Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1046413 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26980900_1.fastq.gz | Fastqsanger.gz | |||
| SRR26980900_2.fastq.gz | Fastqsanger.gz | |||
| SRR26981000_1.fastq.gz | Fastqsanger.gz | |||
| SRR26981000_2.fastq.gz | Fastqsanger.gz | |||
| SRR26981100_1.fastq.gz | Fastqsanger.gz |
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Project description:It is postulated that below a transcriptomic-based point of departure, adverse effects are unlikely to occur, thereby providing a chemical concentration to use in screening level hazard assessment. The present study extends previous work describing a high throughput fathead minnow assay that can provide full transcriptomic data after exposure to a test chemical. One day post-hatch fathead minnows were exposed to ten concentrations of three representatives of four chemical modes of action: organophosphates, ecdysone receptor agonists, plant photosystem II inhibitors, and estrogen receptor agonists for 24 hours. Concentration response modeling was performed on whole body gene expression data from each exposure, using measured chemical concentrations when available. Transcriptomic points of departure in larval fathead minnow were lower than apical effect concentrations across fish species but not always lower than toxic effect concentrations in other aquatic taxa like crustaceans and insects. The point of departure was highly dependent on measured chemical concentration which were often lower than the nominal concentration. Differentially expressed genes between chemicals within modes of action were compared and often showed statistically significant overlap. In addition, reproducibility between identical exposures using a positive control chemical (CuSO4) and variability associated with the transcriptomic point of departure using in-silico sampling were considered. Results extend a transcriptomic-compatible fathead minnow high throughput assay for possible use in ecological hazard screening.
2024-10-18 | GSE252223 | GEO
Project description:RNA-seq expression assays were done in larval Pimephales promelas (Fathead minnow, FHM) exposed to 10 chemicals (3 metals, 4 Neonicotinoids, and 3 pharmaceuticals) over a range of concentrations to derive relatively short term transcriptomics based points of departure (tPODs). tPODs were compared to apical points of departures (aPODs) to investigate the potential use of the FHM tPODS as part of a high throughput approach that might be used in a regulatory context.
2023-01-01 | GSE207231 | GEO
Project description:There is a need to generate hazard information for chemicals already in production. This can be costly and time consuming. Higher-throughput techniques offer a method to effectively contextualize and define the hazard potential posed by chemicals and facilitate risk assessment activities in a rapid manner. Transcriptomic points of departure (tPODs), derived from the concentration at which global gene expression significantly differs from controls, are expected to precede apical toxicity. Therefore, concentrations below that elicit modulation of gene expression would be unlikely to cause adverse effects, suggesting tPODs could serve as an alternative point of departure for use in screening level hazard assessment. The present study extends previous work with a larval fathead minnow high-throughput transcriptomics assay but employed a targeted transcriptome rather than whole transcriptome approach to generate tPODs for 22 chemicals (pesticides and pharmaceuticals), expanding the diversity of chemical modes of action evaluated. One day post hatch fathead minnows were exposed to eight concentrations of two piscicides, three herbicides, four insecticides, seven fungicides, two statins, and four PPAR agonists for 24 h. Following exposures, whole body homogenates were sent for targeted RNA sequencing using TempO-Seq. Concentration response modeling, using measured concentrations where feasible, was applied to all sequencing results to estimate benchmark concentrations and derive tPODs. The derived tPODs were lower than concentrations that impacted apical endpoints in fish collected from the ECOTOX Knowledgebase in most cases. However, this was not the case when compared to apical effects in other taxa (crustaceans, insects, algae). To investigate the relationships of chemicals within the same mode of action (MoA), exploratory principal component analysis was used as was examining differentially expressed genes between chemicals within modes of action. Our results showed that the individual genes impacted by chemical exposure rarely clustered within modes of action. The results of this study provide additional data that can be used to examine the applicability of high-throughput assay for possible use in ecological hazard screening
2026-05-21 | GSE300125 | GEO
Project description:Traditional toxicity testing has been unable to keep pace with the introduction of new chemicals into commerce. Consequently, there are limited or no toxicity data upon which to base a risk assessment for many chemicals to which fish and wildlife may be exposed. Per- and polyfluoroalkyl substances (PFAS) are emblematic of this issue in that most the ecological hazards of most PFAS remain uncharacterized. The present study employed a high throughput assay to identify the concentration at which 20 PFAS, with diverse properties, elicited a concerted gene expression response in larval fathead minnows (Pimephales promelas, 5-6 days post-fertilization) exposed for 24 h. Based on a reduced transcriptome approach that measured whole body expression of 1832 genes, the median transcriptomic point of departure (tPOD) for the 20 PFAS tested was 10 µM. Longer chain carboxylic acids (12-13 C-F) and an eight C-F di-alcohol, N-alkyl sulfonamide, and telomer sulfonic acid were among the most potent PFAS, eliciting gene expression responses at concentrations below 1 µM. With a few exceptions, larval fathead minnow tPODs were concordant with those based on whole transcriptome response in human cell lines. However, larval fathead minnow tPODs were often greater than those for Daphnia magna exposed to the same PFAS. The tPODs overlapped concentrations at which other sub-lethal effects have been reported in fish (available for 10 PFAS; including a range of species, life stages, and study designs). Nonetheless, fathead minnow tPODs were all orders of magnitude higher than aqueous PFAS concentrations detected in tributaries of the North American Great Lakes suggesting a substantial margin of safety in those systems, even for PFAS with significant potential for bioaccumulation. Overall, results broadly support the use of a fathead minnow larval transcriptomics assay to derive screening level potency estimates for use in ecological risk-based prioritization. Traditional toxicity testing has been unable to keep pace with the introduction of new chemicals into commerce. Consequently, there are limited or no toxicity data upon which to base a risk assessment for many chemicals to which fish and wildlife may be exposed. Per- and polyfluoroalkyl substances (PFAS) are emblematic of this issue in that most the ecological hazards of most PFAS remain uncharacterized. The present study employed a high throughput assay to identify the concentration at which 20 PFAS, with diverse properties, elicited a concerted gene expression response in larval fathead minnows (Pimephales promelas, 5-6 days post-fertilization) exposed for 24 h. Based on a reduced transcriptome approach that measured whole body expression of 1832 genes, the median transcriptomic point of departure (tPOD) for the 20 PFAS tested was 10 µM. Longer chain carboxylic acids (12-13 C-F) and an eight C-F di-alcohol, N-alkyl sulfonamide, and telomer sulfonic acid were among the most potent PFAS, eliciting gene expression responses at concentrations below 1 µM. With a few exceptions, larval fathead minnow tPODs were concordant with those based on whole transcriptome response in human cell lines. However, larval fathead minnow tPODs were often greater than those for Daphnia magna exposed to the same PFAS. The tPODs overlapped concentrations at which other sub-lethal effects have been reported in fish (available for 10 PFAS; including a range of species, life stages, and study designs). Nonetheless, fathead minnow tPODs were all orders of magnitude higher than aqueous PFAS concentrations detected in tributaries of the North American Great Lakes suggesting a substantial margin of safety in those systems, even for PFAS with significant potential for bioaccumulation. Overall, results broadly support the use of a fathead minnow larval transcriptomics assay to derive screening level potency estimates for use in ecological risk-based prioritization.
