Raw sequencing data was uniformly processed using the bcbio-nextgen pipeline (v0.9.3). Briefly, sequencing reads were aligned to the human reference genome (hg19) using BWA62. Duplicated reads marked by Picard were removed. Indel regions were realigned using GATK63. Somatic mutations were called by four independent mutation callers: VarScan64, MuTect65, VarDict66, and FreeBayes67 using default parameters of the bcbio-nextgen pipeline. As the nature of our analyses requires high specificity in somatic mutation calling, we developed a random forest predictor, SMuRF68, trained on manually curated true somatic mutations to identify high confidence somatic mutation calls from the output of the four mutation callers. For each GC WGS sample, a set of high confidence consensus calls were obtained by running the random forest prediction algorithm.