ArticleNPJ systems biology and applications2018
Population-based mechanistic modeling allows for quantitative predictions of drug responses across cell types.
Article in NPJ systems biology and applications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 80 citations in OpenAlex.
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- Population Modeling Approach for Human Cardiac Arrhythmia Risk Prediction.Circulation. Arrhythmia and electrophysiology · 2026Article
- Large-scale synthetic data enable digital twins of human excitable cells.bioRxiv : the preprint server for biology · 2025Article
- Calcium Homeostatic Feedback Control Predicts Atrial Fibrillation Initiation, Remodeling, and Progression.JACC. Clinical electrophysiology · 2025Article
- Computational modelling for improved translation of cardiac inotropic and lusitropic drug effects from rats to humans.Journal of pharmacological and toxicological methods · 2025Article
- Creating cell-specific computational models of stem cell-derived cardiomyocytes using optical experiments.PLoS computational biology · 2024Article
- Advances in induced pluripotent stem cell-derived cardiac myocytes: technological breakthroughs, key discoveries and new applications.The Journal of physiology · 2024Review
- Creating cell-specific computational models of stem cell-derived cardiomyocytes using optical experiments.bioRxiv : the preprint server for biology · 2024Article
- Assessing drug safety by identifying the axis of arrhythmia in cardiomyocyte electrophysiology.eLife · 2023Article
- Crossing the Great Sex-Specific Divide in Cardiac Electrophysiology.JACC. Clinical electrophysiology · 2023Article
- Diversity of cells and signals in the cardiovascular system.The Journal of physiology · 2023Article
- Animal Disease Models and Patient-iPS-Cell-Derived In Vitro Disease Models for Cardiovascular Biology-How Close to Disease?Biology · 2023Review
- Emerging methods to model cardiac ion channel and myocyte electrophysiology.Biophysics reviews · 2023Review
- Building blocks of microphysiological system to model physiology and pathophysiology of human heart.Frontiers in physiology · 2023Review
- Predicting individual-specific cardiotoxicity responses induced by tyrosine kinase inhibitors.Frontiers in pharmacology · 2023Article
- Human induced pluripotent stem cell-derived cardiomyocytes as an electrophysiological model: Opportunities and challenges-The Hamburg perspective.Frontiers in physiology · 2023Review
- An in silico-in vitro pipeline for drug cardiotoxicity screening identifies ionic pro-arrhythmia mechanisms.British journal of pharmacology · 2022Article
- Understanding virtual patients efficiently and rigorously by combining machine learning with dynamical modelling.Journal of pharmacokinetics and pharmacodynamics · 2022Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Quantitative mismatches between human physiology and experimental models can be problematic for the development of effective therapeutics. When the effects of drugs on human adult cardiac electrophysiology are of interest, phenotypic differences with animal cells, and more recently stem cell-derived models, can present serious limitations. We addressed this issue through a combination of mechanistic mathematical modeling and statistical analyses. Physiological metrics were simulated in heterogeneous populations of models describing cardiac myocytes from adult ventricles and those derived from induced pluripotent stem cells (iPSC-CMs). These simulated measures were used to construct a cross-cell type regression model that predicts adult myocyte drug responses from iPSC-CM behaviors. We found that (1) quantitatively accurate predictions of responses to selective or non-selective ion channel blocking drugs could be generated based on iPSC-CM responses under multiple experimental conditions; (2) altering extracellular ion concentrations is an effective experimental perturbation for improving the model's predictive strength; (3) the method can be extended to predict and contrast drug responses in diseased as well as healthy cells, indicating a broader application of the concept. This cross-cell type model can be of great value in drug development, and the approach, which can be applied to other fields, represents an important strategy for overcoming experimental model limitations.
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.