Evidence map›Paper›PMID 42837403›Full record

ArticlePLoS genetics2026

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

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

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Article in PLoS genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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7 authors.

Prateek AnandDepartment of Computer Science, University of California, Los Angeles, Los Angeles, California, United States of America.ORCID https://orcid.org/0009-0004-8455-1308
Anji LiuDepartment of Computer Science, National University of Singapore, Singapore, Singapore.
Meihua DangDepartment of Computer Science, Stanford University, Stanford, California, United States of America.ORCID https://orcid.org/0000-0001-8241-1943
Boyang FuDepartment of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, United States of America.
Xinzhu WeiDepartment of Computational Biology, Cornell University, Ithaca, New York, United States of America.ORCID https://orcid.org/0000-0001-8184-7016
Guy Van den BroeckDepartment of Computer Science, University of California, Los Angeles, Los Angeles, California, United States of America.
Sriram SankararamanDepartment of Computer Science, University of California, Los Angeles, Los Angeles, California, United States of America.ORCID https://orcid.org/0000-0003-1586-9641

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Genetics, PopulationGenetic VariationModels, GeneticAlgorithmsGenerative Artificial IntelligenceGenotypeHidden Markov ModelsHumansLinkage DisequilibriumMarkov ChainsPolymorphism, Single Nucleotide

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.