Eye-Path Resubmission

摘要 快速和准确的诊断对于全球抗击传染病至关重要。当诊断和治疗是 延迟性传染病可由细菌、真菌、病毒或寄生虫引起，可导致 使人虚弱或危及生命的疾病。因此，快速准确地鉴定传染病的病原学 服务点的疾病对于临床医生计划治疗至关重要。快速DNA和 RNA测序已在多种疾病中被证明是一种广泛的病原体识别方法 覆盖面广，敏感度极高。这样的系统能够识别任何基于核酸的生命形式 具有高吞吐量。然而，在满足现场可部署的快速诊断需求方面存在挑战 对全球医学中测序技术的采用产生了不利影响。为了满足这一需求， ChromoLogic LLC(CL)与华盛顿大学(UW)合作，提议开发Eye- Path™。Eye-Path系统包含两个不同的模块：(1)自动DNA和RNA制备 样本试剂盒子系统和(2)基于云的基因组测序分析软件，目前正在进行临床试验 在威斯康星州大学进行眼部感染的特征研究。病原体鉴定子系统由一个元基因组组成 包含实时测序读数的检测，上传到基于云的计算平台进行实时 序列匹配。该系统使用可扩展的元基因组学比对研究工具(SMART)，这是一种新的工具 由我们的合作者、华盛顿大学的Russell Van Geld博士和他的 团队[5]检测基于DNA和RNA的生命形式-包括细菌、真菌、寄生虫和病毒 史无前例的细节。此外，这项技术还可以适用于许多其他传染病和 微生物采样操作。在第一阶段，ChromoLogic将建立分析验证并提供 眼路™的初步临床验证数据。为了评估使用眼路的临床有效性，我们将 处理疑似眼内炎患者的玻璃体体液样本并进行实时病原体检测 身份证明。提取的样本将被分割，以便使用下一代测序仪进行测序 (Illumina)和配备了眼路生物信息学软件和样本的牛津纳米孔技术 正在处理。通过本研究获得的数据，我们将期望(1)评估Eye-Path™的S分析的有效性 对于CMS CLIA作为实验室开发的测试(LDT)进行审查。

Abstract Rapid and precise diagnosis is critical to combat infectious disease globally. When diagnosis and treatment is delayed, infectious disease, which can be caused by bacteria, fungi, viruses or parasites, can lead to debilitating or life-threatening illness. Therefore, rapid and accurate identification of etiology of infectious disease at the point-of-service is of paramount importance for clinicians planning treatment. Rapid DNA and RNA sequencing has been demonstrated in multiple diseases as a way to identify pathogen with broad coverage and exquisite sensitivity. Such systems are capable of identifying any nucleic acid-based lifeform with high throughput. However, challenges in meeting the need for field deployable rapid diagnosis has detrimentally impacted adoption of sequencing technology in global medicine. In order to address this need, ChromoLogic LLC (CL), in partnership with the University of Washington (UW), propose to develop the Eye- Path™. The Eye-Path system contains 2 distinct modules; (1) an automated DNA and RNA preparation sample kit subsystem and (2) a cloud-based genomic sequencing analysis software, currently in clinical trials at UW for characterizing ocular infections. The pathogen identification subsystem consists of a metagenomic detection that contains real-time sequencing reads uploaded to a cloud-based computing platform for real-time sequence matching. The system uses scalable metagenomics alignment research tool (SMART), a novel tool developed and licensed from our collaborator, Dr. Russell Van Gelder from University of Washington, and his team [5] to detect DNA and RNA-based life forms—including bacteria, fungi, parasites, and viruses with unprecedented detail. Furthermore, this technology can be applicable to many other infectious disease and microbial sampling operations. During Phase I, ChromoLogic will establish the analytical validation and provide preliminary clinical validation data of Eye-Path™. To assess for the clinical validity of using Eye-Path, we will process vitreous humor sample from patients with suspected endophthalmitis and perform real-time pathogen identification. The extracted samples will be partitioned for sequencing with a next generation sequencer (Illumina) and an Oxford Nanopore technology equipped with the EYE-Path bioinformatic software and sample processing. With the data obtained from this study, we will expect (1) assess Eye-Path™'s analytical validity for CMS CLIA review as a Laboratory Developed Test (LDT).