Eye-Path Resubmission

摘要 快速和精确的诊断对于全球抗击传染病至关重要。当诊断和治疗是 由细菌、真菌、病毒或寄生虫引起的迟发性传染病， 使人衰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， 在服务点的疾病对于临床医生计划治疗是至关重要的。快速DNA和 RNA测序已在多种疾病中被证明是一种鉴定病原体的方法， 覆盖范围和灵敏度。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，在满足可现场部署的快速诊断需求方面的挑战， 测序技术在全球医学中的应用受到了严重影响。为了满足这一需求， ChromoLogic LLC（CL）与华盛顿大学（UW）合作，提出开发眼- Path™。Eye-Path系统包含2个不同的模块：（1）自动化DNA和RNA制备 样品试剂盒子系统和（2）基于云的基因组测序分析软件，目前处于临床试验中 用于表征眼部感染。病原体鉴定子系统由宏基因组鉴定子系统组成。 检测，其包含上传到基于云的计算平台以进行实时测序的实时测序读数。 序列匹配该系统使用可扩展的宏基因组学比对研究工具（SMART），一种新的工具 由我们的合作者，华盛顿大学的Russell货车Gelder博士和他的 团队[5]检测DNA和RNA为基础的生命形式，包括细菌，真菌，寄生虫和病毒， 前所未有的细节。此外，该技术可应用于许多其他传染病， 微生物取样操作。在第一阶段，ChromoLogic将建立分析验证并提供 Eye-Path™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液样本， 识别.将提取的样本进行分区，以便使用下一代测序仪进行测序 （Illumina）和配备有EYE-Path生物信息学软件和样品的Oxford Nanopore技术。 处理.通过本研究获得的数据，我们将期望（1）评估Eye-Path™的分析有效性 作为实验室开发测试（LDT）进行CMS CLIA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).