Host-derived biomarker signatures to differentiate acute viral, bacterial, and fungal infection

宿主衍生的生物标志物特征可区分急性病毒、细菌和真菌感染

• 批准号: 9373089
• 负责人: Micah T. McClain
• 金额: $ 19.88万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-18 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9373089
• 关键词: Acute; Anti-Infective Agents; Bacteremia; Bacterial Infections; Biological Assay; Biological Markers; Blood specimen; Candida; Candidiasis; Clinic; Clinical; Critical Illness; Data; Development; Diagnosis; Diagnostic tests; Disease; Effector Cell; Enrollment; Etiology; Fever; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Generations; Goals; Hematologic Neoplasms; Immune; Immune response; Immunocompromised Host; Immunosuppression; Individual; Infection; Infection Control; Infectious Agent; Machine Learning; Methods; Microbiology; Modality; Mycoses; Organ Transplantation; Organism; Outcome; Pathogen detection; Patient risk; Patients; Resistance; Reverse Transcriptase Polymerase Chain Reaction; Risk; Sampling; Societies; Solid; Statistical Methods; Testing; Time; Viral; Virus Diseases; Work; accurate diagnosis; adjudicate; antimicrobial; base; candidemia; cohort; evaluation/testing; genomic signature; high dimensionality; high risk population; human subject; improved; improved outcome; individual patient; learning strategy; migration; novel; novel diagnostics; pathogen; peripheral blood; prototype; rapid diagnosis; therapy outcome; transcriptome sequencing

Statement of Work There is an urgent need for improved diagnostic tests for the evaluation of the etiology of febrile states, particularly in immunocompromised hosts. This project will develop host-based biomarker signatures capable of identifying the presence and pathogen class of infections in vulnerable immunocompromised human subjects, thus potentially allowing for earlier, more directed (and thus more effective) therapy as well as reducing the need for potentially harmful empiric anti-infective therapy. In this study we will a) perform high dimensional gene expression analysis on existing samples of at-risk hosts with proven candidemia, viral infection, bacterial infection, or noninfectious illness, b) develop peripheral blood-based gene expression signatures of candidemia and c) generate a combined multinomial classifier capable of differentiating four clinical states: viral infection, bacterial infection, fungal infection (candidemia) and noninfectious illness. The enclosed work offers a true paradigm shift in the way febrile illnesses in this high-risk population are diagnosed and managed.

工作说明书 迫切需要改进诊断试验来评估发烧的病因。 在各州，特别是在免疫受损的宿主中。该项目将开发基于主机的 能够识别感染的存在和病原体类别的生物标志物特征 脆弱的免疫受试者，因此可能允许更早、更多 定向(因此更有效)治疗，以及减少对潜在有害物质的需求 经验性抗感染疗法。在这项研究中，我们将a)进行高维基因表达 已证实为念珠菌血症、病毒感染、细菌感染的高危宿主样本的分析 感染或非传染性疾病，b)发展基于外周血液的基因表达 假丝酵母菌的签名和c)生成组合多项式分类器 区分四种临床状态：病毒感染、细菌感染、真菌感染(念珠菌血症) 和非传染性疾病。随附的作品提供了发烧方式的真正范式转变 对这一高危人群中的疾病进行诊断和管理。