Figure 1

Workflow for identifying significantly altered transcriptional and epigenetic regulations associated with the BRAF ^V600E driver mutation in melanoma. Matched expression A) and methylation profiles B) are built for BRAF ^V600E and BRAF ^WT samples. Expression and methylation data in the column highlighted in the same color are derived from the same sample. We used the Snowball approach (top) to identify significantly and differentially expressed genes. A schematic demonstration of the Snowball approach for the identification of BRAF ^V600E putative targets is shown in the top right panel. Gene expression profiles for multiple cancer samples are measured in two groups, BRAF ^V600E and BRAF ^WT. All genes (g1-g7) can be powerfully detected based on their co-expression profiles from the BRAF mutation and wild-type groups (for details see Materials and methods). The LIMMA method was applied to detect differential methylation loci between BRAF ^V600E and BRAF ^WT samples (bottom).