Blood Transcriptional Biomarker Profiles for Category B Pathogens

描述(申请人提供)：生物武器以及自然发生的新发和重新出现的传染病是对美国人口安全的最大威胁之一。ABC优先病原体类别在美国的临床环境中很少遇到，因此应对此类威胁的准备水平仍然低得惊人，这一事实加剧了这一风险。因此，我们建议通过与世界上导致大量发病率和死亡率的地区的研究人员建立一个联盟来识别B类病原体的分子生物标记物签名。我们将寻求一种替代的和潜在的补充方法，通过开发基于宿主对感染的转录反应的评估的诊断标记来直接检测病原体。事实上，我们已经证明，在感染的急性期，血液基因表达谱会发生戏剧性的变化，而且这些变化是病原体特有的。在这个项目的背景下：(1)我们将收集具有良好特征的脓毒症患者的血液样本(伯克霍尔德氏菌/昆康大学，泰国)，持续发热(布鲁氏菌)。(2)我们将使用全基因组血液转录筛查(48,000个转录)确定由B类优先病原体引起的传染病的候选诊断特征和疾病严重程度的指标；(2)我们将使用全基因组血液转录筛查(48,000个转录)来确定B类优先病原体引起的传染病的候选诊断特征和疾病严重程度的指标；(3)我们将使用聚焦转录分析来验证候选的血液标志物。总而言之，该计划将支持一个富有成效的研究人员网络，其中包括研究临床医生、在免疫学和基因组学领域具有专业知识的研究科学家，以及由生物信息学家和生物统计学家组成的经验支持团队，他们将共同努力开发新的工具，以改进由B类优先病原体引起的感染患者的管理。

DESCRIPTION (provided by applicant): Biological weapons, as well as naturally occurring emerging and reemerging infectious diseases, are among the greatest threats to the safety of the US population. This risk is accentuated by the fact that the category ABC priority pathogens are rarely encountered in the US in clinical settings, and as a result the level of preparedness to respond to such threats remains alarmingly low. Therefore, we are proposing to identify molecular biomarker signatures for category B pathogens by creating a consortium with investigators working in areas of the world where they are causing substantial morbidity and mortality. We will pursue an alternative and potentially complementary approach to direct pathogen detection by developing diagnostic markers based on the assessment of the host transcriptional response to infection. Indeed, we have already demonstrated that dramatic changes in blood gene expression profiles occur during the acute phase of an infection, and that those changes are pathogen-specific. In the context of this project: (1) we will collect blood samples from well characterized patients with sepsis (Burkholderia pseudomallei / Khon Kaen University, Thailand), persistent fever (Brucella sp. / Centre d'lmmunologie de Marseille Luminy, France) and diarrheal diseases (Escherichia coli, pathogenic Vibrio strains, Shigella spp, Salmonella, Campylobacter jejuni and Caliciviruses / Department of Molecular Biomedicine, CINVESTAV& Microbiology Research Laboratory at Hospital General O'Horan of Merida, Mexico); (2) we will identify candidate diagnostic signatures and indicators of disease severity for infectious diseases caused by category B priority pathogens using a genome-wide blood transcriptional screen (48,000 transcripts); and (3) we will validate candidate blood markers using a focused transcriptional assay. In summary, this program will support a productive network of investigators, including research clinicians, research scientists with expertise in the immunology and genomics fields, as well as an experience support team of bioinformaticians and biostatisticians who will work together towards the development of novel tools that will improve the management of patients with infections caused by category B priority pathogens.