Construct background mutation rate (noise) based on the correlation of mutation frequency and expression levels or replication time. It has been shown that longer replication time and lower expression levels imply higher mutation rates among the genome (http://www.nature.com/nature/journal/v499/n7457/full/nature12213.html). Transcription-coupled DNA repair results in high expression levels and low mutation rate. So I would suggest to exclude the noise, then find out real driver mutations.
Idea No. 47