methylTFR: Computational quantification of transcription factor activity from DNA methylation

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.