Cornejo-Páramo, Paola and Zhang, Xuan and Louis, Lithin and Li, Zelun and Yang, Yihua and Wong, Emily S. (2025) Motif-based models accurately predict cell type-specific distal regulatory elements. Nature Communications, 16 (1). ISSN 2041-1723
Full text not available from this repository.Abstract
Abstract
Deciphering how DNA sequence specifies cell-type-specific regulatory activity is a central challenge in gene regulation. We present Bag-of-Motifs (BOM), a computational framework that represents distal cis-regulatory elements as unordered counts of transcription factor (TF) motifs. This minimalist representation, combined with gradient-boosted trees, enables the accurate prediction of cell-type-specific enhancers across mouse, human, zebrafish, and Arabidopsis datasets. Despite its simplicity, BOM outperforms more complex deep-learning models while using fewer parameters. We validate BOM’s predictions experimentally by constructing synthetic enhancers from the most predictive motifs, demonstrating that these motif sets drive cell-type-specific expression. By providing direct interpretability and broad applicability, BOM reveals a highly predictive sequence code at distal regulatory regions and offers a scalable framework for dissecting cis-regulatory grammar across diverse species and conditions.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 20 Dec 2025 04:05 |
| Last Modified: | 20 Dec 2025 04:05 |
| URI: | http://eprints.victorchang.edu.au/id/eprint/1778 |
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