UltraSEQ, a Universal Bioinformatic Platform for Information-Based Clinical Metagenomics and Beyond

Applied metagenomics is a powerful emerging capability enabling the untargeted detection of pathogens, and its application in clinical diagnostics promises to alleviate the limitations of current targeted assays. While metagenomics offers a hypothesis-free approach to identify any pathogen, including unculturable and potentially novel pathogens, its application in clinical diagnostics has so far been limited by workflow-specific requirements, computational constraints, and lengthy expert review requirements. To address these challenges, we developed UltraSEQ, a first-of-its-kind accurate and scalable metagenomic bioinformatic tool for potential clinical diagnostics and biosurveillance utility. Here, we present the results of the evaluation of our novel UltraSEQ pipeline using an in silico-synthesized metagenome, mock microbial community data sets, and publicly available clinical data sets from samples of different infection types, including both short-read and long-read sequencing data. Our results show that UltraSEQ successfully detected all expected species across the tree of life in the in silico sample and detected all 10 bacterial and fungal species in the mock microbial community data set. For clinical data sets, even without requiring data set-specific configuration setting changes, background sample subtraction, or prior sample information, UltraSEQ achieved an overall accuracy of 91%. Furthermore, as an initial demonstration with a limited patient sample set, we show UltraSEQ's ability to provide antibiotic resistance and virulence factor genotypes that are consistent with phenotypic results. Taken together, the above-described results demonstrate that the UltraSEQ platform offers a transformative approach for microbial and metagenomic sample characterization, employing a biologically informed detection logic, deep metadata, and a flexible system architecture for the classification and characterization of taxonomic origin, gene function, and user-defined functions, including disease-causing infections.

Automated summary

Applied metagenomics, a hypothesis-free approach for identifying pathogens, has been limited in its application in clinical diagnostics due to workflow-specific requirements and computational constraints. To address these challenges, UltraSEQ, a transformative metagenomic bioinformatic tool, was developed and successfully demonstrated accurate detection and characterization of microbial samples, including disease-causing infections.