SAKE (Single-cell RNA-Seq Analysis and Klustering Evaluation) Identifies Markers of Resistance to Targeted BRAF Inhibitors in Melanoma Cell Populations [Bulk RNA-Seq]

The goal of this study is to apply the SAKE algorithms to identify drug-resistant cellular populations as human melanoma cells respond to targeted BRAF inhibitors. Single-cell RNA-Seq data from both the SMART-seq/Fluidigm and 10x Genomics platforms were analyzed to dissect this problem at multiple scales. Data from both platforms indicate that BRAF inhibitor resistant cells can emerge from rare populations already present before drug application, with SAKE identifying both novel and known markers of resistance Two Melanoma cell lines were treated with BRAF inhibitor for 6 weeks to derived a parental and resistant cell states. Bulk and single-cell RNA-Seq were generated using Illumina Hiseq 2000 to study cell response after drug treatment.