Diagnosis of Infections in Humans with Microarrays

用微阵列诊断人类感染

• 批准号: 7686544
• 负责人: Octavio Ramilo
• 金额: $ 26.25万
• 依托单位: BAYLOR RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7686544
• 关键词: Acute; Adjuvant Chemotherapy; Autoimmune Diseases; Biological Assay; Blinded; Blood; Blood Cells; Categories; Cells; Characteristics; Class; Clinical; Clinical Microbiology; Clinical Research; Condition; Culture Techniques; Data; Databases; Decision Making; Detection; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Disease Marker; Dose; Escherichia coli; Evaluation; Gene Expression; Gene Expression Microarray Analysis; Genes; Goals; Gram-Negative Bacteria; Granulopoiesis; Human; Immune; Immune response; Immune system; In Vitro; Individual; Infection; Infection Control; Influenza; Interferon-alpha; Leukocytes; Malignant Neoplasms; Measures; Messenger RNA; Microarray Analysis; Microbe; Molecular Biology; Molecular Diagnosis; Netherlands; Pathogenesis; Patients; Pattern; Public Health; Purpose; Role; Series; Severity of illness; Staphylococcus aureus; Steroids; Systemic Lupus Erythematosus; Techniques; Technology; Testing; Therapeutic; Therapeutic Intervention; Time; Transplantation; Trauma; Viral; Virus; Virus Diseases; base; biothreat; cohort; cytokine; in vivo; interdisciplinary approach; malignant breast neoplasm; microbial; microorganism; novel; novel diagnostics; pathogen; prognostic; stressor; tool

Project 3: The diagnostic methods currently used in clinical microbiology have limited capabilities to identify pathogens in a rapid turn-around time that allows prompt initiation of a therapeutic intervention and appropriate infection control measures. This is especially relevant when facing novel emerging and reemerging pathogens and potential biothreat agents. Rather than focusing on the identification of hundreds of potentially pathogenic agents in a traditional microbe-based approach, we propose a comprehensive analysis of the host response to different classes of pathogens as a novel diagnostic tool. Based on our preliminary studies in individuals with acute infections, we hypothesize that each class/group of microorganisms induces a host response pattern [in the immune system] which defines a characteristic biosignature that can be used for diagnostic purposes. Using microarray gene expression analysis we will determine: a) whether there are infection-induced specific biosignatures which are different than those induced by other non-infectious conditions and/or stressors such as autoimmune diseases, cancer, trauma, and transplantation; b) whether this biosignature can identify different classes of pathogenic microorganisms, and c) whether the biosignature can be used as a prognostic indicator of disease severity in different types of infections. Aim 1 will determine whether Gram positive and GRam negative bacteria yield different biosignatures in human blood in vivo. Aim 2 will determine whether gene expression in human blood will permit to distinguish between bacterial and viral infections. Aim 3 will determine whether established biosignatures permit diagnosis of "unknown infection". Aim 4 will determine which immune cells in blood carry the microbe biosignature. This study will establish the diagnostic and prognostic value of pathogen biosignatures in vivo. Our goal is to establish microarray analysis of blood leukocytes as a platform technology for the diagnosis of biothreat exposure and decision making with regard to therapeutics and, on a larger scale, Public Health.

项目3：目前用于临床微生物学的诊断方法能力有限， 在允许迅速启动治疗干预的快速周转时间内识别病原体， 采取适当的感染控制措施。这一点在面对新出现的、 重新出现的病原体和潜在的生物威胁剂。而不是专注于识别数百个 在传统的基于微生物的方法中，我们提出了一个全面的 分析宿主对不同种类病原体的反应，作为一种新的诊断工具。 基于我们对急性感染个体的初步研究，我们假设， 一类/一组微生物诱导宿主反应模式[在免疫系统中]，其定义了 特征性生物签名，可用于诊断目的。使用微阵列基因表达 分析我们将确定：a）是否存在不同的感染诱导的特异性生物特征 而不是由其他非感染性条件和/或应激源如自身免疫性疾病诱导的那些， 癌症、创伤和移植; B）这种生物特征是否可以识别不同类别的致病性肿瘤， 微生物，和c）生物标记是否可以用作疾病严重程度的预后指标， 不同类型的感染。 目标1将确定革兰氏阳性和GRAM阴性细菌是否产生不同的生物特征， 人体血液目的2将确定人类血液中的基因表达是否允许区分 细菌和病毒感染之间的联系目标3将确定已建立的生物特征是否允许 诊断为“不明感染”。目标4将确定血液中哪些免疫细胞携带微生物 生物特征 本研究将建立病原体生物特征在体内的诊断和预后价值。我们的目标 是建立血液白细胞的微阵列分析作为诊断生物威胁的平台技术， 接触和决策方面的治疗，并在更大范围内，公共卫生。