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Ultrafast genome-wide inference of pairwise coalescence times.

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Durbin, Richard 


The pairwise sequentially Markovian coalescent (PSMC) algorithm and its extensions infer the coalescence time of two homologous chromosomes at each genomic position. This inference is used in reconstructing demographic histories, detecting selection signatures, studying genome-wide associations, constructing ancestral recombination graphs, and more. Inference of coalescence times between each pair of haplotypes in a large data set is of great interest, as they may provide rich information about the population structure and history of the sample. Here, we introduce a new method, Gamma-SMC, which is more than 10 times faster than current methods. To obtain this speed-up, we represent the posterior coalescence time distributions succinctly as a gamma distribution with just two parameters; in contrast, PSMC and its extensions hold these in a vector over discrete intervals of time. Thus, Gamma-SMC has constant time-complexity per site, without dependence on the number of discrete time states. Additionally, because of this continuous representation, our method is able to infer times spanning many orders of magnitude and, as such, is robust to parameter misspecification. We describe how this approach works, show its performance on simulated and real data, and illustrate its use in studying recent positive selection in the 1000 Genomes Project data set.



Genome, Genomics, Haplotypes, Chromosomes, Algorithms, Models, Genetic, Genetics, Population

Journal Title

Genome Res

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Cold Spring Harbor Laboratory
Wellcome Trust (unknown)
Wellcome Trust (214300/Z/18/Z)