Section: Mathematical & Computational Biology
Topic: Statistics, Biophysics and computational biology, Genetics/genomics

A new iterative framework for simulation-based population genetic inference with improved coverage properties of confidence intervals

Rousset, François1 orcid ; Leblois, Raphaël2 orcid; Estoup, Arnaud2 orcid; Marin, Jean-Michel3 orcid
1ISEM, Univ Montpellier, CNRS, IRD, 34095 Montpellier, France
2CBGP, INRAE, CIRAD, IRD, Institut Agro, Univ Montpellier, 34980 Montferrier-sur-Lez, France
3IMAG, Univ Montpellier, 34095 Montpellier, France

Corresponding author(s): Rousset, François (francois.rousset@umontpellier.fr)

10.24072/pcjournal.721 - Peer Community Journal, Volume 6 (2026), article no. e43

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Simulation-based methods such as approximate Bayesian computation (ABC) are widely used to infer the evolutionary history of populations from molecular genetic data. We describe and evaluate a new iterative method of statistical inference about model parameters, which revisits the idea of inferring a likelihood surface using simulation when the likelihood function cannot be evaluated. It is based on combining the random forest machine learning method, and multivariate Gaussian mixture (MGM) models, in an effective inference workflow, here used to fit models with up to 15 variable parameters. In addition to the traditional assessment of precision in terms of bias and mean square error, we also evaluate the coverage of confidence intervals. The method is compared with approximate Bayesian computation using random forests (ABC-RF), a non-iterative method sharing some technical features with the proposed approach, across scenarios of historical demographic inference from population genetic data. It is also compared to another iterative method, sequential neural likelihood estimation (SNLE). These comparisons highlight the importance of an iterative workflow for exploring the parameter space efficiently. For equivalent simulation effort of the data-generating process, the new summary-likelihood method provides intervals whose coverage is better controlled than the marginal coverage of intervals provided by ABC with random forests, and than generally reported for ABC methods. The iterative workflow can also yield greater improvements in estimator precision when larger datasets are used.

Published online:
DOI: 10.24072/pcjournal.721
Type: Research article
Classification:
Keywords: statistical inference; simulation-based inference; demographic history; polupation genetics

Rousset, François  1 ; Leblois, Raphaël  2 ; Estoup, Arnaud  2 ; Marin, Jean-Michel  3

1 ISEM, Univ Montpellier, CNRS, IRD, 34095 Montpellier, France
2 CBGP, INRAE, CIRAD, IRD, Institut Agro, Univ Montpellier, 34980 Montferrier-sur-Lez, France
3 IMAG, Univ Montpellier, 34095 Montpellier, France
License: CC-BY 4.0
Copyrights: The authors retain unrestricted copyrights and publishing rights
Rousset, F.; Leblois, R.; Estoup, A.; Marin, J.-M. A new iterative framework for simulation-based population genetic inference with improved coverage properties of confidence intervals. Peer Community Journal, Volume 6 (2026), article  no. e43. https://doi.org/10.24072/pcjournal.721
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PCI peer reviews and recommendation, and links to data, scripts, code and supplementary information: 10.24072/pci.mcb.100426

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The recommender in charge of the evaluation of the article and the reviewers declared that they have no conflict of interest (as defined in the code of conduct of PCI) with the authors or with the content of the article.

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