Analysis of Co-Associated Transcription Factors via Ordered Adjacency Differences on Motif Distribution

Transcription factors (TFs) binding to specific DNA sequences or motifs, are elementary to the regulation of transcription. The gene is regulated by a combination of TFs in close proximity. Analysis of co-TFs is an important problem in understanding the mechanism of transcriptional regulation. Recently, ChIP-seq in mapping TF provides a large amount of experimental data to analyze co-TFs. Several studies show that if two TFs are co-associated, the relative distance between TFs exhibits a peak-like distribution. In order to analyze co-TFs, we develop a novel method to evaluate the associated situation between TFs. We design an adjacency score based on ordered differences, which can illustrate co-TF binding affinities for motif analysis. For all candidate motifs, we calculate corresponding adjacency scores, and then list descending-order motifs. From these lists, we can find co-TFs for candidate motifs. On ChIP-seq datasets, our method obtains best AUC results on five datasets, 0.9432 for NMYC, 0.9109 for KLF4, 0.9006 for ZFX, 0.8892 for ESRRB, 0.8920 for E2F1. Our method has great stability on large sample datasets. AUC results of our method on all datasets are above 0.8.