Phenotypically anchored mRNA and miRNA expression profiling in zebrafish reveals flame retardant chemical toxicity networks
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA714931 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13979100.fastq.gz | Fastqsanger.gz | |||
| SRR13979101.fastq.gz | Fastqsanger.gz | |||
| SRR13979102.fastq.gz | Fastqsanger.gz | |||
| SRR13979103.fastq.gz | Fastqsanger.gz | |||
| SRR13979104.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: Assess transcriptomic changes in response to phenotypically-anchored retene concentrations. By combining data from all concentrations, we inferred a gene co-expression network highlighting key transcripts and modules important to toxicity response to retene.
2022-05-21 | GSE203258 | GEO
Project description:Purpose: The goals of this study are to examine mRNA and miR networks on exposures to flame retardant chemicals (FRCs), an ubiquitous group of chemicals in the environment Methods: Four biological replicates were created by pooling eight embryos per replicate from individual wells which were placed into an Eppendorf Safelock Tube and excess solution removed. 0.5 mM zirconium oxide beads were added along with 500 µL of RNAzol (Molecular Research Center, Inc.) and the tubes were immediately placed into a bullet blender (Next Advance), using settings recommended by the manufacturer. The RNA was purified using the Direct-zol MiniPrep kit (Zymo Research), including an optional DNase-1 digestion treatment for 15 minutes. RNA integrity (RIN) was assessed using an Agilent Bioanalyzer (Santa Clara, CA), and RNA samples with RIN values >8 were processed for library preparation and sequencing at the Oregon State University Center for Genome Research and Biocomputing. Total RNA was used as input for both mRNA and miRNA sequencing. For mRNA sequencing, mRNA was poly A selected, libraries were prepared with the PrepX™ mRNA and Illumina sequencing workflow (Wafergen Biosystems). For miRNA seq, the Illumina TruSeq Small RNA library kit was used to generate small RNA libraries from total RNA. For sequencing, an Illumina HiSeq 3000 sequencer (Illumina, San Diego) was used for mRNA and small RNA single-end sequencing at 100 and 50 base pairs, respectively. Bioinformatics analysis of sequencing data was performed on an R platform. Briefly, reads were evaluated by FastQC v0.11.3 to detect major sequencing problems, and then trimmed for quality control with Skewer v0.2.2 . RNA-seq alignment and quantification proceeded with Bowtie2 v2.2.3 being used to build HISAT2 (Kim et al., 2013) genome index files from the Genome Reference Consortium Zebrafish Build 10 (GRCz10) genome. For miR identification and quantification, a combination of miRDeep2 v2.0.0.8, miRBase release 22 and Bowtie v1.2.1.1 were used. Differential expression between experimental and control samples was determined with functions from the Bioconductor package, edgeR; mRNAs with a log2 fold change ≥1.5 and Benjamini-Hochberg (BH) adjusted p ≤ 0.05 were considered differentially expressed while an adjusted p ≤ 0.05 was applied to miRs without any fold change cutoffs. Heatmap clustering of differentially expressed genes were generated in R based on their log2 fold changes using the ggplot2 package. Results: We found widespread disruption of mRNA and miR expression. Neurodevelopment was a key disrupted biological process across multiple FRCs and was corroborated by behavioral deficits. Several mRNAs (eg: osbpl2a) and miRs (eg- mir-125b-5p), showed differential expression common to multiple FRCs (10 and 7 respectively). These common miRs were also predicted to regulate a network of differentially expressed genes with diverse functions, including apoptosis, neurodevelopment, lipid regulation and inflammation. Commonly disrupted transcription factors (TFs) such as RXR, RAR and VDR were predicted to regulate a wide network of differentially expressed mRNAs across a majority of the FRCs. Many of the differential mRNA-TF and mRNA-miR pairs were predicted to play important roles in development as well as cancer signaling. Specific comparisons between TBBPA and its derivative TBBPA-DBPE showed contrasting gene expression patterns that corroborated with their phenotypic profiles. The newer generation FRCs such as IPP and TCEP produced distinct gene expression changes compared to the legacy FRC BDE-47. Conclusions: Our study is the first to establish a mRNA-miR-TF regulatory network across a large group of structurally diverse FRCs and diverse phenotypic responses. The purpose was to discover common and unique biological targets that will help us understand mechanisms of action for these important chemicals.
