Accounting for long-range correlations in genome-wide simulations of large cohorts

English version

Autoři: Dominic Nelson ^aff001; Jerome Kelleher ^aff002; Aaron P. Ragsdale ^aff001; Claudia Moreau ^aff003; Gil McVean ^aff002; Simon Gravel ^aff001
Působiště autorů: McGill University and Genome Québec Innovation Centre, McGill University, Montréal, Québec, Canada ^aff001; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom ^aff002; Centre Intersectoriel en Santé Durable, Université du Québec à Chicoutimi, Saguenay, Québec, Canada ^aff003
Vyšlo v časopise: Accounting for long-range correlations in genome-wide simulations of large cohorts. PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008619
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008619

Souhrn

Coalescent simulations are widely used to examine the effects of evolution and demographic history on the genetic makeup of populations. Thanks to recent progress in algorithms and data structures, simulators such as the widely-used msprime now provide genome-wide simulations for millions of individuals. However, this software relies on classic coalescent theory and its assumptions that sample sizes are small and that the region being simulated is short. Here we show that coalescent simulations of long regions of the genome exhibit large biases in identity-by-descent (IBD), long-range linkage disequilibrium (LD), and ancestry patterns, particularly when the sample size is large. We present a Wright-Fisher extension to msprime, and show that it produces more realistic distributions of IBD, LD, and ancestry proportions, while also addressing more subtle biases of the coalescent. Further, these extensions are more computationally efficient than state-of-the-art coalescent simulations when simulating long regions, including whole-genome data. For shorter regions, efficiency can be maintained via a hybrid model which simulates the recent past under the Wright-Fisher model and uses coalescent simulations in the distant past.

Klíčová slova:

DNA recombination – Effective population size – Genetic polymorphism – Genome evolution – Linkage disequilibrium – Population genetics – Population size – Simulation and modeling

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