Drug Combination Signatures for Prediction and Mitigation of Toxicity

Generation and extensive characterization of a gender-balanced, racially/ethnically diverse library of iPSCs from forty clinically healthy human individuals who range in age from 22-61. Specifically, here we provide mRNAseq data of duplicate samples of one clone from each of these forty iPSC lines. Overall design: bulk mRNA-seq data files for 80 human iPSC samples at the control condition generated by random-primed mRNA-sequencing method 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 recruited and pre-screend healthy individuals to be included in our study. Ninty six male and female individuals that satisfied the initial pre-screening for the study and their sex, age, race/ethnicity recorded through an enrollment questionnaire were consented. Eighty five underwent a formal and thorough medical health screening. The evlaution involved assessment of all inclusion and exclusion criteria, a full medical history, measurement of weight, height, waist and hip circumference, heart rate, blood pressure, respiratory rate, and oxygen saturation, a physical exam and an electrocardiograph (ECG). Blood was drawn for analysis of clinical relevant parameters. A pregnancy test was included for female participants. All blood draws and pregnancy tests were sent to a certified clinical laboratory for clinical analysis. Of the 85 subjects that were screened 42 (48.3%) were deemed eligible for final inclusion. Of these 42, one declined to undergo skin biopsy and/or venesection and one suject didn't show up for the scheduled biopsy, leaving 40 clinically healthy subjects on which a skin biopsy and venesection was performed. Fibroblast lines were established from the skin biopsies. Induced pluripotent cells (iPSC) were generated from the established fibroblast lines of these forty clinically healthy racially diverse male and female study participants who ranged in age from 22 and 61 years through reprogramming using either the mRNA or Sendai-virus methods. One clone from each of the forty iPSC 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. Specifically, mRNAseq was performed in duplicate samples of one clone from each of the 40 iPSC lines.