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RNAi–Based Functional Profiling of Loci from Blood Lipid Genome-Wide Association Studies Identifies Genes with Cholesterol-Regulatory Function

Figure 2

Multiparametric analysis and clustering of functional effector genes.

(A) Functional consequences upon knockdown of each candidate gene (using 3–5 different siRNAs/gene) were quantified from microscopic images with regard to seven phenotypic parameters: total cellular LDL-signal; LDL concentration and number of cellular structures; total free cholesterol (FC) signal; and FC concentration, area and number of cellular structures. Shown are heatmaps for 37 out of 55 most pronounced functional effector genes that according to parameter “total cellular intensity” (“total”) of the two strongest effector siRNAs/gene were clustered into five distinct functional groups (B–F) (see Figure S2 and Table S4 for comprehensive datasets). Phenotypes (red, increasing; blue, decreasing) meeting statistical criteria as described in Materials and Methods are framed in orange.

Figure 2