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Genomics is the study of the complete DNA sequence, for example of a particular parasite, allowing us to analyse its evolution and the impact of human interventions. Alongside clinical date, we use genomics to identify mutations that are markers for drug resistance. Mapping out drug resistance then helps inform elimination programmes.

My name is Olivo Miotto and I work on malaria genomics. I’m based at the Mahidol Oxford Research Unit in Bangkok in Thailand.

Genomics is the study of the complete DNA in a particular parasite, and actually it has made a big difference in a lot of diseases. For example, in malaria when we study parasite genomes, we can determine the factors that make them for instance resistant to drugs or make them invade the immune system so it’s useful for designing vaccines. We can also study the human genome and identify what makes certain people less prone to develop the disease or more prone to develop it in a severe form. 

The way to explain genomic epidemiology is basically to think of human populations: when human populations migrate around the planet, they intermix; they change; they adapt to their environment; they diversify. Similarly, parasite populations do the same with one big difference, that a parasite life cycle is very short compared to a human life cycle. What takes millions of years to happen in a human population, takes only a few seasons to happen in a parasite population. This means that we can study parasite evolution almost in real time as it happens, and this is very convenient because often parasites evolve precisely because of human intervention.

Studying the evolution of the parasite allows us to find out what has happened and what is the result of our intervention. A typical pattern of evolution is that in a certain population you’d normally expect the genetic make up to be very varied. That’s the same amongst humans: you generally expect children to look a bit different from their parents and so on. Sometimes we find populations of parasites where this diversity is no longer there, they have either expanded clonally as we say so that they all kind of look identical, or perhaps only a certain area of the genome has been transferred across to all parasites. What we then suspect is that there is some evolutionary selection that’s on going, and we drill into those signals to identify what’s happening.

Over the last few years, genomics is one of the fields that has most changed and that has most evolved in science. Suffices to say that the first genome sequence of malaria parasite was in 2002, and now we’re in 2018 and we are literally routinely sequencing thousands of genomes at the cost of about tens of dollars each. This means that we can actually conduct very large scale studies over quite an extensive geographical reach, and we can now get a fairly subtle phenomena that we can observe within the genome.

Genomic epidemiology starts from the field - we base our observations on the parasites that circulate in the field. From the very start it has a translational goal which is to describe what actually is infecting people. In order to do this we compare thousands of genomes together with the clinical data that comes with them in order to identify what mutations are markers for this resistance. Once we’ve done that, that enables us to monitor the drug resistance mutations that circulate in the countries. This is precisely what we do: we get a small blood spot from every patient in the health centres across the country, we analyse them and we map out drug resistance in the country. This data goes back directly to the National Malaria Control programmes that are doing the elimination work, and hopefully helping them in their decision making.

Olivo Miotto

Genomic epidemiology

Professor Olivo Miotto translates the massive quantities of data produced by genome sequences into meaningful knowledge about Plasmodium falciparum. Determined directly from patients blood samples, the parasite genetic code is mapped in geographical, ecological and historical contexts. Genomic epidemiology aims to monitor P. falciparum evolution, so that humanity can keep steps ahead of the parasite.

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