Putting genomics to work

Another researcher developing tools to help make sense of the new wealth of genomic data is David Aanensen, director of the Centre for Genomic Pathogen Surveillance at the Wellcome Trust Sanger Institute and also a faculty member at Imperial College London. As he explained to Kat Arney, he’s developed a clever online platform called Microreact, which allows anyone to put in DNA information about pathogens such as bacteria or viruses, tracking how they’re spreading around the world and even working out what treatments they might be resistant to.

David - Well, I think one of the key challenges that has made its way into the media very strongly is antimicrobial resistance – so, the emerging and increasing resistance to antibiotics for particular species of bacteria. Clearly, what we need to do is to understand which strains are resistant, how were they acquiring resistance, and how and where they spread. If we can try and identify, and understand how they spread and where they're spreading – is it from humans to animals, is it from animals to humans, is it from different hosts? Do these hosts pass on between individuals, between countries, etc.? If we can try and understand the global spread of these antimicrobial resistant bugs, we can try and track them, and stop them spreading.

Kat - How are you trying to do that? What are some of the tools that you’ve got?

David - Well, we try and look at the use of whole genome sequencing. So if you can sample a bunch of bacteria, and then you sequence their genomes, you can compare how similar the genomes are to each other. You can use this to depict the relationships between them as a family tree. If we look at how more similar genomes are to each other, and whether those genomes are also resistant to particular antibiotics, we can then relate where those bacteria are or who those bacteria have been infecting, and whether we can use that information to understand who’s been spreading to who.

Kat - So, if you find related bacteria say, in Paris and in Cairo, that might tell you that either the bacteria spread from Cairo to Paris or Paris to Cairo, or something like that.

David - So these are some of the inferences that people might make. What we try and do is use what's known as bioinformatics which is computational methods of looking at the sequence to compare how similar things are to each other. Once we’ve got these family trees, we can look at whether the more closely related isolates potentially come from either the same place or different locations. We can use that information to make inferences about whether it could be a transmission from one country to another or one locale to another. We could also look for the presence of genes or genomic signatures in the genomes. If those signatures are present, it gives us an indication that that strain might be resistant to a particular antibiotic or not. Being able to do this on a global scale means that we can try and look towards monitoring the emergence of antimicrobial resistance and it spread both locally, nationally, and internationally. If we can do that then we can try and identify the emergence and then stop that spread.

Kat - How can we gather this kind of data? How can we gather and collect bacteria around the world?

David - Hospitals. People coming in to hospitals, swabbing individuals. Most often, if you go to a hospital and you have a bacterial infection then there will be some method to identify what species it is. But you can also then do standard antimicrobial resistance tests. This involves giving the antibiotic to the bacteria and seeing how many of them are killed and that gives you an indication of whether you can use the antibiotic to treat a patient or not. If we use whole genome sequencing, then we get a readout from the sequencer of a string of letters – A, C, Ts, and Gs. This is digital information so it could be stored very easily in databases. Those databases can be made easily available via the internet which means that anybody in the world essentially can get access to that information almost in real time. And we can then build on top of that intuitive interpretation and visualisation methods. So you can build trees online. You can add genomes from different countries to the same database and then we can enable anybody in the world to view the data as soon as it is produced. So we try and build methods on top of genomic sequence data that enable the information to be democratised, to make it universally accessible and available to anybody to identify whether they have more similar genome to ones that have been seen before.

Kat - You could imagine someone in the World Health Organisation or here in our NHS or the CDC in America going, “I want to know how this particular bacteria is spreading or how the flu virus is spreading this year or Zika virus” and you’ve got the visualisation tools that they could do that?

David - That's right. That’s what we’re trying to produce. We’re trying to produce open access systems that enable the collation of sequence data from anywhere in the world and the availability of that sequence data to anybody with any expertise to try and understand what's going on with the data. So this is clearly applicable for example in the UK, Public Health England, to understand the spread and they're using genome sequencing currently to understand the spread of gastrointestinal infections and other bacteria. The CDC, to understand the spread within the US, and of course, up to the level of the WHO. Genomic epidemiology has been used for understanding the spread of Ebola and Zika viruses. There are moves and efforts to actually produce these kinds of systems for exactly those kind of bugs.

Kat - What about if people, citizens, the general public want to get involved, because we must be covered with all sorts of bacteria and going around places where there are bugs. Is there any way that people could gather bacteria and help with this effort of tracking?

David - So I think that would be lovely. What would be ideal, it would be fantastic if we can monitor what's going on in a healthy population. So if we all carry bacteria ourselves, in the gut or on our skin. A classic example is Staph aureus that lots of us have on their skin and it doesn’t cause disease until it gets inside into the blood for example. If we could monitor what's going on with the healthy population, we could potentially use that information to spot the emergence of things that are potentially of greater risk to the public health. So actually, being able to swab yourself, send that off somewhere, have the genome sequenced. And for those background data to be available to anybody in the world to contextualise new information would be fantastic. What we need to do is to be giving genome sequencers away for free.

Kat - I love the idea of being a bacterial tourist – just go everywhere and swab while I'm away.

David - That would be pretty cool. Maybe not the best way to pitch a holiday to people, but that would be a wonderful thing to be able to do.

Kat - David Aanensen from the Wellcome Trust Sanger Institute. And if you have any germy genomes you’d like to analyse, you can have a play with Microreact at microreact.org

With more than a billion people living in India, not to mention the diaspora around the world, this kind of joined-up global genetic effort is only going to get more important in the future. And as Kat Arney discovered, the potential benefits are huge, according to Ewan Birney, director of the European Bioinformatics Institute in Cambridge and chair of the Global Alliance for Genomics and Health.

Ewan - Well, it’s really exciting. One of the reasons why is because it’s become remarkably cheaper to sequence DNA and we can now use that in healthcare. Previously, we only did it for a few people in a research context. Now, people can be sequenced because they're suspected of a particular genetic disease. But what that also means is we’ve got to realise all the research benefits. We have to be able to share that data between our healthcare systems. Not just between researchers but between people in different countries with different healthcare, rules and systems. That’s where the Global Alliance for Genomics and Health really comes in. What the Global Alliance aims to do is set up web protocols like the internet for genomic data sharing, but responsible genomic data sharing where the data will usually reside inside of the country of residence under the legal protections in each country.

Kat - Are there issues with things like formatting? I mean, those of us will remember the problems with, “Oh, that’s on a Mac, that’s on a PC…oh, I can't transfer these files.” Are there those same problems there with DNA?

Ewan - There are. Those are problems which really are just about engineering and removing. They do get in the way but that’s not the big problem. The bigger problem is having systems that work at the scale – this is petabyte, exabyte scale – so this is a physical scale of data problem. But there's also the interactions with the legal models present in every different country. Every country respects – in my experience – the value of research and the importance of sharing to create a better research on human health and they're positive about that. But when you're talking about whole populations, all of Denmark, all of the UK, all of France, you have to take a responsible attitude towards data sharing between these and researchers will have to adapt to a system which still allows research but in a responsible way of moving their code to the data sites rather than sharing data.

Kat - Ewan Birney from the European Bioinformatics Institute.