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Title: Gene co-expression network analysis in zebrafish reveals chemical class specific modules

Journal Article · · BMC Genomics
 [1];  [2]; ORCiD logo [3];  [1]
  1. Oregon State Univ., Corvallis, OR (United States)
  2. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  3. Oregon State Univ., Corvallis, OR (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

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. 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. 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.

Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC05-76RL01830
OSTI ID:
1827256
Report Number(s):
PNNL-SA--160902
Journal Information:
BMC Genomics, Journal Name: BMC Genomics Journal Issue: 1 Vol. 22; ISSN 1471-2164
Publisher:
SpringerCopyright Statement
Country of Publication:
United States
Language:
English

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