Virtual ChIP-seq: predicting transcription factor binding by learning from the transcriptome

Existing methods for computational prediction of transcription factor (TF) binding sites evaluate genomic regions with similarity to known TF sequence preferences. Most TF binding sites, however, do not resemble known TF sequence motifs, and many TFs are not sequence-specific. We developed Virtual ChIP-seq, which predicts binding of individual TFs in new cell types, integrating learned associations with gene expression and binding, TF binding sites from other cell types, and chromatin accessibility data in the new cell type. This approach outperforms methods that predict TF binding solely based on sequence preference, predicting binding for 36 TFs (MCC>0.3).