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Patient Genetic Determinants of Chronic Wound Microbiome Composition

慢性伤口微生物组成的患者遗传决定因素

基本信息

批准号：
10203567
负责人：
Caleb Dakotah Phillips
金额：
$ 42.14万
依托单位：
TEXAS TECH UNIVERSITY
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 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10203567
关键词：
Address Bacterial Model Biological Assay Categories Characteristics Chronic Clinical Communities Consequentialism Data Development Diabetes Mellitus Elderly Environment Epidemic Equation Foundations Genes Genetic Genetic Determinism Genetic Variation Genome Genomic Segment Genomics Genotype Goals Health Healthcare Systems Human Impaired healing Incidence Individual Individuality Infection Investigation Knowledge Lead Medical Care Costs Medicine Mental Depression Microbe Modeling Nature Obesity Outcome Patients Phenotype Physicians Population Predictive Value Predisposition Prevention Prevention therapy Public Health Quality of life RNA Research Research Design Risk Sampling Shapes Structure Testing Therapeutic Time United States Untranslated RNA Validation Variant Work Wound Infection Wound models base causal variant chronic wound cohort combat demographics design experimental study falls genetic variant genome wide association study genome-wide genomic locus healing host-microbe interactions improved individual variation information model insight mRNA Expression microbial microbial community microbiome microbiome alteration microbiome composition microorganism interaction model development mortality non-healing wounds pathogen predictive modeling predictive tools tool wound wound bed wound care

项目摘要

PROJECT SUMMARY Chronic wounds are an epidemic afflicting several million people in the United States, and many million more worldwide. The elderly, the obese and those with diabetes have much higher incidence of chronic wounds, and the proportion of the population that fall into these categories is rising. Chronic wounds are associated with considerable reductions in quality of life, including increased rates of depression and mortality, among others. The expansion of the chronic wound epidemic is also reflected in rapidly rising medical costs. The non- healing nature of these wounds is heavily influenced by microbial infection, and multiple bacterial species are commonly found to simultaneously occur in wounds as microbial communities. A recent study provided evidence that one's genetics shape the bacterial species that inhabit their chronic wounds and these species were consequential to healing rates. Recognizing the biomedical importance of understanding this relationship, the specific aims of the project are to: 1) Identify patient genomic loci associated with chronic wound microbiome characteristics; 2) Establish the feasibility of predictive modeling for chronic wound infections; and, 3) Functionally validate associated loci. The study design consists of comparing patients' chronic wound microbiomes to their genomes through a microbiome-genome wide association study. The design includes a discovery cohort of greater than 1,000 samples, regional imputation around lead SNPs and Bayesian fine-mapping to identify credible sets including likely causal variants. Based on results of association studies, specific genomic regions will be used to build the first predictive models for bacterial species occurrence in chronic wounds; it is anticipated that such models will eventually find application in predictive and therapeutic medicine. Model development will be accomplished by using the Bayesian credible sets of SNPs from associated regions to inform latent variables in a structural equation modeling framework. An independent validation cohort of greater than 250 samples will be used to assess the predictive power of these models. Also, wet lab functional validation experiments of SNPs most likely to be causal are expected to yield new mechanistic insights about host-microbe interactions consequential to chronic wounds. The long-term goal of this work is to leverage individual genetics to combat chronic wounds and improve public health outcomes.

项目总结