Computational prediction of drug response in short QT syndrome type 1 based on measurements of compound effect in stem cell-derived cardiomyocytes
Fig 1
Illustration of the computational pipeline.
1) Biomarkers from the cardiac AP are taken from hiPSC-CMs under drug testing. 2) These biomarkers from dose escalation studies are inverted into an SQT1 model of the AP of hiPSC-CMs. Inversion into a matched model provides determination of drug effects on specific channels [23]. 3) The drug effects determined in 2 are inserted into a model of adult CMs with the same SQT1 mutation to give a prediction of drug effect in mature CMs [22]. 4) The adult CM model is converted into pseudo-ECG waveforms for prediction of QT segment changes in SQT1 patients under the estimated effect of the drug.