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CycleVI: isolating cell cycle variation with an interpretable deep generative model
Vrije Univ Amsterdam, Syst Biol Lab, AIMMS A LIFE, Amsterdam, Netherlands.;European Mol Biol Lab, European Bioinformat Inst EMBL EBI, Hinxton, England..ORCID iD: 0009-0001-0009-5404
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0003-0556-2531
Vrije Univ Amsterdam, Syst Biol Lab, AIMMS A LIFE, Amsterdam, Netherlands..
2026 (English)In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 42, no 6, article id btag372Article in journal (Refereed) Published
Abstract [en]

Motivation Cell cycle progression is a dominant source of variation in single-cell RNA sequencing (scRNA-seq) data, often obscuring other transcriptional signals of interest. Several methods have been developed to infer continuous cell cycle phase from transcriptomic data, but their estimates tend to be unstable when proliferation is intertwined with other biological processes or technical sources of heterogeneity.Results We present CycleVI, a deep generative model that disentangles cell cycle-driven variation from other signals in scRNA-seq data using a partitioned latent representation with a dedicated circular subspace. CycleVI accurately infers a continuous cell cycle phase, validated against orthogonal protein-level measurements, and yields a residual latent space free of cell cycle artefacts. This disentangled representation helps resolve biological processes intertwined with the cell cycle, clarifying hematopoietic differentiation and preserving drug-response signals better than standard cell cycle regression. By isolating cell cycle-related variation rather than removing it, CycleVI provides a principled framework for analysing cellular heterogeneity in proliferating systems.Availability CycleVI is available at www.github.com/jeuken/CycleVI, or through the ' cyclevi' Python package.

Place, publisher, year, edition, pages
Oxford University Press, 2026. Vol. 42, no 6, article id btag372
National Category
Bioinformatics (Computational Biology) Bioinformatics and Computational Biology
Identifiers
URN: urn:nbn:se:uu:diva-594109DOI: 10.1093/bioinformatics/btag372ISI: 001804051000001PubMedID: 42334940Scopus ID: 2-s2.0-105042801213OAI: oai:DiVA.org:uu-594109DiVA, id: diva2:2086202
Available from: 2026-07-13 Created: 2026-07-13 Last updated: 2026-07-13Bibliographically approved

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