Fig. 5

Therapeutics targeting the marginal factor PIK3CA + HMCN1 to induce a specific RNA expression signature. a The strength of the signature (i.e., the magnitude of the gene expression change), the reproducibility of the signature, and the connectivity score of the candidate agents were assessed by determining the differential genetic signature caused by LRP1B mutation with or without PIK3CA + HMCN1 comutation in the stomach cancer cell line AGS. The x-axis denotes the replicate correlation coefficient, which represents how consistent the replicates were in a given experiment. The y-axis denotes the signature strength, which represents the magnitude of the gene expression change elicited by the candidate compounds. The z-axis denotes the connectivity score, which demonstrates the association between the mutation combination-induced RNA signature and the small compound-induced RNA signature. A positive score represents a scenario in which the drug induced a similar signature to the mutational panel; a negative score represents a scenario in which the drug induced a signature that was opposite of the mutational panel. b The primary chosen drugs may specifically repress the adverse RNA signature and satisfy the CMap default standards for determining strong and reproducible drugs. c The transcriptional activity scores (TASs) and connectivity scores identified a wide variety of cancer cell lines, including the gastric cancer cell line AGS, that were related to and affected by treatment with the CMap-selected molecule geldanamycin