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Reverse immunodynamics: a new method for identifying targets of protective immunity.

ABSTRACT: Despite a dramatic increase in our ability to catalogue variation among pathogen genomes, we have made far fewer advances in using this information to identify targets of protective immunity. Epidemiological models predict that strong immune selection can cause antigenic variants to structure into genetically discordant sets of antigenic types (e.g. serotypes). A corollary of this theory is that targets of immunity may be identified by searching for non-overlapping associations of amino acids among co-circulating antigenic variants. We propose a novel population genetics methodology that combines such predictions with phylogenetic analyses to identify genetic loci (epitopes) under strong immune selection. We apply this concept to the AMA-1 protein of the malaria parasite Plasmodium falciparum and find evidence of epitopes among certain regions of low variability which could render them ideal vaccine candidates. The proposed method can be applied to a myriad of multi-strain pathogens for which vast amounts of genetic data has been collected in recent years.

SUBMITTER: Spensley KJ

PROVIDER: S-EPMC6377634 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Reverse immunodynamics: a new method for identifying targets of protective immunity.

Spensley Katrina J KJ Wikramaratna Paul S PS Penman Bridget S BS Walker Andrew A Smith Adrian L AL Pybus Oliver G OG Jean Létitia L Gupta Sunetra S Lourenço José J

Scientific reports 20190215 1

Despite a dramatic increase in our ability to catalogue variation among pathogen genomes, we have made far fewer advances in using this information to identify targets of protective immunity. Epidemiological models predict that strong immune selection can cause antigenic variants to structure into genetically discordant sets of antigenic types (e.g. serotypes). A corollary of this theory is that targets of immunity may be identified by searching for non-overlapping associations of amino acids am ...[more]

PMID: 30770839

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Project description:BackgroundStudies of natural animal populations reveal widespread evidence for the diffusion of novel behaviour patterns, and for intra- and inter-population variation in behaviour. However, claims that these are manifestations of animal 'culture' remain controversial because alternative explanations to social learning remain difficult to refute. This inability to identify social learning in social settings has also contributed to the failure to test evolutionary hypotheses concerning the social learning strategies that animals deploy.Methodology/principal findingsWe present a solution to this problem, in the form of a new means of identifying social learning in animal populations. The method is based on the well-established premise of social learning research, that--when ecological and genetic differences are accounted for--social learning will generate greater homogeneity in behaviour between animals than expected in its absence. Our procedure compares the observed level of homogeneity to a sampling distribution generated utilizing randomization and other procedures, allowing claims of social learning to be evaluated according to consensual standards. We illustrate the method on data from groups of monkeys provided with novel two-option extractive foraging tasks, demonstrating that social learning can indeed be distinguished from unlearned processes and a social learning, and revealing that the monkeys only employed social learning for the more difficult tasks. The method is further validated against published datasets and through simulation, and exhibits higher statistical power than conventional inferential statistics.Conclusions/significanceThe method is potentially a significant technological development, which could prove of considerable value in assessing the validity of claims for culturally transmitted behaviour in animal groups. It will also be of value in enabling investigation of the social learning strategies deployed in captive and natural animal populations.

Dataset Information

Reverse immunodynamics: a new method for identifying targets of protective immunity.

Publications

Reverse immunodynamics: a new method for identifying targets of protective immunity.

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