PNNL

Abstract

Zebrafish are a popular model for high-throughput screening of chemical hazards, however, investigations of transcriptomic mechanisms of toxicity are needed. Our goal was to identify genes and biological pathways that Aryl Hydrocarbon Receptor 2 (AHR2) Activators and flame retardant chemicals (FRCs) alter in developing zebrafish. Using a compendium of 48-hpf RNA-sequencing data, we inferred a co-expression network that grouped genes based on transcriptional response. Genes responding to FRCs and AHR2 Activators localized to distinct regions, with FRCs inducing a broad neurobehavioral response. AHR2 Activators altered a cluster of chemical stress response genes ,including cyp1a, subsequently found to be within the AHR2 signaling pathway. Systematic removal of the two toxicant types from the data and analysis of network changes identified neurogenesis associated with FRCs, and regulation of vascular development associated with both classes. Here, we created the first zebrafish chemical-specific gene co-expression network illuminating how chemicals alter the transcriptomic map relative to each other. In addition to our conclusions regarding FRCs and AHR2 toxicants our network can also be leveraged by other studies investigating chemical mechanisms of toxicity.