Variant antigen repertoires in Trypanosoma congolense populations and experimental infections can be profiled from deep sequence data using universal protein motifs



Pereira, Sara Silva, Casas-Sanchez, Aitor ORCID: 0000-0001-5237-1223, Haines, Lee R, Absolomon, Kihara, Ogugo, Moses, Sanders, Mandy, Kemp, Steve, Acosta-Serrano, Alvaro, Noyes, Harry ORCID: 0000-0002-0656-200X, Berriman, Matthew
et al (show 1 more authors) (2018) Variant antigen repertoires in Trypanosoma congolense populations and experimental infections can be profiled from deep sequence data using universal protein motifs. GENOME RESEARCH, 28 (9). 1383 - 1394.

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Abstract

African trypanosomes are vector-borne hemoparasites of humans and animals. In the mammal, parasites evade the immune response through antigenic variation. Periodic switching of the Variant Surface Glycoprotein (VSG) coat covering their cell surface allows sequential expansion of serologically distinct parasite clones. Trypanosome genomes contain many hundreds of VSG genes, subject to rapid changes in nucleotide sequence, copy number and chromosomal position. Thus, analysing, or even quantifying, VSG diversity over space and time presents an enormous challenge to conventional techniques. Indeed, previous population genomic studies have overlooked this vital aspect of pathogen biology for lack of analytical tools. Here we present a method for analysing population-scale VSG diversity in Trypanosoma congolense from deep sequencing data. Previously, we suggested that T. congolense VSG segregate into defined 'phylotypes' that do not recombine. In our dataset comprising 41 T. congolense genome sequences from across Africa, these phylotypes are universal and exhaustive. Screening sequence contigs with diagnostic protein motifs accurately quantifies relative phylotype frequencies, providing a metric of VSG diversity, called the 'Variant Antigen Profile'. We applied our metric to VSG expression in the tsetse fly, showing that certain, rare VSG phylotypes may be preferentially expressed in infective, metacyclic-stage parasites. Hence, variant antigen profiling accurately and rapidly determines VSG gene and transcript repertoire from sequence data, without need for manual curation or highly contiguous sequences. It offers a tractable approach to measuring VSG diversity across strains and during infections, which is imperative to understanding the host-parasite interaction at population and individual scales.

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 13 Sep 2018 09:33
Last Modified: 28 May 2020 15:11
DOI: 10.1101/gr.234146.118
Open Access URL: https://genome.cshlp.org/content/28/9/1383.full.pd...
Related URLs:
URI: http://livrepository.liverpool.ac.uk/id/eprint/3026223