Given that driver mutations in cancers and other diseases only account for a small portion of all somatic mutations, we hypothesize that (1) the majority of somatic mutations are correlated with the regional features, such as epigenetic state and TF motifs, and the regional mutation rates can be predicted by these relevant features; in other words, somatic mutations in these regions are disease-independent and their occurrence is only related to the local environment rather than the disease state. Here, TF is linked to cancer.