Metagenomic profiling of urinary cell-free DNA to monitor urinary tract infection after kidney transplantation
尿液游离 DNA 宏基因组分析用于监测肾移植后尿路感染
基本信息
- 批准号:10576328
- 负责人:
- 金额:$ 70.1万
- 依托单位:
- 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:2020-03-10 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:16S ribosomal RNA sequencingAcuteAddressAffectAlgorithmsAntibiotic ResistanceAntibiotic susceptibilityAntibioticsBacteriaBiochemicalBioinformaticsBiological AssayCessation of lifeClinicalClinical MarkersCommunicable DiseasesCost SavingsDNADNA sequencingDataDevelopmentDiagnosisDiagnostic testsDrug resistanceEvaluationGeneral PopulationGoalsHealth BenefitHealth Care CostsImmune responseInfectionInjuryInvestigationKidney TransplantationLifeMapsMeasurementMedicalMetagenomicsMethodologyMethylationMonitorPatient MonitoringPatient-Focused OutcomesPatientsPerformancePersonsPilot ProjectsProspective cohortProspective, cohort studyQuestionnairesResearchResearch DesignResistanceResolutionSamplingSeverity of illnessSortingSpecimenTechnologyTestingTimeTranslatingTransplant RecipientsTransplantationUrinary MicrobiomeUrinary tract infectionUrineViralVisitWorkantibiotic resistant infectionscell free DNAco-infectioncohortcommensal microbescostdesigndiagnosis standardepigenetic markerepigenetic profilingexperiencegenetic approachgraft functionimprovedmetagenomemetagenomic sequencingmicrobiomenanoporenovelnovel strategiespathogenpoint of care testingpost-transplantprecision medicineprogramsresponse to injurysample collectionsingle moleculetissue injurytooltransplant centersurinary
项目摘要
PROJECT SUMMARY
More than 15,000 patients receive life-saving kidney transplants in the US every year. Nevertheless, frequent
post-transplant complications limit the outlook for kidney transplant recipients. Urinary tract infections (UTIs),
including multi-drug antibiotic-resistant infections, occur at an alarmingly high rate after kidney transplantation.
At least 20% of kidney transplant recipients experience a serious UTI in the first 3 months after transplantation.
UTI has been associated with development of urosepsis, decreasing graft function, graft loss, and death.
The current gold standard for diagnosis of UTI is bacterial culture, which is fundamentally limited by its ability to
detect only culturable bacteria. Furthermore, bacterial culture does not inform about co-infections, commensal
microbiota, or the host response to infection. New biochemical and genetic approaches developed by our groups
can fundamentally change the paradigm for UTI diagnosis and transplant monitoring.
The goal of this proposal is to develop and apply precision medicine approaches for the monitoring of UTIs after
kidney transplantation. We will utilize (1) newly developed technologies for the metagenomic sequencing of
ultrashort fragments of cfDNA in urine, (2) new metagenomic host-response measurements, (3) technologies to
perform bioinformatic sorting of resistance determinants, and (4) new approaches to perform rapid cfDNA
metagenomic sequencing and direct profiling of epigenetic markers comprised within cfDNA based on Oxford
Nanopore Technologies.
In the first Aim, we will investigate the utility of metagenomic sequencing of urinary cfDNA as a tool to monitor
UTIs and to profile the urinary microbiome. This concept is supported by extensive pilot data. In the second Aim
we will investigate a cfDNA metagenomic sequencing assay that informs the degree of host injury due to
infection. This second Aim is also supported by significant results from pilot data. In the third Aim, we will
investigate the performance of novel, Nanopore sequencing technologies and algorithms that will enable a lower
cost, faster turnaround time, and greater utility of cfDNA metagenomic sequencing assays.
Together, these assays will provide new avenues to monitor infections of the urinary tract, profile antibiotic
resistance, describe the urinary microbiome, and examine host-pathogen interactions.
More than 15,000 patients receive kidney transplants each year, and many of these patients suffer complications
from UTI. In the general population, UTI is one of the most common medical problems, with 150 million persons
affected per year worldwide. Successful implementation of these studies will provide new avenues for the
monitoring of bacterial UTI and will thereby address an acute medical need in kidney transplantation, and by
extension, a substantial health benefit to the general public.
项目总结
项目成果
期刊论文数量(0)
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Darshana Dadhania其他文献
Darshana Dadhania的其他文献
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{{ truncateString('Darshana Dadhania', 18)}}的其他基金
Metagenomic profiling of urinary cell-free DNA to monitor urinary tract infection after kidney transplantation
尿液游离 DNA 宏基因组分析用于监测肾移植后尿路感染
- 批准号:
10361456 - 财政年份:2020
- 资助金额:
$ 70.1万 - 项目类别:
North East Consortium for Transplant outcomes in APOL1 kidney Recipients (NECTAR) Clinical Center
APOL1 肾移植结果东北联盟 (NECTAR) 临床中心
- 批准号:
9980194 - 财政年份:2017
- 资助金额:
$ 70.1万 - 项目类别:
North East Consortium for Transplant outcomes in APOL1 kidney Recipients (NECTAR) Clinical Center
APOL1 肾移植结果东北联盟 (NECTAR) 临床中心
- 批准号:
9441460 - 财政年份:2017
- 资助金额:
$ 70.1万 - 项目类别:
RENAL TRANSPLANTATION IN CROSSMATCH POSITIVE RECIPIENTS
交叉匹配阳性受者的肾移植
- 批准号:
7604190 - 财政年份:2007
- 资助金额:
$ 70.1万 - 项目类别:
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