Fig. 5

Direct versus indirect TF binding can be explained by the specific combination of co-binding TFs. a FOS co-binds with different set of TF partners when binding directly or indirectly. A subset of the regulatory module matrix that involves FOS binding are shown. Each cell in the heatmap represents the TF binding site count of a TF (row) in a module (column). dTF (in red) represents the direct binding sites. iTF (in green) represents the indirect binding sites. b RMD discovered specific combinations of TF indirect and direct binding. The heatmap shows the correlation between direct binding and indirect binding of 48 TFs based on their module participation. The top and left dendrograms were computed by applying hierarchical clustering on the correlation matrix with Pearson correlation distance and average linkage. Yellow boxes label combinations of TF indirect binding (yellow text) and direct binding (orange text). c Direct/indirect binding of some TFs can be predicted with high accuracy using the binding of co-binding TFs. A random forest classifier was trained to predict whether a TF binds directly or indirectly using the binding of the other TFs. Each point in the scatter plot is a TF. For a TF, a larger difference between the modules of direct binding and indirect binding corresponds to a higher the prediction accuracy by the random forest