SMORE: joint dimension reduction and cell population discovery on single-cell methylome data
- 1The University of Texas Health Science Center at Houston
Abstract
Single-cell DNA methylation profiling technology captures novel epigenetic data modality but are challenging to analyze because of their heterogeneity, high dimensionality, and ultra-sparsity. Here we present SMORE (Single-cell MethylOme Reduction and Embedding), a computational method for joint dimensionality reduction and cell population discovery dedicated to single-cell DNA methylation data. SMORE operates on a Bayesian framework that converts methylation proportions into ordered methylation states and jointly infers a low-dimensional representation, cell populations and their number. By using low-rank latent Gaussian factorization and adopting a mixture-of-finite-mixtures prior on latent cell scores, SMORE infers cell assignments without requiring a prespecified cluster number, and propagates uncertainty from methylation measurements to cell assignments. Across simulations spanning varying sample sizes, population imbalance, signal strengths and model misspecification, SMORE accurately recovered latent population structure and outperformed existing methods. Applied to human single-cell methylation datasets from lung, peripheral blood and primary motor cortex, SMORE recovered biologically supported cell population structures. SMORE provides an uncertainty-aware framework for dimension reduction and population discovery for single-cell methylomes.
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BibTeX
@misc{deng2026smore,
title = {{SMORE: joint dimension reduction and cell population discovery on single-cell methylome data}},
author = {J. Deng and Z. Wang and W. Tang and G. Hu and H. Feng},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.14.751514},
url = {https://www.biorxiv.org/content/10.64898/2026.09.14.751514v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - SMORE: joint dimension reduction and cell population discovery on single-cell methylome data
AU - J. Deng
AU - Z. Wang
AU - W. Tang
AU - G. Hu
AU - H. Feng
PY - 2026
DA - 2026/09/14
PB - bioRxiv
DO - 10.64898/2026.09.14.751514
UR - https://www.biorxiv.org/content/10.64898/2026.09.14.751514v1
AB - Single-cell DNA methylation profiling technology captures novel epigenetic data modality but are challenging to analyze because of their heterogeneity, high dimensionality, and ultra-sparsity. Here we present SMORE (Single-cell MethylOme Reduction and Embedding), a computational method for joint dimensionality reduction and cell population discovery dedicated to single-cell DNA methylation data. SMORE operates on a Bayesian framework that converts methylation proportions into ordered methylation states and jointly infers a low-dimensional representation, cell populations and their number. By using low-rank latent Gaussian factorization and adopting a mixture-of-finite-mixtures prior on latent cell scores, SMORE infers cell assignments without requiring a prespecified cluster number, and propagates uncertainty from methylation measurements to cell assignments. Across simulations spanning varying sample sizes, population imbalance, signal strengths and model misspecification, SMORE accurately recovered latent population structure and outperformed existing methods. Applied to human single-cell methylation datasets from lung, peripheral blood and primary motor cortex, SMORE recovered biologically supported cell population structures. SMORE provides an uncertainty-aware framework for dimension reduction and population discovery for single-cell methylomes.
ER -