Drug Combination Signatures for Prediction and Mitigation of Toxicity.

Baseline transcriptomic signatures of cardiomyocytes differentiated from hiPSC lines generated from clinically well-characterized, diverse healthy human individuals. We provide mRNAseq data of various replicate samples of cardiomyocytes differentiated from 6 hiPSC lines. Overall design: The overall goal of the drug signatures for prediction and mitigation of toxicity study is to use genomic and proteomic high-throughput measurements as the basis for computational analysis that integrates network analyses with structural constraints and dynamical models in multiple cell types to identify signatures that predict toxicity induced by 55 FDA-approved chemotherapeutic drugs and potential mitigation of this toxicity. For this purpose, we have generated human induced pluripotent cell (hiPSC) lines from established fibroblast lines of forty clinically healthy racially diverse male and female study participants who ranged in age from 22 and 61 years. One clone from each of the forty hiPSC line was fully characterized for normal karyotype, short-tandem repeat matching to the original fibroblast line (authentication), pluripotency by select pluripotent marker expression via immunocytochemistry and by mRNAseq-based PluriTest analysis, and whole-genome sequencing. In order to establish hiPSC line-specific baseline (vehicle/control treatment) drug toxicity trasncriptomic signatures, cardiomyocytes were differentiated from 6 (3 male and 3 female) hiPSC lines using an established protocol, purified to 95% purity (SIRPA+CD90-) using a metabolic switch protocol, reseeded and treated for 48 hrs with DMSO (14.1 mM) before mRNAseq was performed on various replicate samples (biological/independent differentiations as well as technical/independent wells).