Identification of genes that enhance cisplatin, gemcitabine, and paclitaxel cytotoxicity. HeLa cells grown in 384-well plates were transfected with individual siRNA pools targeting ∼2,400 human genes (3 siRNAs/gene). Four hours posttransfection, cells were treated with (y axis) or without (x axis) the following drugs: (A) cisplatin, 100 ng/ml; (B) gemcitabine, 7 nM; (C) paclitaxel, 1.2 nM. Cell growth was then measured at 72 h posttransfection using an Alamar blue assay and is expressed as the percentage of control viability (i.e., viability relative to wells transfected with an siRNA to luciferase). Diagonal red lines indicate twofold enhancement or suppression by drug treatment. Selected genes, which are labeled black, blue, or red, preferentially enhance cell killing by gemcitabine, paclitaxel, or cisplatin, respectively. (D) One-dimensional clustering of the overlap in consensus hits from cisplatin (Cis.), gemcitabine (Gem.), and paclitaxel (Tax.) siRNA screens. Consensus hits were defined as mean log2 (% viability plus drug/% viability with no drug) − 2 standard deviations in at least 2 of 3 screens for cisplatin and gemcitabine. For paclitaxel, consensus hits were defined as being as 1.7 standard deviations from the mean in two of two screens. Red color indicates the pool scored as a hit, and the gray color indicates that the pools were represented on the hit list.