Blood Transcriptional Biomarker Profiles for Category B Pathogens

B 类病原体的血液转录生物标志物谱

• 批准号: 8208890
• 负责人: Damien Chaussabel
• 金额: $ 118.36万
• 依托单位: BENAROYA RESEARCH INST AT VIRGINIA MASON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-18 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8208890
• 关键词: Blood; Transcriptional; Biomarker; Profiles; Category

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.

描述（由申请人提供）：生物武器，以及自然发生的新出现和再出现的传染病，是对美国人口安全的最大威胁之一。由于ABC类优先病原体在美国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，这一事实加剧了这种风险。因此，我们建议通过与在世界上造成大量发病率和死亡率的地区工作的研究人员建立一个联盟来确定B类病原体的分子生物标志物特征。我们将通过开发基于宿主对感染的转录反应评估的诊断标记物，寻求一种替代和潜在的互补方法来直接检测病原体。事实上，我们已经证明，在感染的急性期，血液基因表达谱发生了巨大的变化，而且这些变化是病原体特异性的。在这个项目的背景下：(1)我们将收集特征明确的脓毒症（泰国孔凯大学伯克霍尔德菌）、持续性发热（布鲁氏菌属/法国马赛卢明免疫中心）和腹泻疾病（大肠杆菌、致病性弧菌菌株、志贺氏菌、沙门氏菌、空肠弯曲杆菌和Caliciviruses /墨西哥梅里达O'Horan总医院分子生物医学系cinvestv和微生物学研究实验室）患者的血液样本；(2)我们将利用全基因组血液转录筛选（48,000个转录本）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指标；(3)我们将使用集中转录分析验证候选血液标记物。总而言之，该项目将支持一个富有成效的研究人员网络，包括临床医生、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丰富的支持团队，他们将共同努力开发新的工具，以改善B类优先病原体引起的感染患者的管理。