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London School of Hygiene & Tropical Medicine Malaria Centre

Malaria research in parasite biology

Genomic epidemiology using Plasmodium falciparum whole genome sequencing data.

LSHTM investigators:
Francesc Coll, Mark Preston, Nuno Sepulveda, David Baker, Teun Bousema, David Conway, Chris Drakeley, Cally Roper, Colin Sutherland & Taane Clark.
External collaborators:
Samuel Assefa, Thomas Otto, Magnus Manske, Susana Campino & Dominic Kwiatkowski (Wellcome Trust Sanger Institute, UK).

Next generation sequencing technologies are generating many millions of short sequences (reads).

These are leading to near complete Plasmodium falciparum (Pf) genomes, through alignment to the reference genome (3D7, 23Mb) and de novo assembly. Many hundreds of Pf isolates have been sequenced (e.g. Manske et al (2012)), including samples contributed by LSHTM PIs, and the resulting raw data are becoming publically available (e.g. Short read archive ERP000190). At the LSHTM we have established data analysis pipelines (Robinson et al 2011), and are currently involved in several areas of research, including: (i) cataloguing of structural variation across the Pf genome, (ii) estimating the multiplicity of infection, (iii) detecting regions under selective pressure, (iv) estimating recombination breakpoints and identifying important genetic motifs in hotspots,  (v) summarising Pf population structure and developing genetic barcodes for implementation in high throughput assays, and (vi) an assessment of Pf evolution using mitochondrial and apicoplast genomes.

To support this work, stand-alone software has been developed to view genomic variation (“VarB”), and identify and display regions under selection, as well as recombination breakpoints (“SelectionVista”). We have also developed web-based tools to view variants (e.g. “Malaria SNPVista”, see Figure).  Further information may be obtained from www.pathogenseq.org