Broad Detection of Infectious Agents in Blood by Microarrays and Deep Sequencing

通过微阵列和深度测序广泛检测血液中的传染性病原体

• 批准号: 8453427
• 负责人: Charles Yen Chiu
• 金额: $ 55.44万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8453427
• 关键词: Acute; Age; American; Anaplasma; Babesia; Bacteria; Biological Assay; Blood; Blood Cells; Blood donor; Blood-Borne Pathogens; Borrelia; Cessation of life; Chagas Disease; Characteristics; Clinical; Clinical Microbiology; Clinical Sensitivity; Cytomegalovirus; Dengue Virus; Detection; Diagnostic; Ehrlichia; Ensure; Epidemiology; Fever; Genome; Genomics; Geographic Locations; Geography; Goals; HIV; HIV-1; Headache; Hepatitis; Hepatitis B; Human Herpesvirus 4; Human Parvovirus B19; Human T-lymphotropic virus 1; Individual; Infection; Infectious Agent; Investigation; Laboratories; Leishmania; Link; Malaria; Metagenomics; National Heart, Lung, and Blood Institute; Pathogen detection; Pathogenicity; Patients; Plasma; Plasmodium; Prevalence; Probability; Public Health; Red Cross; Relative (related person); Research; Safety; Sampling; Scientist; Sensitivity and Specificity; Serologic tests; Serum; Surveillance Program; Technology; Testing; Transfusion; Transfusion-Transmitted Virus; United States; United States National Institutes of Health; Vascular blood supply; Viral; Viral Load result; Virus; Whole Blood; base; deep sequencing; design; follow-up; genome sequencing; liver transplantation; novel; novel virus; pathogen; public health relevance; repository; respiratory; screening; sex; tool; viral detection

DESCRIPTION (provided by applicant): Bloodborne infectious agents, including novel / emerging pathogens of concern, pose a continual threat to our blood supply and the safety of the 5 million transfusions performed annually in the United States. Here we propose to apply two state-of-the-art diagnostic technologies, a pan-viral microarray called the Virochip and massively parallel deep sequencing, to comprehensively identify infectious agents in blood. The Virochip will be expanded to cover bloodborne nonviral as well as viral pathogens, and we will rigorously assess analytical test characteristics (e.g. sensitivity, specificity, limits of detection, accuracy) for detection of pathogens associated with the most common bloodborne infections, including malaria, Chagas disease, HIV, hepatitis B/C, and dengue virus. The expanded Virochip and deep sequencing will then be used to launch a broad- spectrum surveillance program for bloodborne infectious agents. We will initially focus on analyzing serum samples from patients with nonA-E clinical hepatitis and deferred blood donors with post-donation acute illness such as fever - samples which carry a high a priori probability of harboring known / novel infectious agents. We will analyze random individual or pooled serum samples from donors matched by age, sex, and geographic location for infectious agents circulating in our blood supply. We will perform whole-genome sequencing and epidemiological screening by serology and PCR for any novel viruses identified in transfused blood. A major goal of this research is to assess the utility of Virochip and deep sequencing as comprehensive pathogen screening tools for ensuring transfusion safety. Identification of novel infectious agents in blood will also spur further detailed investigations into their epidemiology and pathogenicity.

描述（由申请人提供）：血源性感染因子，包括新的/新出现的关注病原体，对我们的血液供应和美国每年进行的500万次输血的安全性构成持续威胁。在这里，我们建议应用两种最先进的诊断技术，一种称为Virochip的泛病毒微阵列和大规模并行深度测序，以全面识别血液中的感染因子。Virochip将扩展到包括血液传播的非病毒和病毒病原体，我们将严格评估分析测试特性（例如灵敏度、特异性、检测限、准确性），以检测与最常见的血液传播感染相关的病原体，包括疟疾、恰加斯病、艾滋病毒、B/C型肝炎和登革热病毒。扩展后的病毒芯片和深度测序随后将用于启动针对血源性传染因子的广谱监测计划。我们最初将重点分析来自非甲-戊型临床肝炎患者和献血后急性疾病（如发热）的递延献血者的血清样本-这些样本携带已知/新型传染性病原体的先验概率很高。我们将分析来自年龄、性别和地理位置相匹配的献血者的随机个体或合并血清样本，以检测我们血液供应中循环的传染性病原体。我们将通过血清学和PCR对输血中发现的任何新型病毒进行全基因组测序和流行病学筛查。本研究的一个主要目标是评估病毒芯片和深度测序作为确保输血安全的全面病原体筛查工具的实用性。在血液中发现新的传染性病原体也将促使对其流行病学和致病性进行进一步的详细调查。