GPC: An expressive and tractable deep generative model for genetic variation data

Generative models play an important role in population genetics, being used to generate artificial genomes (AGs) that help benchmark methods, test evolutionary hypotheses, and construct reference panels for imputation while working around data-sharing restrictions. Existing generative models of genetic variation, however, struggle to faithfully express dependencies in the data while retaining tractability and preserving privacy. We introduce Genetic Probabilistic Circuits ( GPC ), a deep generative model for genetic variation data based on hidden Chow-Liu trees represented as probabilistic circuits. GPC generalizes traditional hidden Markov models by allowing arbitrary tree structures over latent variables, enabling it to capture long-range dependencies among SNPs. GPC is tractable, supporting exact computation of marginal and conditional probabilities that enables both AG generation and direct genotype imputation (avoiding the need for simulating AGs). We show that GPC generates AGs that accurately reproduce population structure and linkage disequilibrium patterns across a range of length scales. Compared to other deep generative approaches, GPC consistently improves imputation accuracy, with particularly strong gains for low-frequency variants and in populations that are not well-represented in public reference panels. Finally, we show that GPC better preserves privacy of the training data, thereby providing a practical framework for AG generation in settings with limited data access.

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Publication Details

Journal
PLoS Genetics
Published
2026-10-06
DOI
https://doi.org/10.1371/journal.pgen.1012321
Primary Topic
Genetic Associations and Epidemiology
Type
article
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article

GPC: An expressive and tractable deep generative model for genetic variation data

Xinzhu Wei, Guy Van den Broeck, Boyang Fu, Meihua Dang et al.
PLoS Genetics
Genetic Associations and Epidemiology
article

GPC: An expressive and tractable deep generative model for genetic variation data

Xinzhu Wei, Guy Van den Broeck, Boyang Fu, Meihua Dang, Sriram S Sankararaman, Anji Liu, Prateek Anand
article en

Abstract

Generative models play an important role in population genetics, being used to generate artificial genomes (AGs) that help benchmark methods, test evolutionary hypotheses, and construct reference panels for imputation while working around data-sharing restrictions. Existing generative models of genetic variation, however, struggle to faithfully express dependencies in the data while retaining tractability and preserving privacy. We introduce Genetic Probabilistic Circuits ( GPC ), a deep generative model for genetic variation data based on hidden Chow-Liu trees represented as probabilistic circuits. GPC generalizes traditional hidden Markov models by allowing arbitrary tree structures over latent variables, enabling it to capture long-range dependencies among SNPs. GPC is tractable, supporting exact computation of marginal and conditional probabilities that enables both AG generation and direct genotype imputation (avoiding the need for simulating AGs). We show that GPC generates AGs that accurately reproduce population structure and linkage disequilibrium patterns across a range of length scales. Compared to other deep generative approaches, GPC consistently improves imputation accuracy, with particularly strong gains for low-frequency variants and in populations that are not well-represented in public reference panels. Finally, we show that GPC better preserves privacy of the training data, thereby providing a practical framework for AG generation in settings with limited data access.

PLoS GeneticsVol. 22(10)
Harvard University (US), University of California, Los Angeles (US), National University of Singapore (SG), Cornell University (US), Stanford University (US)
Openalex Percentile: Top 13%
Genetic Associations and Epidemiology
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