Virome metagenomics from clinical samples
This joint DPhil studentship, based between the Department of Biology at the University of Oxford and the Ellison Institute of Technology (EIT) Pathogen Program, will focus on metagenomic analysis of clinical samples. The project will involve developing and applying computational approaches to virome metagenomic data from patient cohorts to investigate the diversity, evolution and impact of viruses.
Viruses are the most abundant biological entities on Earth, yet much of the global virome remains uncharacterised. Similarly, the virome of the microcosm present even within a single clinical sample, and its biological consequences, are not well understood. Advances in metagenomic sequencing technology have made it possible to detect viruses directly from complex samples in an unbiased way [3,4]. This creates new opportunities to discover previously unknown viruses, understand the diversity of circulating viruses, and understand their biological roles. The work will build on ongoing research into virus evolution and host/pathogen interactions, developing and using computational and evolutionary approaches, to reveal the diversity and consequences of viruses obtained from clinical samples [1,2].
The student will generate and analyse virome metagenomic datasets from clinical respiratorty samples to identify and characterise circulating viruses, including retroviruses as well as a broad range of RNA and DNA viruses. The approach will be unbiased, characterising both known and unknown viruses. A central component of the project will be the development, evaluation and application of computational workflows for viral sequence detection, genome assembly, taxonomic classification and evolutionary analysis. These approaches will be used to assess and compare viral diversity within and between clinical samples and cohorts. These will be used to investigate patterns of viral evolution [1,2]. Depending on the direction of the research, there may also be opportunities to analyse viromes from animal, environmental, or wastewater samples, providing insights into the processes that underpin pathogen emergence and persistence. The student will also have the opportunity to acquire wet lab skills in sample preparation and metagenomic sequencing [3].
Key deliverables will include: (a) validated computational workflows for detecting, assembling and classifying viruses from metagenomic sequencing data; (b) characterised virome datasets from selected clinical cohorts, including identification of known and candidate novel viruses; (c) evolutionary and comparative analyses describing viral diversity and relationships across samples or cohorts; and (
d) dissemination of the resulting methods and biological findings through conference presentations and peer-reviewed publications.
- Markov, P.V., Ghafari, M., Beer, M. et al. The evolution of SARS-CoV-2. Nat Rev Microbiol 21, 361–379 (2023). https://doi.org/10.1038/s41579-023-00878-2
- Katzourakis A, Gifford RJ (2010) Endogenous Viral Elements in Animal Genomes. PLOS Genetics 6(11): e1001191. https://doi.org/10.1371/journal.pgen.1001191
- Charalampous, T., Kay, G.L., Richardson, H. et al. Nanopore metagenomics enables rapid clinical diagnosis of bacterial lower respiratory infection. Nat Biotechnol 37, 783–792 (2019). https://doi.org/10.1038/s41587-019-0156-5
- Themoula Charalampous, Adela Alcolea-Medina, Luke B. Snell, Christopher Alder, Mark Tan, Tom G. S. Williams, Noor Al-Yaakoubi, Gul Humayun, Christopher I. S. Meadows, Duncan L. A. Wyncoll, Richard Paul, Carolyn J. Hemsley, Dakshika Jeyaratnam, William Newsholme, Simon Goldenberg, Amita Patel, Fearghal Tucker, Gaia Nebbia, Mark Wilks, Meera Chand, Penelope R. Cliff, Rahul Batra, Justin O’Grady, Nicholas A. Barrett, Jonathan D. Edgeworth, Routine Metagenomics Service for ICU Patients with Respiratory Infection, American Journal of Respiratory and Critical Care Medicine, Volume 209, Issue 2, January 2024, Pages 164–174, https://doi.org/10.1164/rccm.202305-0901OC

