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Course Informatics Guide
Viral genome sequencing and sequence-dependent detection methods have been applied to the diagnosis and management of viral infections for decades. However, the introduction of next-generation sequencing (NGS) technologies is transforming how clinical microbiology laboratories diagnose and manage infectious diseases. Whole genome sequencing (WGS) of hundreds of microbes can be undertaken in hours enabling real time genomics for diagnostics, transmission investigation and infection control.
This Genomics and Clinical Virology course combines practical hands-on laboratory and bioinformatics work with lectures by, and discussions with, leaders in this crucial, exciting, and expanding area. The course is aimed at virology researchers at PhD, postdoc or more senior level who have an interest in learning how to carry out NGS of viral genomes, and clinical and research scientists who are planning to implement NGS in clinical diagnostic laboratories. The course will concentrate on the application of cutting-edge genomic techniques that can be implemented now and explore new approaches that will enter practice in the near future.
What will I learn?
The practical part of the course will provide laboratory sessions that will focus on the preparation of sequencing libraries for metagenomics and PCR-based approaches with particular emphasis on how to improve the efficiency of viral NGS by undertaking variations in library preparation techniques such as target enrichment by probe hybridization and the use of long-read technologies.
Participants will gain practical experience in Linux/Unix command line usage, bioinformatics analysis of the output data with focus on quality control of NGS data, reference mapping and de novo assembly approaches, and downstream analyses such as phylogenetic inference and variants associated with drug resistance.
There will be lectures and demonstrations of the potential applications of NGS in clinical laboratories, limitations and pitfalls of the techniques and clinical case studies e.g. in infection control and outbreak investigations including the ongoing SARS-CoV-2 pandemic.
The course has been approved for 46 CPD credits by the Royal College of Pathologists.
This course will cover a wide range of cutting-edge viral WGS laboratory techniques and *bioinformatics analysis in practical classes, demonstrations or lectures. The programme will include:
- Background to viral WGS approaches
- Sample handling and preparation
- Library preparation techniques
- Target enrichment methods e.g. probe-based sequence capture or PCR-based
- Viral metagenomics
- Technique discrimination – the appropriate technique to use in different scenarios
- Next generation and third generation sequencing platforms
- Bioinformatics analysis including different viral genome assembly approaches, variant calling, viral metagenomics, multiple sequence alignment and phylogenetic inference.
- Data interpretation
- Validation and accreditation of viral WGS diagnostic service
- Case studies in outbreak investigation and infection control
After attending the course, participants should be able to:
- Carry out NGS including wet lab preparation and bioinformatic analysis of real samples
- Create sequencing libraries and analyse samples derived from patients with viral infections (e.g. SARS-CoV-2, HIV, HCV, EBOV, Zika)
- Evaluate how to improve the efficiency of NGS by carrying out variations in library preparation technique e.g. target enrichment
- Evaluate the pitfalls of NGS interpretation in clinical viral diagnostics
- Evaluate potential future applications of NGS in clinical diagnostic laboratories and appreciate the limitations of the technique
- Demonstrate how viral WGS can be used to inform transmission patterns and evaluate the effectiveness of interventions
- Apply Linux/Unix command line to perform bioinformatics tasks
- Construct whole genomes by means of de novo assembly of NGS data and use standard tools to perform reference mapping
- Generate consensus sequences and call variants
- Use metagenomics tools such as KRAKEN and Centrifuge to detect and identify viral pathogens
- Compute multiple sequence alignments and build phylogenetic trees to understand viral evolution and transmission dynamics
Please note: Bioinformatic training will include the use of Linux/Unix command-line. As such, a prerequisite for this course is the completion of a Linux introductory course – familiarity with Linux and the command line is recommended in order to get the most from this course. There are numerous online introductory tutorials to the Linux/Unix operating system and command line, including:
Course Organisers
- Nick Loman, University of Birmingham, UK
- Tamyo Mbisa, UK Health Security Agency, UK
- Emma Thomson, University of Glasgow, UK
- Sreenu Vattipally, University of Glasgow, UK
Course Instructors
- Anna da Silva Filipe, UK Health Security Agency, UK
- Richard Orton, University of Glasgow, UK
- Sunando Roy, University College, London, UK
- Charlotte Williams, University College, London, UK
- Sarah Buddle, University College, London, UK
- David Bibby, UK Health Security Agency, UK
- Joshua Quick, University of Birmingham, UK
- Samantha Lycett, University of Edinburgh, UK
Wellcome Connecting Science Team
- Alice Matimba, Head of Training and Global Capacity
- Amy Pass, Events Manager
- Cassandra Soo, Laboratory Courses Manager
- Aaron Dean, Laboratory Technical Officer
- Christopher Adamson, Laboratory Operations Officer
- Martin Asltett, Informatics Manager
- Vaishnavi Vikas Gangadhar, Informatics Technical Officer
The course data are free to reuse and adapt with appropriate attribution. All course data in these repositories are licensed under the Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0).
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