2021-03-17 | GSE169013 | GEO
Project description:The ubiquitous use of flame retardant chemicals (FRCs) in the manufacture of many consumer products leads to inevitable environmental releases and human exposures. Studying toxic effects of FRCs as a group is challenging since they widely differ in physicochemical properties. We previously used zebrafish as a model to screen 61 representative FRCs and showed that many induced behavioral and teratogenic effects, with aryl phosphates identified as the most active. In this study, we selected 10 FRCs belonging to diverse physicochemical classes and zebrafish toxicity profiles to identify the gene expression responses following exposures. For each FRC, we executed paired mRNA-micro-RNA (miR) sequencing, which enabled us to study mRNA expression patterns and investigate the role of miRs as posttranscriptional regulators of gene expression. We found widespread disruption of mRNA and miR expression across several FRCs. Neurodevelopment was a key disrupted biological process across multiple FRCs and was corroborated by behavioral deficits. Several mRNAs (e.g., osbpl2a) and miRs (e.g., mir-125b-5p), showed differential expression common to multiple FRCs (10 and 7 respectively). These common miRs were also predicted to regulate a network of differentially expressed genes with diverse functions, including apoptosis, neurodevelopment, lipid regulation and inflammation. Commonly disrupted transcription factors (TFs) such as retinoic acid receptor, retinoid X receptor, and vitamin D regulator were predicted to regulate a wide network of differentially expressed mRNAs across a majority of the FRCs. Many of the differential mRNA-TF and mRNA-miR pairs were predicted to play important roles in development as well as cancer signaling. Specific comparisons between TBBPA and its derivative TBBPA-DBPE showed contrasting gene expression patterns that corroborated with their phenotypic profiles. The newer generation FRCs such as IPP and TCEP produced distinct gene expression changes compared to the legacy FRC BDE-47. Our study is the first to establish a mRNA-miR-TF regulatory network across a large group of structurally diverse FRCs and diverse phenotypic responses. The purpose was to discover common and unique biological targets that will help us understand mechanisms of action for these important chemicals and establish this approach as an important tool for better understanding toxic effects of environmental contaminants.
| S-EPMC8063052 | biostudies-literature
Project description:Concentration-response gene expression analysis in zebrafish reveals phenotypically-anchored transcriptional responses to retene
| PRJNA839281 | ENA
Project description:Daphnia magna is a bio-indicator organism accepted by several international water quality regulatory agencies. Current approaches for assessment of water quality rely on acute and chronic toxicity that provide no insight into the cause of toxicity. Recently, molecular approaches, such as genome wide gene expression responses, are enabling an alternative mechanism based approach to toxicity assessment. While these genomic methods are providing important mechanistic insight into toxicity, statistically robust prediction systems that allow the identification of chemical contaminants from the molecular response to exposure are needed. Here we apply advanced machine learning approaches to develop predictive models of contaminant exposure using a D. magna gene expression dataset for 36 chemical exposures. We demonstrate here that we can discriminate between chemicals belonging to different chemical classes including endocrine disruptors, metals and industrial chemicals based on gene expression. We also show that predictive models based on indices of whole pathway transcriptional activity can achieve comparable results while facilitating biological interpretability. D. magna were exposed to 36 Chemicals and 5 control series in quadruplicate.
