Enabling comprehensive diagnosis of sub-acute infection in chronic respiratory disease via high sensitivity next generation sequencing

通过高灵敏度下一代测序实现慢性呼吸道疾病亚急性感染的全面诊断

• 批准号: 10460284
• 负责人: Roland Marcus
• 金额: $ 100万
• 依托单位: PEAK DIAGNOSTIC PARTNERS LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-17 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10460284
• 关键词: Acute; Algorithms; Asthma; Automobile Driving; Biological Assay; CLIA certified; Chronic Obstructive Pulmonary Disease; Chronic lung disease; Clinical; Clinical Research; Collaborations; Colorado; Computer Systems; Computer software; Computerized Medical Record; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Future; Goals; Gold; Health; Healthcare Systems; Hospitalization; Individual; Infection; Information Systems; Infrastructure; Institution; Knowledge; Laboratories; Lung; Lung infections; Medical Care Costs; Metagenomics; Methodology; Methods; Microbe; Microbiology; Molecular; Online Systems; Outcome; Pathology; Patients; Pharmaceutical Preparations; Phase; Physicians; Population; Prognosis; Quality of life; Reporting; Research; Research Activity; Respiratory Tract Infections; Risk; Sampling; Secure; Sensitivity and Specificity; Series; Small Business Innovation Research Grant; Source; Symptoms; System; Systems Integration; Technology; Test Result; Testing; Time; Treatment Effectiveness; Validation; Viral; Visualization; Writing; acute infection; base; care costs; chronic respiratory disease; clinical database; clinically relevant; cloud based; cost; data integration; design; diagnostic assay; diagnostic tool; diagnostic value; disease phenotype; disorder control; experience; health care service organization; improved; insight; learning algorithm; metagenomic sequencing; microbial; molecular sequence database; next generation sequencing; novel; novel diagnostics; pathogen; pathogenic microbe; personalized medicine; phase 1 study; productivity loss; provider adoption; relational database; research clinical testing; respiratory pathogen; scale up; software systems; statistical learning; targeted sequencing; technological innovation; tool; treatment strategy; web portal

ABSTRACT Sub-acute lung infections are increasingly recognized as drivers of poor symptom control among a subset of individuals with chronic lung disease, estimated to be more than 2 million in the US for Asthma and COPD patients. When these sub-acute infections are diagnosed and treated appropriately, chronic lung disease patients can convert from moderate/severe to a milder disease phenotype, requiring lower medication to achieve better health at a significantly lower cost. Current gold-standard diagnostics for sub-acute infection rely on decades-old technology that can take weeks to complete, have limited sensitivity, and are limited in the type and number of microbes that can be screened by a single test. Thus, a critical gap exists due to the inability of current diagnostics to comprehensively and accurately detect microbial pathogens in low-burden clinical samples, which is a significant barrier to improved clinical outcomes in chronic lung disease. We have thus developed a comprehensive next generation sequencing (NGS) panel for detection and identification of microbes. Our Phase I studies have demonstrated the feasibility of our diagnostic tool for application to subclinical respiratory infections and its superiority to both microbiological and molecular approaches to diagnosis. Our NGS diagnostics (Dx) panel is a significant technological innovation over current methodology; the Dx panel utilizes samples directly from the patient (rather than relying on cultures), provides greater sensitivity than qPCR or meta-genomic sequencing approaches and screens for the presence of tens of thousands other microbes in a single assay. These features are possible due to our Dx panel design in addition to proprietary laboratory and analysis workflows. The long-term goal of this project is to provide novel clinical tools for the detection of low- burden microbial infections driving disease pathology, symptomology, and exacerbations in chronic lung disease populations. In this Phase II, we will develop a data integration system to 1) deploy our diagnostic test in healthcare organizations to drive physician adoption, 2) build data and apply algorithms necessary to expand the impact and value-based reimbursement of our assay. Our Aims are to 1) develop a cloud-based commercial software system for data receipt, storage, analysis and clinical reporting at scale, 2) integrate our software system into the clinical workflow at our clinical partners, and 3) develop a web-based visualization portal for test results and build the infrastructure for use of advanced statistical learning algorithms. This integrated system will drive the development and application of personalized medicine approaches for diagnosis and treatment guidance currently missing in chronic lung disease. The total market for this diagnostic is the set of chronic lung disease patients with uncontrolled symptoms who could be screened for sub-acute infections. Our competitive advantages include improved sensitivity, comprehensive microbe detection, streamlined analysis, and treatment effectiveness insights within a single assay.

摘要 亚急性肺部感染越来越多地被认为是一个子集中症状控制不良的驱动因素， 患有慢性肺病的人，估计在美国有超过200万人患有哮喘和COPD 患者当这些亚急性感染得到诊断和适当治疗时， 患者可以从中度/重度疾病表型转化为较轻的疾病表型， 以更低的成本获得更好的健康目前亚急性感染的黄金标准诊断依赖于 几十年前的技术，可能需要数周才能完成，灵敏度有限，类型有限， 可以通过单一测试筛选的微生物数量。因此，由于电流的不可能， 诊断，以全面准确地检测低负荷临床样本中的微生物病原体， 是改善慢性肺部疾病临床结局的重要障碍。因此，我们开发了一个 用于检测和鉴定微生物的全面的下一代测序（NGS）板。我们的相位 I研究已经证明了我们的诊断工具应用于亚临床呼吸系统疾病的可行性。 感染和它的优越性，微生物和分子诊断方法。我们的NGS 诊断（Dx）面板是对当前方法的重大技术创新; Dx面板利用 直接来自患者的样本（而不是依赖于培养物），提供比qPCR或 元基因组测序方法和屏幕上的存在数以万计的其他微生物在一个 单次测定。由于我们的Dx面板设计以及专有实验室和 分析工作流。该项目的长期目标是为检测低血糖提供新的临床工具。 微生物感染加重慢性肺病的疾病病理学、病理学和加重 人口。在第二阶段，我们将开发一个数据集成系统，以1）将我们的诊断测试部署在 医疗保健组织推动医生采用，2）构建数据并应用必要的算法， 我们分析的影响和基于价值的补偿。我们的目标是1）开发基于云的商业 用于大规模数据接收、存储、分析和临床报告的软件系统，2）集成我们的软件 系统纳入临床工作流程，在我们的临床合作伙伴，和3）开发一个基于Web的可视化门户网站，用于测试 结果，并建立使用先进的统计学习算法的基础设施。该综合系统将 推动个性化诊疗方法的开发和应用 目前缺乏对慢性肺病的指导。这种诊断的总市场是一套慢性肺 可以筛查亚急性感染的症状不受控制的疾病患者。我们的竞争 其优点包括提高灵敏度、全面的微生物检测、简化的分析和治疗 在一个单一的分析有效性的见解。