Biology subjects

Kousathanas, A.

Publications and source records attributed to Kousathanas, A..

4 recordsLinked to original sources

bioRxiv2021

Innate immune pathways act synergistically to constrain RNA virus evolution in Drosophila melanogaster

Host-pathogen interactions impose recurrent selective pressures that lead to constant adaptation and counter-adaptation in both competing species. Here, we sought to study this evolutionary arms-race and assessed the impact of the innate immune system on viral population diversity and evolution, using D. melanogaster as model host and its natural pathogen Drosophila C virus (DCV). We first isogenized eight fly genotypes generating animals defective for RNAi, Imd and Toll innate immune pathways and also pathogen sensing and gut renewal pathways. Wild-type or mutant flies were then orally infected and DCV was serially passaged ten times. Viral population diversity was studied after each viral passage by high-throughput sequencing, and infection phenotypes were assessed at the beginning and at the end of the passaging scheme. We found that the absence of any of the various immune pathways studied increased viral genetic diversity and attenuated the viruses. Strikingly, these effects were observed in both host factors with antiviral properties and host factors with antibacterial properties. Together, our results indicate that the innate immunity system as a whole, and not specific antiviral defense pathways in isolation, generally constrains viral diversity and evolution.

evolutionary biology↗

bioRxiv2020

Integrative omics approach to identify the molecular architecture of inflammatory protein levels in healthy older adults

The molecular factors which control circulating levels of inflammatory proteins are not well understood. Furthermore, association studies between molecular probes and human traits are often performed by linear model-based methods which may fail to account for complex structure and interrelationships within molecular datasets. Therefore, in this study, we perform genome- and epigenome-wide association studies (GWAS/EWAS) on the levels of 70 plasma-derived inflammatory protein biomarkers in healthy older adults (Lothian Birth Cohort 1936; n = 876; Olink(R) inflammation panel). We employ a Bayesian framework (BayesR+) which can account for issues pertaining to data structure and unknown confounding variables (with sensitivity analyses using ordinary least squares- (OLS) and mixed model-based approaches). We identified 13 SNPs associated with 13 proteins (n = 1 SNP each) concordant across OLS and Bayesian methods. We identified three CpG sites spread across three proteins (n = 1 CpG each) that were concordant across OLS, mixed-model and Bayesian analyses. Tagged genetic variants accounted for up to 45% of variance in protein levels (for MCP2, 36% of variance alone attributable to one polymorphism). Methylation data accounted for up to 46% of variation in protein levels (for CXCL10). Up to 66% of variation in protein levels (for VEGFA) was explained using genetic and epigenetic data combined. We demonstrated putative causal relationships between CD6 and IL18R1 with inflammatory bowel disease, and between IL12B and Crohns disease. Our data may aid understanding of the molecular regulation of the circulating inflammatory proteome as well as causal relationships between inflammatory mediators and disease.

genomics↗

bioRxiv2017

The demographic history and mutational load of African hunter-gatherers and farmers

The distribution of deleterious genetic variation across human populations is a key issue in evolutionary biology and medical genetics. However, the impact of different modes of subsistence on recent changes in population size, patterns of gene flow, and deleterious mutational load remains unclear. Here, we report high-coverage exome sequencing data from various populations of rainforest hunter-gatherers and farmers from central Africa. We find that the recent demographic histories of hunter-gatherers and farmers differed considerably, with population collapses for hunter-gatherers and expansions for farmers, accompanied by increased gene flow. We show that purifying selection against deleterious alleles is of similar efficiency across African populations, in contrast with Europeans where we detect weaker purifying selection. Furthermore, the per-individual mutation load of rainforest hunter-gatherers is similar to that of farmers, under both additive and recessive models. Our results indicate that differences in the cultural practices and demographic regimes of African populations have not resulted in large differences in mutational burden, and highlight the beneficial role of gene flow in reshaping the distribution of deleterious genetic variation across human populations.

evolutionary biology↗

bioRxiv2017

ATLAS: Analysis Tools for Low-depth and Ancient Samples

SummaryPost-mortem damage (PMD) obstructs the proper analysis of ancient DNA samples and can currently only be addressed by removing or down-weighting potentially damaged data. Here we present ATLAS, a suite of methods to accurately genotype and estimate genetic diversity from ancient samples, while accounting for PMD. It works directly from raw BAM files and enables the building of complete and customized pipelines for the analysis of ancient and other low-depth samples in a very user-friendly way. Based on simulations we show that, in the presence of PMD, a dedicated pipeline of ATLAS calls genotypes more accurately than the state-of-the-art pipeline of GATK combined with mapDamage 2.0.\n\nAvailabilityATLAS is an open-source C++ program freely available at https://bitbucket.org/phaentu/atlas.\n\nContactDaniel.Wegmann@unifr.ch\n\nSupplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