The TRAC Calculator is an open-source, web-based tool for assessing torsades de pointes (TdP) proarrhythmic risk of small molecule compounds. It uses electrophysiological response predictors measured in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as part of the Comprehensive In Vitro Proarrhythmia Assay (CiPA) paradigm.
This tool implements a logistic regression–based model trained on large, multisite datasets, providing researchers and regulators with reproducible, human-relevant risk predictions.
You can directly run the program in this package by visiting the live TRAC Calculator webpage and follow the instructions on the page.
- Three validated predictors:
- Arrhythmia-like event occurrence (categorical)
- Maximum repolarization change (ms) observed at any concentration
- Repolarization change (ms) at expected Cmax
- Two input modes:
- Direct predictor input
- Cmax interpolation with concentration–response curve fitting (Hill curve with Hill coefficient fixed at 1)
- Program outputs:
- Predicted probability of Low risk vs High or Intermediate risk
- Bar chart of risk probabilities
- Hill-fit concentration–response plot with Cmax overlay
- Context of Use (COU) and Limitations documented with links to key references.
Developer: Marshall Ma ([email protected], [email protected])
Advisor(s): TK Feaster ([email protected]), Ksenia Blinova ([email protected])
The TRAC Calculator is a browser-based app (no installation required). Clone or download this repository and open index.html in a web browser.
- Review the Context of Use and Limitations of Use.
- Enter predictor values in the Predictor Inputs panel.
- Predictor ranges are shown in the input fields upon startup.
- Optionally, use the Cmax Interpolation panel to fit a concentration–FPDc curve and automatically generate predictors.
- Click Calculate to view the outputs.
- Logistic regression model results are displayed under Program Outputs.
- Graphical plots update dynamically:
- Risk probability bar chart
- Hill-fit concentration–response curve (if Cmax interpolation is used)
- Blinova K. et al. (2018). International Multisite Study of Human iPSC-CMs for Drug Proarrhythmic Potential Assessment. Cell Reports, 24(13): 3582–3592. doi:10.1016/j.celrep.2018.08.079
- Patel D. et al. (2019). Assessment of Proarrhythmic Potential of Drugs in Optogenetically Paced hiPSC-CMs. Toxicological Sciences, 170(1): 167–179. doi:10.1093/toxsci/kfz076
- Gintant G. et al. (2020). Repolarization studies using human stem cell-derived cardiomyocytes: Validation studies and best practice recommendations. Regul Toxicol Pharmacol, 117: 104756. doi:10.1016/j.yrtph.2020.104756
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This work is licensed under a Creative Commons Attribution 4.0 International License.
CC BY 4.0
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