Metagenomic sequencing for pathogen identification and analysis

PI(s)/Head responsible for the resource:

Jenny Welander

Host organisation(s):

Clinical Microbiology and Precision Medicine Laboratory, Linköping University Hospital

Resource description:

Metagenomic sequencing enables the detection of unusual or unexpected pathogens in patient samples where routine methods fail. In a collaboration between Clinical Microbiology and the Precision Medicine Laboratory at Linköping University Hospital, methodology for metagenomic sequencing has been developed and evaluated.

The newly developed capability enables sequencing of total RNA and DNA from patient samples to detect bacteria, viruses, fungi, and parasites without any need for culture or amplification with pathogen-specific reagents. The method is based on nucleic acid extraction, parallel RNA and DNA library preparation, and Illumina sequencing, followed by bioinformatic taxonomic classification using the nf-core/taxprofiler pipeline.

The method will be used to detect and analyse unusual pathogens in respiratory samples and skin lesions. In addition, the method will be used for the analysis of cerebrospinal fluid in CNS infections that cannot be diagnosed using other methods. With this technology development, the laboratory has an increased preparedness to monitor and quickly respond to future outbreaks and pandemics.

The capability is participating in a national collaboration within the Genomic Medicine Sweden (GMS) network to coordinate laboratory and bioinformatics development, and exchange control samples.

Continuation funding:

This capability received funding from the REPLPCM call to continue their work. Please see the PLP background information page for more information about the REPLPCM call. With this funding, the methodology is now being further developed and validated into a clinical routine method for analysis of samples of unknown etiology. So far, validation of the method has included RNA viruses, DNA viruses, bacteria, and fungi. Biologists, bioinformaticians, and medically responsible doctors are working together to further optimise the method and build experience around the interpretation of complex results. Additional bioinformatics tools are being evaluated to improve pathogen characterisation and to enable the analysis of antimicrobial resistance. The capability also aims to establish quicker sequencing using long-read technology to decrease the turn around time.

Contact information:

Jenny Welander
Clinical Microbiology and Precision Medicine Laboratory, Linköping University Hospital
Email: jenny.welander@regionostergotland.se