Public Health England Initiative for Infectious Disease Genomics

By Catherine Arnold

18 August 2014


Public Health England (PHE) is at the forefront of a genomic revolution in the study of infectious disease transmission for public health in the UK by developing a substantial capability for routine microbial genome sequencing and analysis, focused on organisms causing infection. The aim is to help us understand how different bacteria or viruses cause disease, how they are transmitted and how they are related, and thereby inform how to break the cycle of infection.

In 2003, the Human Genome Project delivered the first complete human genome sequence, requiring collaboration between expert centres across the globe, taking over ten years to complete and at a cost of around three billion dollars. However, Developments in DNA sequencing technology, often collectively termed Next Generation Sequencing or NGS, have produced a revolutionary increase in the number and speed at which genomes can be sequenced and at a reduced cost. In collaboration with the NHS and academia, this presented PHE with a fantastic opportunity to use whole genome sequencing in identifying and comparing bacteria and viruses causing disease in humans.   

PHE is working collaboratively with a number of high profile translational research programmes, including Modernising Medical Microbiology  led from Oxford and with researchers based at the Sanger Institute and Cambridge.  Methods have been developed for tuberculosis, Staphylococcus aureus, Clostridium difficile and other pathogens. The recently awarded NIHR Health Protection Research Units also include important PHE collaborations with academia that use whole genome sequencing to investigate antibiotic resistance. Part of the investment by PHE has been to establish a state of the art sequencing capability at PHE in Colindale and the PHE Pathogen Genomics Service was launched at the beginning of April 2014. Following development of the complicated infrastructure required, together with initial validation work to start to create the contextual data required for effective genomic analysis, the central PHE Pathogen Genomics Service has sequenced upwards of 5,000 genomes since launch. PHE has invested in recruiting highly qualified laboratory and bioinformatics staff and is now developing methods for:

  • Rapid identification of bacterial and viral pathogens (organisms causing disease)
  • Comparing pathogens at a forensic level so that we can understand their relationship (i.e. linked in a transmission chain or an outbreak or emergence of new strains.)
  • Being able to predict whether a particular strain is going to be more infectious or cause more serious disease.

NGS generates information from virtually the whole genome and because of this there is the potential to do all of the above in one process potentially replacing several different methods used currently  in a shorter time and providing a faster service and greater value for money. These approaches are already changing the way we investigate outbreaks of infectious disease. They give us detailed information about the infection and, when combined with good epidemiological information, provide a powerful tool for more effective public health intervention to prevent ongoing transmission and to pinpoint and eliminate sources of contamination in the food chain.  Recently, these techniques have been applied in PHE to investigate outbreaks of Salmonella, E. coli O157, shigella, invasive group A streptococcus, Listeria, waterborne Pseudomonas and TB.

As part of the 100,000 Genomes Project, PHE is currently working collaboratively with academic partners to develop and deploy whole genome sequencing methods into service in diagnostic laboratories for tuberculosis, HIV and Hepatitis C.

As this is a completely new area for public health, a huge amount of development work and validation has been carried out to ensure that this technology can deliver an effective service. We have had to develop new ways of working across normally discrete disciplines to ensure reliable and reproducible delivery of the NGS data, with relevant additional data and quality metrics. Virtually all of these processes are automated and all sample processing needs to be auditable and traceable throughout.

As with any new technology, there are several caveats.  Firstly, we need to have some caution in interpretation of results at this early stage. Their use is just one component of an investigation along with current ‘gold standard’ methods and good epidemiological information. We need to do a lot more work to understand how strains of bacteria and viruses undergo genetic change within an individual during the course of infection and how these are transmitted to others. 

Due to ease of international travel, infection is a global issue and we need to link with other national and international initiatives to compile the datasets and information that we need to understand this and PHE continues to forge these links. We need to develop the informatics and bioinformatic capabilities to manage, store and share this data and to link them effectively to clinical and epidemiological datasets. The global community needs to develop a completely new naming system for genomes in order to be able to share information across international boundaries for maximum benefit to all.

We also have to accept that this is a rapidly moving field, that new technologies are emerging that will complement or perhaps replace currently available approaches in subsequent years.  While the potential to have near-patient whole genome sequencing of infectious agents direct from clinical samples exists, the technology needs at least one or two more iterations before this is likely to happen.  

This is a revolutionary period of development for public health microbiology and PHE’s investment in genomics puts the UK in a very strong position to lead the development of genomic and related technologies for better health outcomes and responses in cases of infection. 

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