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bioRxiv · 10.64898/2026.09.29.755279

methylTFR: Computational quantification of transcription factor activity from DNA methylation

Gunduz, I. B.·Nitsch, R.·Murugan, S. K.·Mueller, F.
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Abstract

DNA methylation modulates transcription factor (TF) binding, and plays an important role in regulating gene expression. We developed methylTFR, an R package for quantifying TF activity from DNA methylation across TF-binding sites, providing a low-dimensional and interpretable activity profile. Across 147 human immune cell methylomes, methylTFR identified cell-type-specific regulators, including CEBP and ETS family activity in myeloid cells. In CD4+ T cells, TF activity scores resolved the naive-to-memory trajectory and highlighted AP-1 factors as important memory regulators. We applied methylTFR to sparse single-cell methylome data, and we integrated derived activity scores with gene expression and accessibility into joint factor models yielding multimodal views of lineage regulators.

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Gunduz, I. B., Nitsch, R., Murugan, S. K., Mueller, F.. 2026-10-05. methylTFR: Computational quantification of transcription factor activity from DNA methylation. https://doi.org/10.64898/2026.09.29.755279

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