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Project description:Thorium (232Th), an actinoide element, is among the most common and naturally occurring radioactive materials distributed in our environment. Thorium has been used as a radiographic contrast agent (thorotrast) from 1930 to 1955, and many studies on its effects to the human body have been reported. Once thorium is injected in the body, the risk of cancer is increased by the direct bombardment from alpha-particle with high linear energy transfer during decay of Thorium. However, these many reports focus on the irradiation damage by long-term exposure of thorium. The acute toxicity of thorium is greater risk from the chemical toxicity than from the radiological toxicity. Here, we evaluated the effect of thorium from the stand point of chemical toxicity using yeast DNA microarray. In this experiment, genes that contribute to “C-compound and carbohydrate metabolism”, “energy”, and “cell rescue, defense and virulence” were significantly induced. These genes were classified into oxidative stress, glycogen and trehalose metabolism, sugar transport, and cell wall damage. On the contrary, only one gene related to DNA damage was detected. These results indicate that thorium causes the damage of cell wall and induces the oxidative stress. In order to overcome oxidative stress, yeast cells promote the glycogen and trehalose metabolisms and shift to anaerobic fermentation. Keywords: stress response
2007-11-01 | GSE9463 | GEO
Project description:Daphnia magna is a bio-indicator organism accepted by several international water quality regulatory agencies. Current approaches for assessment of water quality rely on acute and chronic toxicity that provide no insight into the cause of toxicity. Recently, molecular approaches, such as genome wide gene expression responses, are enabling an alternative mechanism based approach to toxicity assessment. While these genomic methods are providing important mechanistic insight into toxicity, statistically robust prediction systems that allow the identification of chemical contaminants from the molecular response to exposure are needed. Here we apply advanced machine learning approaches to develop predictive models of contaminant exposure using a D. magna gene expression dataset for 36 chemical exposures. We demonstrate here that we can discriminate between chemicals belonging to different chemical classes including endocrine disruptors, metals and industrial chemicals based on gene expression. We also show that predictive models based on indices of whole pathway transcriptional activity can achieve comparable results while facilitating biological interpretability.
2013-01-17 | GSE43564 | GEO
Project description:Although alternative Flame Retardant (FR) chemicals are expected to be safer than the legacy FRs they replace, their risks to human health and the environment are often poorly characterized. This study used a small volume, fish embryo system to reveal potential mechanisms of action and diagnostic exposure patterns for TBPH (bis (2-ethylhexyl)-tetrabromophthalate), a component of several widely-used commercial products. By design, environmentally-high exposures of TBPH were applied to sensitive early life stages of an ecologically important test species, Fundulus heteroclitus (Atlantic killifish), with a well-annotated genome. Exposed fish embryos were sampled for transcriptomics or chemical analysis of parent compound and primary metabolite, or observed for development and survival through larval stage. Global transcript profiling, which requires no a priori information, was applied using a large number of embryos (16) per treatment to provide a non-targeted and statistically robust approach to characterize TBPH gene expression patterns. Transcriptomic analysis revealed a dose-response in the expression of genes associated with a surprisingly limited number of biological pathways, but included the aryl hydrocarbon receptor signal transduction pathway, which is known to respond to several toxicologically-important chemical classes. These results suggest that TBPH has a relatively low potential for developmental toxicity (at least in fishes), despite concerns related to its structural similarities to endocrine disrupting chemicals, and does not present a unique gene expression pattern. More broadly, this study advances the usefulness of a biological testing and analysis system that complements current screening methods to characterize chemicals of ecological and human health concern
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Project description:The use of chemical flame-retardants (FR) in consumer products has steadily increased over the last 30 years. Toxicity data exist for legacy FRs such as pentabromodiphenyl ether (pentaBDE), but less is known about effects of new formulations. To address this issue, the toxicity of seven FR chemicals and formulations was assessed on the freshwater crustacean Daphnia magna. Acute 48-h nominal LC50 values for penta- and octabromodiphenyl ether (pentaBDE, octaBDE), Firemaster 550 (FM550), Firemaster BZ-54 (BZ54), bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP), triphenyl phosphate (TPhP), and nonbrominated BEH-TEBP analog bis(2-ethylhexyl) phthalate (BEHP) ranged from 0.058 mg/L (pentaBDE) to 3.96 mg/L (octaBDE). mRNA expression, (1)H NMR-based metabolomic and lipidomic profiling at 1/10 LC50 revealed distinct patterns of molecular response for each exposure, suggesting pentaPBDE affects transcription and translation, octaBDE and BEH-TEBP affect glycosphingolipid biosynthesis and BZ54 affects Wnt and Hedgehog signal pathways as well as glycosaminoglycan degradation. Brominated components of FM550 (i.e., BZ54) were significantly higher in Daphnia after 48 h following 1/10 LC50 exposure. FM550 elicited significant mRNA changes at five concentrations across a range from 1/10^6 LC50 to 1/2 LC50. Analyses suggest FM550 impairs nutrient utilization or uptake in Daphnia. Seven flame retardant formulations and equal volume solvent (DMSO) controls for each; four exposed and three or four biological replicates per condition.
2015-11-06 | E-GEOD-74736 | biostudies-arrayexpress