Systems Toxicology Approach for Testing Chemical Cardiotoxicity in Larval Zebrafish

• DOI: 10.1021/acs.chemrestox.0c00095
• Publication Date: 2020-07-08T11:18:20Z
• Authors: Roman Li; Anze Zupanic; Marja Talikka; Vincenzo Belcastro; Sumit Madan; Jens Dörpinghaus; Colette vom Berg; Justyna Szostak; Florian Martin; Manuel C. Peitsch; Julia Hoeng
• Keywords: Cardiotoxicity

Transcriptomic approaches can give insight into molecular mechanisms underlying chemical toxicity and are increasingly being used as part of toxicological assessments. To aid the interpretation transcriptomic data, we have developed a systems toxicology method that relies on computable biological network model. We created first model describing cardiotoxicity in zebrafish larvae—a valuable emerging species testing associated with drugs chemicals. The is based scientific literature represents hierarchical pathways lead from receptor activation to cardiac pathologies. test ability our approach detect cardiotoxic outcomes selected three publicly available data sets reported chemically induced heart pathologies larvae for five different Network-based analysis detected perturbations four out chemicals tested, two them using collected up 3 days before onset visible phenotype. Additionally, identified distinct were activated by results demonstrate proposed integrational be evaluating effects function and, together observed apical end points, provide comprehensive connecting events organ toxicity. freely may generate mechanistic hypotheses quantifiable perturbation values any data.