Variant antigen profiling: a tool for genome-wide analysis of Variant Surface Glycoprotein diversity in Trypanosoma congolense.. Antigen diversity of T. congolense

Antigen variation is the mechanism through which African trypanosomes modulate the Variant Surface Glycoprotein (VSG) comprising their cell surface coat, resulting in chronic infection. Periodic switching of the expressed VSG, coupled with the host immune response, causes sequential expansion of parasite clones each expressing a serologically distinct VSG. Genome sequencing has revealed hundreds of VSG genes and this presents challenges for analysing VSG dynamics over space and time. We have developed a method for analysing VSG diversity in Trypanosoma congolense on a population scale using high-throughput sequencing data.Previously, we showed that T. congolense VSGs segregate into defined ‘phylotypes’, between which there is no evidence for recombination. Using forty T. congolense clinical isolates from six African countries, we have discovered that these phylotypes are universal and exhaustive. Exploiting this predictable repertoire, we developed the ‘Variant Antigen Profile’ (VAP) as a metric of VSG diversity. The VAP calculates the relative frequencies of distinct VSG ‘phylotypes’ from genomic or transcriptomic data, to rapidly describe the repertoire in a given strain or condition.