Successful Clinical Response In Pneumonia Therapy (SCRIPT) Systems Biology Center
肺炎治疗 (SCRIPT) 系统生物学中心成功的临床反应
基本信息
- 批准号:10582471
- 负责人:
- 金额:$ 12万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-01-17 至 2022-12-31
- 项目状态:已结题
- 来源:
- 关键词:AcinetobacterAddressAlveolarAlveolar MacrophagesAlveolusAnimal ModelAntibiotic TherapyAntiviral AgentsBacterial PneumoniaBacteriophagesBioinformaticsBiological MarkersBronchoalveolar LavageBronchoalveolar Lavage FluidCOVID-19Cause of DeathCell SeparationCellsCenters for Disease Control and Prevention (U.S.)CharacteristicsClinicalClinical DataClinical MedicineClinical MicrobiologyClinical TrialsCollectionCommunitiesComplexDNA VirusesDNA sequencingDataData SetDevelopmentDimensionsDiseaseEcosystemEducation and OutreachEquilibriumEtiologyFailureFungal DNAGenerationsGenesGeneticGoalsHumanImmune responseInfectionInfluenzaIntensive Care UnitsLeadLinkLiquid substanceLymphocyte SubsetLymphoid CellMachine LearningMechanical ventilationMedicalMetagenomicsMethylationModelingMultiomic DataMusMyeloid CellsNosocomial InfectionsNosocomial pneumoniaOutcomePathway interactionsPatientsPatternPneumoniaPopulationPreparationProspective cohortProtocols documentationPseudomonasPseudomonas aeruginosaPseudomonas aeruginosa infectionRNAReproducibilityResearchResearch PersonnelResearch Project GrantsRoleSamplingScienceSecondary toShotgunsSiteSorting - Cell MovementSpecimenStandardizationStreamStudy modelsSystemSystems BiologyTechnologyTestingTreatment FailureUnited States National Institutes of HealthValidationViralViral PneumoniaVirulenceanalytical toolbaseclinical carecohortdata managementdata pipelinedeep sequencingepigenomicsexperiencegenomic datagenomic profileshazardhumanized mouseimprovedinnovationmacrophagemicrobiomemicrobiome compositionmouse modelmultiple omicsneural networknew therapeutic targetnovelpathogenpathogen genomicspathogenic bacteriaphenomicsphenotypic datapneumonia modelpneumonia treatmentpredictive markerpredictive toolsprospectivepublic health relevancerepositoryresponsesuccesstooltranscriptome sequencingtranscriptomicstreatment responseviral DNAwhole genome
项目摘要
Modified Project Summary/Abstract Section
This innovative integrated systems biology application seeks to delineate the complex host/pathogen interactions occurring at the alveolar level that lead to unsuccessful response to therapy in serious pneumonia, including serious viral pneumonia. To achieve this objective, we will leverage our unique access to alveolar fluid collected as part of routine clinical care in mechanically ventilated patients with suspected pneumonia in our medical intensive care unit. Bronchoalveolar lavage fluid will be obtained serially from well characterized mechanically ventilated patients with serious viral or Pseudomonas or Acinetobacter bacterial pneumonias. Both of these CDC-designated serious hazard level bacterial pathogens have clinical failure rates as high as 50%. A robust clinical definition will allow comparison of both host and pathogen signatures associated with failure of therapy vs. success. These clinical specimens and extensive patient phenomics will anchor two mutually supportive and iterative research projects. Project One will deploy robust tools for flow sorting macrophage and lymphocyte subset populations, isolating RNA from these populations, and performing transcriptomic and epigenomic analysis to compare successful and unsuccessful host response. Project Two will focus on both specific pathogen genomic profiles associated with unsuccessful outcome and the differential microbiome response. Specific pathogen genomic profiles identified will be tested for causality in a unique humanized alveolar macrophage mouse model by the Technology Core. Changes in microbiome communities will be comprehensively assessed by shotgun deep sequencing to detect bacteriophage, other virus, and fungal DNA, in addition to bacterial. A Technical Core will perform cell sorting of BAL macrophage and lymphocyte subsets, RNA sequencing, and whole genome methylation, as well as perform the mouse pneumonia model studies. A Data Management and Bioinformatics Core will develop tools to reduce the dimensionality of these large comprehensive datasets, including the clinical phenomics, and provide them to the Modeling Core. The Modeling Core will then use an ecosystem-based approach to this complex adaptive system combined with unique machine learning tools and neural networks to generate biomarkers of host, pathogen and/or microbiome patterns predictive of successful pneumonia outcome. Predictive biomarkers developed in the Modeling Core will then be validated in a prospective confirmatory cohort of patients in whom analogous data will be generated. Biomarkers will also be tested for causality the mouse model. The Administrative Core will perform the outward- facing role of education and outreach to the community and sponsor, as well as regularly exchanging datasets, analytic tools, and specimens with NIH-sponsored/approved repository sites.
修改的项目摘要/摘要部分
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
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RICHARD G WUNDERINK其他文献
RICHARD G WUNDERINK的其他文献
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{{ truncateString('RICHARD G WUNDERINK', 18)}}的其他基金
Successful Clinical Response In Pneumonia Therapy (SCRIPT) Systems Biology Center
肺炎治疗 (SCRIPT) 系统生物学中心成功的临床反应
- 批准号:
10322470 - 财政年份:2021
- 资助金额:
$ 12万 - 项目类别:
Successful Clinical Response In Pneumonia Therapy (SCRIPT) Systems Biology Center
肺炎治疗 (SCRIPT) 系统生物学中心成功的临床反应
- 批准号:
10551461 - 财政年份:2018
- 资助金额:
$ 12万 - 项目类别:
Systems Biology Modeling of Severe Community-Acquired Pneumonia
严重社区获得性肺炎的系统生物学模型
- 批准号:
10551466 - 财政年份:2018
- 资助金额:
$ 12万 - 项目类别:
Successful Clinical Response In Pneumonia Therapy (SCRIPT) Systems Biology Center
肺炎治疗 (SCRIPT) 系统生物学中心成功的临床反应
- 批准号:
10326809 - 财政年份:2018
- 资助金额:
$ 12万 - 项目类别:
Project 1: Dynamic Host Responses During Resolution of HAP
项目 1:解决 HAP 期间的动态主机响应
- 批准号:
10097983 - 财政年份:2018
- 资助金额:
$ 12万 - 项目类别:
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