PUBLICATION
Gene co-expression network analysis in zebrafish reveals chemical class specific modules
- Authors
- Shankar, P., McClure, R.S., Waters, K.M., Tanguay, R.L.
- ID
- ZDB-PUB-210915-1
- Date
- 2021
- Source
- BMC Genomics 22: 658 (Journal)
- Registered Authors
- Shankar, Prarthana, Tanguay, Robyn L.
- Keywords
- Aryl hydrocarbon receptor, Development, Flame retardant chemicals, Gene co-expression, Network, Transcriptomics, Zebrafish
- Datasets
- GEO:GSE171944
- MeSH Terms
-
- Animals
- Base Sequence
- Embryo, Nonmammalian/metabolism
- Receptors, Aryl Hydrocarbon/genetics
- Receptors, Aryl Hydrocarbon/metabolism
- Transcriptome
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- PubMed
- 34517816 Full text @ BMC Genomics
Citation
Shankar, P., McClure, R.S., Waters, K.M., Tanguay, R.L. (2021) Gene co-expression network analysis in zebrafish reveals chemical class specific modules. BMC Genomics. 22:658.
Abstract
Background Zebrafish is a popular animal model used for high-throughput screening of chemical hazards, however, investigations of transcriptomic mechanisms of toxicity are still needed. Here, 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. Taking advantage of a compendium of phenotypically-anchored RNA sequencing data collected from 48-h post fertilization (hpf) zebrafish, we inferred a co-expression network that grouped genes based on their transcriptional response.
Results Genes responding to the FRCs and AHR2 Activators localized to distinct regions of the network, with FRCs inducing a broader response related to neurobehavior. AHR2 Activators centered in one region related to chemical stress responses. We also discovered several highly co-expressed genes in this module, including cyp1a, and we subsequently show that these genes are definitively within the AHR2 signaling pathway. Systematic removal of the two chemical types from the data, and analysis of network changes identified neurogenesis associated with FRCs, and regulation of vascular development associated with both chemical classes. We also identified highly connected genes responding specifically to each class that are potential biomarkers of exposure.
Conclusions Overall, we created the first zebrafish chemical-specific gene co-expression network illuminating how chemicals alter the transcriptome relative to each other. In addition to our conclusions regarding FRCs and AHR2 Activators, our network can be leveraged by other studies investigating chemical mechanisms of toxicity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping