Variant antigen repertoires in Trypanosoma congolense populations and experimental infections can be profiled from deep sequence data with a set of universal protein motifs.

Silva Pereira, Sara, Casas Sanchez, Aitor ORCID: https://orcid.org/0000-0001-5237-1223, Haines, Lee ORCID: https://orcid.org/0000-0001-8821-6479, Absolomon, Kihara, Ogugo, Moses, Sanders, Mandy, Kemp, Steve, Acosta Serrano, Alvaro ORCID: https://orcid.org/0000-0002-2576-7959, Noyes, Harry, Berriman, Matthew and Jackson, Andrew P (2018) 'Variant antigen repertoires in Trypanosoma congolense populations and experimental infections can be profiled from deep sequence data with a set of universal protein motifs.'. Genome Research, Vol 28, pp. 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. [Abstract copyright: Published by Cold Spring Harbor Laboratory Press.]

Item Type:	Article
Subjects:	QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 573 Antigens WA Public Health > WA 30 Socioeconomic factors in public health (General) WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries WC Communicable Diseases > Tropical and Parasitic Diseases > WC 705 Trypanosomiasis
Faculty: Department:	Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1101/gr.234146.118
SWORD Depositor:	JISC Pubrouter
Depositing User:	Stacy Murtagh
Date Deposited:	25 Jul 2018 09:45
Last Modified:	27 Sep 2019 15:30
URI:	https://archive.lstmed.ac.uk/id/eprint/8973

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