Estimating evolutionary and demographic parameters via ARG-derived IBD.

Inference of evolutionary and demographic parameters from a sample of genome sequences often proceeds by first inferring identical-by-descent (IBD) genome segments. By exploiting efficient data encoding based on the ancestral recombination graph (ARG), we obtain three major advantages over current approaches: (i) no need to impose a length threshold on IBD segments, (ii) IBD can be defined without the hard-to-verify requirement of no recombination, and (iii) computation time can be reduced with little loss of statistical efficiency using only the IBD segments from a set of sequence pairs that scales linearly with sample size. We first demonstrate powerful inferences when true IBD information is available from simulated data.

Detecting co-selection through excess linkage disequilibrium in bacterial genomes.

Population genomics has revolutionized our ability to study bacterial evolution by enabling data-driven discovery of the genetic architecture of trait variation. Genome-wide association studies (GWAS) have more recently become accompanied by genome-wide epistasis and co-selection (GWES) analysis, which offers a phenotype-free approach to generating hypotheses about selective processes that simultaneously impact multiple loci across the genome. However, existing GWES methods only consider associations between distant pairs of loci within the genome due to the strong impact of linkage-disequilibrium (LD) over short distances.

Estimating evolutionary and demographic parameters via ARG-derived IBD.

Inference of demographic and evolutionary parameters from a sample of genome sequences often proceeds by first inferring identical-by-descent (IBD) genome segments. By exploiting efficient data encoding based on the ancestral recombination graph (ARG), we obtain three major advantages over current approaches: (i) no need to impose a length threshold on IBD segments, (ii) IBD can be defined without the hard-to-verify requirement of no recombination, and (iii) computation time can be reduced with little loss of statistical efficiency using only the IBD segments from a set of sequence pairs that scales linearly with sample size. We first demonstrate powerful inferences when true IBD information is available from simulated data.

Four-week inhibition of the renin-angiotensin system in spontaneously hypertensive rats results in persistently lower blood pressure with reduced kidney renin and changes in expression of relevant gene networks.

Aims: Prevention of human hypertension is an important challenge and has been achieved in experimental models. Brief treatment with renin-angiotensin system (RAS) inhibitors permanently reduces the genetic hypertension of the spontaneously hypertensive rat (SHR). The kidney is involved in this fascinating phenomenon, but relevant changes in gene expression are unknown.

Fast and accurate joint inference of coancestry parameters for populations and/or individuals.

We introduce a fast, new algorithm for inferring from allele count data the FST parameters describing genetic distances among a set of populations and/or unrelated diploid individuals, and a tree with branch lengths corresponding to FST values. The tree can reflect historical processes of splitting and divergence, but seeks to represent the actual genetic variance as accurately as possible with a tree structure. We generalise two major approaches to defining FST, via correlations and mismatch probabilities of sampled allele pairs, which measure shared and non-shared components of genetic variance.