Genome-scale shRNA screen identifies mediators of resistance to prednisolone. (A) Reh cells were transduced with a genome-wide shRNA library and treated for 48 hours with vehicle or prednisolone at a concentration to yield a 75% inhibitory concentration (IC 75). After recovery from chemotherapy treatment, shRNA tags were isolated and quantified by deep sequencing. (B) Venn diagram illustrating the number of genes identified as hits through Bioinformatics for Next-Generation Sequencing (BiNGS), redundancy and fold-change (RFC), or both. (C) Diagrammatic representation of the MAPK pathway genes, with shRNA identified as depleted (blue) or enriched (red) in the shRNA screen. Genes identified by both BiNGS and RFC analyses are indicated by an asterisk. These data were integrated with genes identified to be upregulated by copy number gains (green) or hypomethylated at cytosine guanine dinucleotide promoter regions (purple) at relapse in primary pediatric ALL samples.