A Rapid, Blood RNA Assay for the Diagnosis of Acute Respiratory Infections

用于诊断急性呼吸道感染的快速血液 RNA 测定

• 批准号: 8522996
• 负责人: Neil A Fanger
• 金额: $ 15万
• 依托单位: VIRTICI, LLC
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2014-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8522996
• 关键词: Rapid; Blood; RNA; Assay; Diagnosis

DESCRIPTION (provided by applicant): Acute respiratory infections (ARIs) represent a major cause of morbidity and mortality in the world1. About 20% of all deaths in children younger than 5 years of age are due to ARIs, with among those 90% attributed to pneumonia. This translates into approximately 150 million cases of pneumonia, with between 11-20 million children hospitalized, and more than 2 million dying from the disease (WHO). Even in the US, influenza and pneumonia are the eighth leading cause of death, the majority of which are infants and the elderly (American Lung Association). The ability to identify etiological agents of respiratory infections remains inadequate. Indeed, there are major obstacles: 1) bacteria and viruses are not always present in samples; 2) determination of infectious agent can take days; and 3) multiple tests are often required to determine source. Moreover, current tests for diagnosis are poor at assessing disease severity and, to date, only a few studies have examined the usefulness of biomarker panels that might prove beneficial in the differentiation between bacterial and viral respiratory tract infections2. Such diagnostic obstacles can delay initiation o appropriate therapy, resulting in unnecessary morbidity, death, and healthcare costs3. Rapid advances in genomics research can be leveraged to dramatically improve the management of ARIs. Recently, we developed modular analysis approaches to evaluate whole genome blood microarray profiles from 410 samples comprised of patients clinically diagnosed with ARIs and healthy controls. The meta-analysis identified 10 gene sets (or modules) that were able to discriminate between bacterial and viral agents responsible for ARIs with high accuracy. Our goal is to develop AResT (Acute Respiratory-related Transcripts), an innovative multivariate RNA assay designed for rapid triage of patients with ARIs. The first step in the development process is to reduce the current number of transcript targets within these 10 modules (n=694) while enabling the use of a PCR-based detection method, and improve the scoring algorithm against an independent set of blood samples from patients diagnosed with well-characterized ARIs. The specific aims are to: 1) validate a PCR-based multivariate RNA profiling assay using banked patient samples; 2) improve the scoring algorithm while determining the minimum probe set; and 3) compare AResT test accuracy against commonly used blood biomarkers PCT and CRP.

描述（由申请方提供）：急性呼吸道感染（阿里斯）是全球发病率和死亡率的主要原因1。在所有5岁以下儿童的死亡中，约有20%是由于阿里斯，其中90%是由于肺炎。这意味着大约1.5亿例肺炎病例，1100万至2000万儿童住院，200多万人死于这种疾病（世卫组织）。即使在美国，流感和肺炎也是第八大死亡原因，其中大多数是婴儿和老年人（美国肺脏协会）。确定呼吸道感染病原体的能力仍然不足。事实上，存在主要障碍：1）细菌和病毒并不总是存在于样品中; 2）确定传染源可能需要数天时间; 3）通常需要多次测试来确定来源。此外，目前的诊断测试在评估疾病严重程度方面很差，到目前为止，只有少数研究检查了生物标志物组的有用性，这些生物标志物组可能有助于区分细菌和病毒呼吸道感染2。这些诊断障碍可能会延迟适当治疗的开始，导致不必要的发病率，死亡和医疗保健费用3。基因组学研究的快速进展可以用来显著改善阿里斯的管理。最近，我们开发了模块化的分析方法来评估410个样本的全基因组血液微阵列谱，这些样本包括临床诊断为阿里斯的患者和健康对照。荟萃分析确定了10个基因组（或模块），能够区分细菌和病毒因子之间的阿里斯与高精度。我们的目标是开发ARestT（急性呼吸相关转录本），这是一种创新的多变量RNA检测方法，旨在对阿里斯患者进行快速分诊。开发过程中的第一步是减少这10个模块中的转录物靶标的当前数量（n=694），同时启用基于PCR的检测方法，并针对诊断为特征明确的阿里斯患者的独立血液样本集改进评分算法。具体目标是：1）使用库存患者样本验证基于PCR的多变量RNA分析测定; 2）在确定最小探针集的同时改进评分算法; 3）将AResT检测准确性与常用血液生物标志物PCT和CRP进行比较。