnings of ARDS would advance our ability to define ARDS subphenotypes, predict disease risk, and identify new therapeutic targets: a critical challenge identified in the NHLBI’s most recent Strategic Vision plan. This K01 proposal will provide Dr. V. Eric Kerchberger, MD with critical training for his long-term career goal of bringing precision medicine to critical care by applying his expertise in biomedical informatics and genetic analysis to leverage the power of large-scale electronic health record (EHR) databases and DNA biobanks. The project will be completed under the guidance of primary mentor Lorraine B. Ware, MD and co-mentor Wei-Qi Wei, MD, PhD, and a research advisory committee of experts in precision medicine, biomedical informatics, and functional genomics. By integrating existing GWAS- level genotyping with PrediXcan, an advanced functional genomics framework, this project will quantify tissue- specific gene expression levels for lung tissue and immune cells in 3,100 critically ill adults enrolled in the Validating Acute Lung Injury Markers for Diagnosis (VALID) Study cohort. Then, leveraging Dr. Kerchberger’s expertise in EHR phenotyping, we will validate the genetic findings from VALID in an independent sample of ARDS patients from BioVU, Vanderbilt University Medical Center’s large de-identified DNA biobank. This mentored research project has three specific aims: Aim 1: Test the association between genetic regulation of gene expression and ARDS susceptibility in at-risk adults. Aim 2: Test the association between genetic regulation of gene expression and patient-centered outcomes in ARDS. Aim 3: Use advanced phenotyping methods to identify ARDS patients and at-risk controls in BioVU, and replicate gene expression associations identified in VALID. Completion of these studies will yield novel methods to identify ARDS patients and at-risk controls from large EHR databases, and advance our understanding of tissue-specific gene expression in ARDS, bridging the gap between genetics and biology. The knowledge gained from this proposal will provide vital preliminary data for Dr. Kerchberger to design and execute future R01 proposals to study functional genomics in ARDS using NIH- supported EHR biobanks such as the Electronic Medical Records and Genomics Network and the NIH All of Us Project. Furthermore, Dr. Kerchberger will gain new skills in the clinical translation of functional genomics and advanced EHR phenotyping, forming the foundation for Dr. Kerchberger to independently lead collaborative teams of clinicians, geneticists, and data scientists to conduct large EHR-based studies of critical illness syndromes that will improve risk prediction, identify novel disease subtypes using genetic risk, and ultimately bring precision medicine to the critically ill patient.

项目总结

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Genome-wide association analyses of common infections in a large practice-based biobank.

DOI：
10.1186/s12864-022-08888-9
发表时间：
2022-09-27
期刊：
BMC GENOMICS
影响因子：
4.4
作者：
Jiang, Lan;Kerchberger, V. Eric;Shaffer, Christian;Dickson, Alyson L.;Ormseth, Michelle J.;Daniel, Laura L.;Leon, Barbara G. Carranza;Cox, Nancy J.;Chung, Cecilia P.;Wei, Wei-Qi;Stein, C. Michael;Feng, QiPing
通讯作者：
Feng, QiPing

Host Response to Infection: Not All Lymphopenia Is Created Equal in SARS-CoV-2.

宿主对感染的反应：SARS-CoV-2 中并非所有淋巴细胞减少症都是一样的。