Predicting the impact of sequence motifs on gene regulation using single-cell data

Autor: Jacob Hepkema, Nicholas Keone Lee, Benjamin J. Stewart, Siwat Ruangroengkulrith, Varodom Charoensawan, Menna R. Clatworthy, Martin Hemberg
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Genome Biology, Vol 24, Iss 1, Pp 1-22 (2023)
Druh dokumentu: article
ISSN: 1474-760X
DOI: 10.1186/s13059-023-03021-9
Popis: Abstract The binding of transcription factors at proximal promoters and distal enhancers is central to gene regulation. Identifying regulatory motifs and quantifying their impact on expression remains challenging. Using a convolutional neural network trained on single-cell data, we infer putative regulatory motifs and cell type-specific importance. Our model, scover, explains 29% of the variance in gene expression in multiple mouse tissues. Applying scover to distal enhancers identified using scATAC-seq from the developing human brain, we identify cell type-specific motif activities in distal enhancers. Scover can identify regulatory motifs and their importance from single-cell data where all parameters and outputs are easily interpretable.
Databáze: Directory of Open Access Journals