In December 2012, Prime Minister David Cameron announced the “100,000 Genome Project” where the personal DNA code (known as a genome) of up to 100,000 patients, or infections in patients, will be decoded over the next 5 years. This will help improve our understanding of disease, leading to better and earlier diagnosis and personalised healthcare. Based on expert scientific advice, the Department of Health prioritised sequencing of lung and paediatric cancer, rare diseases and infectious diseases, with infectious disease sequencing undertaken by Public Health England.
The word ‘genome’ is used to describe all the hereditary information of an organism. As the hereditary information coded within DNA is inherited by children from their parents, so too bacteria and viruses causing infectious disease pass their DNA from one generation to another.
Our work will help us to understand how different bacteria are related; whether they are the same strain; and tell us whether they carry genes for antimicrobial resistance.
DNA is in each cell of an organism and is essentially a long chain of millions or even billions of ‘nucleotides’. Nucleotides can be one of four different molecules and different patterns in the sequence of these four molecules define the differences between species and the members of those species.
Determining the sequence of nucleotides in DNA from any organism has been very difficult to do.
You are probably aware of the Human Genome Project which delivered the first complete human genome sequence in 2003. This required collaboration between expert centres across the globe, took over 10 years to complete and cost around three billion dollars. However, recent technological developments 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 presents PHE with a fantastic opportunity to use whole genome sequencing in identifying and comparing bacteria and viruses causing disease in humans. Part of the investment by PHE has been to establish a state of the art sequencing capability at PHE in Colindale. This is to provide the ‘PHE Pathogen Genomics Service’ which will be launched early in 2014. 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 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.
Potentially, Next Generation Sequencing can do all of this in one process, whereas several different methods would currently be used. Most importantly, it offers a faster service for the patient and is a more cost effective process for the taxpayer. These approaches are already changing the way we investigate outbreaks of infectious disease because they give us detailed information about the infection and, when combined with good epidemiological information, provide a powerful tool. Recently, these techniques have been applied in PHE to investigate outbreaks of Salmonella, E. coli O157, shigella and TB.
There are several caveats though, as with any new technology. 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.
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.
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.
The good news is that the investment in genomics puts the UK in a strong position to lead the development of genomic and related technologies for better health outcomes and responses in cases of infection.