Diagnosis of Infections in Humans with Microarrays

项目3：目前临床微生物学中使用的诊断方法的能力有限 在快速周转时间内识别病原体，以便迅速启动治疗干预和 适当的感染控制措施。这在面对新奇的新兴和 再次出现的病原体和潜在的生物制剂。而不是专注于确认数百人 在传统的基于微生物的方法中，我们提出了一种全面的 分析寄主对不同种类病原体的反应作为一种新的诊断工具。 根据我们对急性感染患者的初步研究，我们假设每个人 一类/组微生物诱导宿主反应模式[在免疫系统中]，该模式定义了 可用于诊断目的的特征性生物签名。利用微阵列进行基因表达 分析我们将确定：a)是否存在感染诱导的不同的特定生物特征 而不是由诸如自身免疫性疾病等其他非感染性条件和/或应激源引起的， 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原 微生物，以及c)生物特征是否可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革兰氏阴性细菌在 活体内的人血。目标2将确定人类血液中的基因表达是否允许区分 细菌感染和病毒感染之间的关系。目标3将确定已建立的生物签名是否允许 “不明原因感染”的诊断。目标4将确定血液中哪些免疫细胞携带微生物 生物签名。 这项研究将建立体内病原体生物签名的诊断和预后价值。我们的目标 是建立血液白细胞微阵列分析作为生物治疗诊断的平台技术 在治疗学和更大规模的公共卫生方面的接触和决策。

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.