PUBLICATION
pyHeart4Fish: Chamber-specific heart phenotype quantification of zebrafish in high-content screens
- Authors
- Vedder, V.L., Reinberger, T., Haider, S.M.I., Eichelmann, L., Odenthal, N., Abdelilah-Seyfried, S., Aherrahrou, Z., Breuer, M., Erdmann, J.
- ID
- ZDB-PUB-230429-76
- Date
- 2023
- Source
- Frontiers in cell and developmental biology 11: 11438521143852 (Journal)
- Registered Authors
- Abdelilah-Seyfried, Salim, Breuer, Maximilian, Vedder, Viviana
- Keywords
- Zebrafish, cardiovascular disease, development, drug effects, drug screen, heart, pyHeart4Fish, python GUI application
- MeSH Terms
- none
- PubMed
- 37113769 Full text @ Front Cell Dev Biol
Citation
Vedder, V.L., Reinberger, T., Haider, S.M.I., Eichelmann, L., Odenthal, N., Abdelilah-Seyfried, S., Aherrahrou, Z., Breuer, M., Erdmann, J. (2023) pyHeart4Fish: Chamber-specific heart phenotype quantification of zebrafish in high-content screens. Frontiers in cell and developmental biology. 11:11438521143852.
Abstract
Cardiovascular diseases (CVDs) are the leading cause of death. Of CVDs, congenital heart diseases are the most common congenital defects, with a prevalence of 1 in 100 live births. Despite the widespread knowledge that prenatal and postnatal drug exposure can lead to congenital abnormalities, the developmental toxicity of many FDA-approved drugs is rarely investigated. Therefore, to improve our understanding of drug side effects, we performed a high-content drug screen of 1,280 compounds using zebrafish as a model for cardiovascular analyses. Zebrafish are a well-established model for CVDs and developmental toxicity. However, flexible open-access tools to quantify cardiac phenotypes are lacking. Here, we provide pyHeart4Fish, a novel Python-based, platform-independent tool with a graphical user interface for automated quantification of cardiac chamber-specific parameters, such as heart rate (HR), contractility, arrhythmia score, and conduction score. In our study, about 10.5% of the tested drugs significantly affected HR at a concentration of 20 µM in zebrafish embryos at 2 days post-fertilization. Further, we provide insights into the effects of 13 compounds on the developing embryo, including the teratogenic effects of the steroid pregnenolone. In addition, analysis with pyHeart4Fish revealed multiple contractility defects induced by seven compounds. We also found implications for arrhythmias, such as atrioventricular block caused by chloropyramine HCl, as well as (R)-duloxetine HCl-induced atrial flutter. Taken together, our study presents a novel open-access tool for heart analysis and new data on potentially cardiotoxic compounds.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping