richer countries to identify the extent of drug resistance. 'The complete genome of every Mycobacterium tuberculosis sample isolated from a patient in England [has been] sequenced at one of the Public Health England labs', he adds. 'Detailed bioinformatics analysis of these genomes enables us to track the spread of resistance.'
Fighting malaria Dominic Kwiatkowski, of both the Sanger Institute and the University of Oxford has been studying another global infectious killer, malaria, since the 1980s when he worked as a paediatrician in West Africa. 'We were trying to find out what made some children much more susceptible to malaria than others, and we thought that genetics might provide useful insights.' He now heads the genomic epidemiology network MalariaGEN, with a large group of researchers and collaborators studying the interplay between the three genomes that determine malaria susceptibility: the malaria parasite, its vector the Anopheles mosquito, and its human host. MalariaGEN is co- funded by the Wellcome Trust and the Gates Foundation to connect scientists and clinicians working in malaria- endemic countries with state- of-the-art equipment and expertise for analysis of these three genomes. Kwiatkowski’s team was
the first to use genome-wide association techniques to study human resistance to
“Detailed bioinformatics analysis of these genomes enables us to track the spread of resistance throughout the country”
malaria; a computationally challenging problem due to the great genetic diversity of human populations in Africa. This network, also, is
investing in capacity building throughout malaria-endemic regions, training local scientists to monitor the molecular evolution of malaria parasites by establishing in-country sequencing. 'Evolution moves fast, so it is possible to detect evolutionary pressure from patterns of genetic variance and predict resistance before it takes hold, rather like deducing the movement of stars from their red shift', says Kwiatkowski. These predictions can, again, help make sure that the right treatment is delivered to the right patients at the right time. They also contribute to the search for novel drugs. In some ways, the third genome – that of the vector – is considered the most intractable. 'Studying mosquito genomics is difficult because their genomes are so diverse', adds Kwiatkowski. 'You will typically find five million base differences between the maternal and paternal genomes of an individual mosquito, and this level of diversity makes genome assembly in these species one of the most complex current problems in all computational genomics'. It is, at least, a task that can benefit from economies of scale: all mosquito genome sequences, like parasite and patient sequences, are uploaded to the cloud where they can be compared to the complete global dataset. It is self-evident that
infectious diseases respect no boundaries. If epidemic outbreaks and endemic diseases are to be monitored successfully, let alone controlled, scientists and clinicians must cross boundaries too: between disciplines as well as between nations. The emerging science of computational molecular epidemiology already has a major part to play.
www.scientific-computing.com | @scwmagazine
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