Metagenomic sequencing in clinical virology: advances in pathogen detection and future prospects

Carbo, E.C. (2023)

Doctoral Thesis

Metagenomics enables the detection of all the genetic material of organisms present in a sample, making it a pathogen-agnostic approach for detecting common and rare or novel pathogens that are not included in conventional testing⁠. Beforehand, a clinician does not need to have a hypothesis of what pathogen is expected, unlike traditional polymerase chain reaction (PCR) testing⁠.
This thesis is focusing on diagnostic yield, clinical findings, and enhancing technical opportunities in viral metagenomics⁠. The identification, typing, and quantification of viruses by means of viral metagenomics as a diagnostic tool are evaluated⁠. Technical aspects are appraised for improved sensitivity and specificity of the wet and dry (bioinformatic) lab components of viral metagenomics⁠. The use of a metagenomic protocol for virus discovery directly in a patient sample is assessed, and the best methods and approaches for performing genetic analysis of the SARS-CoV-2 virus are investigated⁠.
Viral metagenomic testing results in the identification of more viruses, therefore it is a valuable addition to current diagnostic test protocols⁠. Additionally, it is a useful test for virus discovery and monitoring during infectious disease outbreaks caused by novel viruses⁠.

• Metagenomics
• Virus
• Pathogen detection
• Next-generation sequencing
• Bioinformatics
• Virus discovery
• Load monitoring
• SARS-CoV-2

• All authors: Carbo, E.C.
• Supervisor: Kroes, A.C.M.
• Co-supervisor: Vries, J.J.C. de; Sidorov, I.A.
• Committee: Fischer, N.; Jong, M.D. de; Visser, L.G.; Snijder, E.J.; Claas, E.C.J.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2023-05-17
• ISBN (print): 9789082425741