Abstract Motivation Population admixture is an important subject in population genetics. Inferring population demographic history with admixture under the so-called admixture network model from population genetic data is an established problem in genetics. Existing admixture network inference approaches work with single genetic polymorphisms. While these methods are usually very fast, they do not fully utilize the information [e.g. linkage disequilibrium (LD)] contained in population genetic data. Results In this article, we develop a new admixture network inference method called GTmix. Different from existing methods, GTmix works with local gene genealogies that can be inferred from population haplotypes. Local gene genealogies represent the evolutionary history of sampled haplotypes and contain the LD information. GTmix performs coalescent-based maximum likelihood inference of admixture networks with inferred local genealogies based on the well-known multispecies coalescent (MSC) model. GTmix utilizes various techniques to speed up the likelihood computation on the MSC model and the optimal network search. Our simulations show that GTmix can infer more accurate admixture networks with much smaller data than existing methods, even when these existing methods are given much larger data. GTmix is reasonably efficient and can analyze population genetic datasets of current interests. Availability and implementation The program GTmix is available for download at: https://github.com/yufengwudcs/GTmix. Supplementary information Supplementary data are available at Bioinformatics online.
more »
« less
Variational inference using approximate likelihood under the coalescent with recombination
Coalescent methods are proven and powerful tools for population genetics, phylogenetics, epidemiology, and other fields. A promising avenue for the analysis of large genomic alignments, which are increasingly common, is coalescent hidden Markov model (coalHMM) methods, but these methods have lacked general usability and flexibility. We introduce a novel method for automatically learning a coalHMM and inferring the posterior distributions of evolutionary parameters using black-box variational inference, with the transition rates between local genealogies derived empirically by simulation. This derivation enables our method to work directly with three or four taxa and through a divide-and-conquer approach with more taxa. Using a simulated data set resembling a human–chimp–gorilla scenario, we show that our method has comparable or better accuracy to previous coalHMM methods. Both species divergence times and population sizes were accurately inferred. The method also infers local genealogies, and we report on their accuracy. Furthermore, we discuss a potential direction for scaling the method to larger data sets through a divide-and-conquer approach. This accuracy means our method is useful now, and by deriving transition rates by simulation, it is flexible enough to enable future implementations of various population models.
more »
« less
- PAR ID:
- 10330466
- Date Published:
- Journal Name:
- Genome Research
- Volume:
- 31
- Issue:
- 11
- ISSN:
- 1088-9051
- Page Range / eLocation ID:
- 2107 to 2119
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
In this article, we advance divide-and-conquer strategies for solving the community detection problem in networks. We propose two algorithms that perform clustering on several small subgraphs and finally patch the results into a single clustering. The main advantage of these algorithms is that they significantly bring down the computational cost of traditional algorithms, including spectral clustering, semidefinite programs, modularity-based methods, likelihood-based methods, etc., without losing accuracy, and even improving accuracy at times. These algorithms are also, by nature, parallelizable. Since most traditional algorithms are accurate, and the corresponding optimization problems are much simpler in small problems, our divide-and-conquer methods provide an omnibus recipe for scaling traditional algorithms up to large networks. We prove the consistency of these algorithms under various subgraph selection procedures and perform extensive simulations and real-data analysis to understand the advantages of the divide-and-conquer approach in various settings.more » « less
-
Phylogenetic trees provide a framework for organizing evolutionary histories across the tree of life and aid downstream comparative analyses such as metagenomic identification. Methods that rely on single-marker genes such as 16S rRNA have produced trees of limited accuracy with hundreds of thousands of organisms, whereas methods that use genome-wide data are not scalable to large numbers of genomes. We introduce updating trees using divide-and-conquer (uDance), a method that enables updatable genome-wide inference using a divide-and-conquer strategy that refines different parts of the tree independently and can build off of existing trees, with high accuracy and scalability. With uDance, we infer a species tree of roughly 200,000 genomes using 387 marker genes, totaling 42.5 billion amino acid residues.more » « less
-
Abstract Neutrality tests such as Tajima’s D and Fay and Wu’s H are standard implements in the population genetics toolbox. One of their most common uses is to scan the genome for signals of natural selection. However, it is well understood that D and H are confounded by other evolutionary forces—in particular, population expansion—that may be unrelated to selection. Because they are not model-based, it is not clear how to deconfound these tests in a principled way. In this article, we derive new likelihood-based methods for detecting natural selection, which are robust to fluctuations in effective population size. At the core of our method is a novel probabilistic model of tree imbalance, which generalizes Kingman’s coalescent to allow certain aberrant tree topologies to arise more frequently than is expected under neutrality. We derive a frequency spectrum-based estimator that can be used in place of D, and also extend to the case where genealogies are first estimated. We benchmark our methods on real and simulated data, and provide an open source software implementation.more » « less
-
Schiffels, Stephan (Ed.)Movement of individuals between populations or demes is often restricted, especially between geographically isolated populations. The structured coalescent provides an elegant theoretical framework for describing how movement between populations shapes the genealogical history of sampled individuals and thereby structures genetic variation within and between populations. However, in the presence of recombination an individual may inherit different regions of their genome from different parents, resulting in a mosaic of genealogical histories across the genome, which can be represented by an Ancestral Recombination Graph (ARG). In this case, different genomic regions may have different ancestral histories and so different histories of movement between populations. Recombination therefore poses an additional challenge to phylogeographic methods that aim to reconstruct the movement of individuals from genealogies, although also a potential benefit in that different loci may contain additional information about movement. Here, we introduce the Structured Coalescent with Ancestral Recombination (SCAR) model, which builds on recent approximations to the structured coalescent by incorporating recombination into the ancestry of sampled individuals. The SCAR model allows us to infer how the migration history of sampled individuals varies across the genome from ARGs, and improves estimation of key population genetic parameters such as population sizes, recombination rates and migration rates. Using the SCAR model, we explore the potential and limitations of phylogeographic inference using full ARGs. We then apply the SCAR to lineages of the recombining fungus Aspergillus flavus sampled across the United States to explore patterns of recombination and migration across the genome.more » « less
An official website of the United States government

