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.

Petri-plate, bacteria, and laser optical scattering sensor

“…Polymerase chain reaction (PCR) assay has been also applied to colonies (Colony PCR) for the detection of various bacterial ( Zimmermann et al., 2014 ; Daramroodi et al., 2018 ) and fungal ( Lau et al., 2008 ; Walch et al., 2016 ) pathogens. Recently, whole genome sequencing (WGS) of isolated colonies is also finding widespread application in food safety and clinical medicine ( Hasman et al., 2014 ; Joensen et al., 2014 ; Köser et al., 2014 ; Purushothaman et al., 2022 ).…”

The Swiss Pathogen Surveillance Platform – towards a nation-wide One Health data exchange platform for bacterial, viral and fungal genomics and associated metadata

“…The transmission of individual strains can be monitored across and among different human, animal and environmental sources – a concept also known as One Health [6]. The analysis of sequencing data requires bioinformatic tools to assemble, annotate and compare the genomes [7]. During the past 2 years of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, tremendous sequencing capacities for surveillance have been built in many institutions or at national levels, which have provided very rapid insights into the transmission dynamics and evolution of SARS-CoV-2 [8].…”

Comparative evaluation of 16S rRNA metagenomic sequencing in the diagnosis and understanding of bacterial endophthalmitis

“…Clinically, whole genome sequencing (WGS) and metagenomic analysis have been performed as diagnostic approaches 5. In postprocedure endophthalmitis, higher load of bacteria from WGS has worse visual prognosis 6.…”

“…If pathogens are detected in the early stage of sepsis, proper selection of antibiotics for treatment can reduce the mortality rate 11–13. There are few reports on the use of metagenomic analysis to identify causative pathogens of ocular infectious diseases from intraocular samples 1–6. Therapeutic intervention is required in cases of endophthalmitis, and analysis of the collected samples is considered to be useful for determining treatment strategies 1–4.…”