Rapid metagenomics for diagnosis of bloodstream and respiratory tract nosocomial infections: current status and future prospects

Figures & data

Figure 1. Laboratory and bioinformatics steps of a typical CMg pipeline. A typical CMg pipeline starts with the DNA/RNA extraction from the clinical sample. Optional steps of host DNA depletion and WGA can be added before and after the extraction, respectively. This is followed by preparing the nucleic acid for sequencing - the choice of library prep procedure depends on the sequencing technology and the concentration and type of nucleic acid. Taxonomic assignment and AMR screening is then performed, after optional human read removal, providing pathogen and AMR gene lists

Table 1. Summary of the main CMg pipelines for the detection of BSIs

	Sensitivity	Specificity	Turnaround time	Microorganisms detected	Bioinformatics methods used	Sequencing Technology	References
Fraunhoffer Institute pipeline (Illumina)	63%	28%	24–30 hours	Bacterial, viral and fungal species	Sepsis indicating quantifier (SIQ) in-house tool	Illumina HiSeq	[28,31]
Fraunhoffer Institute pipeline (ONT)	Not reported	Notreported	<6 hours	Bacterial, viral and fungal species	Sepsis indicating quantifier (SIQ) in-house tool	ONT MinION	[35]
Karius® Test	94% vs BC (84.9% BC + Additional test)	63%	29 hours	Bacterial, viral and fungal species	Karius custom-built analysis pipeline	Illumina NextSeq500	[37–39]
iDTECTTM Dx Blood test	82%	70%	2–3 days	Bacterial and viral species	Score generator proprietary bioinformatics tool	Life Technologies Ion Proton	[49]

Table 2. Summary of the main CMg pipelines for the diagnosis of LRTIs

	Sensitivity	Specificity	Turnaround time	Microorganisms detected	Bioinformatics methods used	Sequencing Technology	References
Langelier et al. (short-reads)	100%	83%	Not reported	Bacterial, viral and fungal species	In-house with machine learning predictive model	Illumina HiSeq	[75]
Li et al. (short-reads)	89%	74%	Not reported	Bacterial, viral (DNA) and fungal species	In house based on Burrows-Wheeler alignment tool	BGISEQ-50	[78]
Yang et al. (long-reads)	100%	66%	6–8 hours	Bacterial and fungal species	Epi2ME ONT platform	ONT MinION	[76]
Charalampous et al. (long-reads)	100%	100%	6 hours	Bacterial and fungal species	Epi2ME ONT platform	ONT MinION	[57]

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