Combination of Whole Genome Sequencing and Metagenomics for Microbiological Diagnostics

Abstract

Whole genome sequencing (WGS) provides the highest resolution for genome-based species identification and can provide insight into the antimicrobial resistance and virulence potential of a single microbiological isolate during the diagnostic process. In contrast, metagenomic sequencing allows the analysis of DNA segments from multiple microorganisms within a community, either using an amplicon- or shotgun-based approach. However, WGS and shotgun metagenomic data are rarely combined, although such an approach may generate additive or synergistic information, critical for, e.g., patient management, infection control, and pathogen surveillance. To produce a combined workflow with actionable outputs, we need to understand the pre-to-post analytical process of both technologies. This will require specific databases storing interlinked sequencing and metadata, and also involves customized bioinformatic analytical pipelines. This review article will provide an overview of the critical steps and potential clinical application of combining WGS and metagenomics together for microbiological diagnosis.

Keywords: antimicrobial resistance; bioinformatics; combination; database; epidemiology; metagenomics; surveillance; transmission; whole genome sequencing.

Figure 1

Decision tree for the selection of sequencing technology. The type of samples and research questions guide the selection of suitable sequencing strategies and sequencing platforms. The diamonds represent the checkpoints/questions, and the blue rectangles represent the sequencing strategies. * Sweep sequencing is a technique in which concurrent sequencing of multiple colonies at the same time is possible—this could also be considered a metagenomic approach.