Eye-Path Resubmission

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).