The Iqbal lab works on methods for studying the DNA (the genome) of different organisms, and to compare the genomes of different individuals. For example, we might compare the DNA of Plasmodium parasites that cause drug-resistant malaria with DNA from those that are susceptible to drug treatment. Among other things, this allows us to:
- Spot DNA regions that seem to be mutating particularly fast across the world, resulting in so much diversity that the human immune system cannot find a single common weakness in the invader.
- Track the spread of bacteria in hospitals or even in individuals. Pathogens accumulate more and more small genetic changes, or mutations, as time goes by. So the earlier ‘versions’ of the pathogen have genomes with fewer mutations, and the more recent ones have more. By comparing the genome sequences of the bacteria in all the people in a hospital ward where there is an MRSA outbreak, we can trace the progress of the infection from the first patient infected to the last, and learn more about how hospital infections spread.
We work on computational methods for detecting and representing genetic variation, particularly from high-throughput sequencing data. There are many situations where genomic regions of considerable biomedical interest (eg the HLA genes in humans, many surface antigens in P. falciparum, and many antibiotic-resistance-conferring mobile elements in bacteria) are too diverse and have too complex evolutionary histories to be accessible to standard computational approaches. We develop algorithms and data structures for representing and detecting simple and complex genetic variation without using a reference genome. These methods are based on so-called 'de novo assembly', because they make no prior assumptions about the structure of the genome. Typically challenges involve dealing with large data volumes (efficiency of data structures and software implementation), developing appropriate algorithms to analyse complex variants, and incorporating ideas from population genetics into assembly. The initial publication of these methods was Iqbal et al, Nature Genetics (2012), and the software is called Cortex.
Applications to pathogen genomics
We work with collaborators to apply these methods to pathogens, to enable better surveillance of pathogen evolution (within host, within hospital and across the world) and to better understand variation in important drug-resistance and immune-target genes. We focus particularly on:
- The study of Plasmodium falciparum, the parasite responsible for malaria. The study of Plasmodium is particularly challenging for various reasons:
Worldwide diversity at a surface antigen of P. falciparum
Key collaborators are Dominic Kwiatkowski (MalariaGEN consortium), Derrick Crook (the Modernising Medical Microbiology Consortium) and Henk den Bakker (Cornell and New York State Department of Health)