five for response dichotomization, Sadly, omic profiles and corresponding clinical responses will not be accessible for the other compounds tested in vitro. For these, we investigated regardless of whether the in vitro pre dictive signature was present in 536 breast TCGA tumors and consistent with all the signature observed in cell lines. Right here, we selleck chemicals restricted our analyses to these data varieties which are on the market within the TCGA dataset. Especially, we developed response predictors for the breast cancer cell line panel employing profiles for expression, copy quantity, and promoter methylation for 51 compounds for which predictive energy was high, We applied these signatures selleckchem to a set of 369 luminal, 95 basal, eight claudin low, and 58 ERBB2 amplified samples in the TCGA project. We applied profiles of expression, copy number and promoter methy lation in our analyses.
More file 5 shows that the transcriptional subtype specificities measured for these compounds in the cell lines have been concordant using the subtype of TCGA samples predicted to re spond. Figure S5 in Added file three shows the pre dicted probability of response to 4 compounds with test AUC 0. 7 for TCGA tumor samples ordered ac cording to increasing probability. Importantly, genes in these signatures that had been coordinately regulated inside the set of cell lines have been also coordinately regulated in the tumor samples, This panel of 51 compounds represented most important therapeutic target classes, re ceptor tyrosine kinase, anti mitotic, DNA damage, cell cycle, proteasome, anti metabolite, TP53, mitogen activated protein kinase, and estrogen antagon ist, Eighteen of those compounds have been approved by the US Food and Drug Administration, such as 5 for breast cancer.