2024-10-23 | GSE246120 | GEO
Project description:In this study, fathead minnow larvae were exposed to eight concentrations of two glucocorticoid receptor agonists, dexamethasone and fluticasone, and assessed transcriptome-wide gene expression changes using RNA-seq. Differential gene expression analysis revealed substantial overlap in affected genes between the two compounds, supporting their shared mechanism of action. Transcriptomic points of departure (tPODs) were calculated to identify concentrations at which early transcriptomic responses would likely occur. Functional enrichment analysis identified activated biological pathways and enabled the calculation of biological pathway altering concentrations (BPACs). Both compounds significantly altered pathways related to glucocorticoid activity, with fluticasone showing higher potency in most of the pathways. The significant overlap in differentially expressed genes and enriched pathways provides evidence that transcriptomic profiling can effectively detect shared mechanisms of action between related compounds. These findings support the utility of RNA-seq data in read-across approaches for chemical risk assessment and highlight the conserved molecular responses to glucocorticoid receptor activation in fathead minnows.
2026-04-10 | GSE294459 | GEO
Project description:Current methods to support chemical hazard assessment face significant challenges given the rapidly growing number of compounds of emerging concern (CEC) requiring assessment. Standard testing strategies rely upon live animal testing, which are time-consuming, expensive, and ethically questionable. These concerns serve as an impetus to develop new approach methodologies (NAMs) that do not rely on live animal tests. This study explored the application of the molecular benchmark dose (BMD) approach in a 7-day embryo-larval fathead minnow (FHM) assay to derive determine transcriptomic points-of-departure (tPODs) which can be useds to predict apical BMDs of fluoxetine (FLX), a highly prescribed and potent selective serotonin reuptake inhibitor frequently detected in surface waters. Fertilized FHM embryos were exposed to graded concentrations of FLX (confirmed at <LOD, 0.19, 0.74, 3.38, 10.2, 47.5 µg/L) for 32 days. Subsets of fish were subjected to omics and locomotor analyses at 7 days post-fertilization (dpf) and to histological and biometric measurements at 32 dpf. Enrichment analyses of transcriptomics and proteomics data revealed significant perturbations in gene sets associated with serotonergic and axonal functions. BMD analysis resulted in tPOD values of 0.56 µg/L (median of the 20 most sensitive gene-level BMDs), 5.0 µg/L (tenth percentile of all gene-level BMDs), 7.51 µg/L (mode of the first peak of all gene-level BMDs) , and 5.66 µg/L (pathway-level BMD). These tPODs are protective of apical locomotor and reduced weight effects (LOEC of 10.2 µg/L) observed in this study and are well within the range of chronic apical BMDs of FLX reported in the literature. Furthermore, the distribution of gene-level BMDs followed a bimodal pattern, revealing disruption of sensitive neurotoxic pathways at low concentrations and metabolic pathway perturbations at higher concentrations. This is one of the first studies to derive tPODs for FLX using a short-term embryo assay at a life stage not considered to be a live animal under current legislations.
2021-12-12 | GSE179232 | GEO
Project description:Humans are regularly exposed to mixtures of BPA alternative chemicals through their diets, consumer products and other sources. Like BPA, many alternatives perturb nuclear hormone receptors and are considered endocrine disrupting chemicals. We used high-throughput transcriptomics (HTTr) to evaluate the potency and potential modes of action of seven mixtures of BPA alternatives, along with their 12 individual components, in MCF-7 breast cancer cells. Our primary aim was to explore whether alternatives present in mixtures act additively. MCF-7 cells were exposed to chemicals (0.001 – 50 µM) for 48 h in serum-free conditions and TempO-Seq (BioSypder Inc.) was used to determine global and estrogen receptor alpha (ERα)-specific transcriptomic changes. Transcriptomic points of departure were derived using benchmark concentration (BMC) modelling. We first identified the concentration at which global transcriptional activity was robustly altered. Then, a novel ERα transcriptomic biomarker was used to identify ERα agonists and model a predicted ERα activation point of departure. Mixtures modelling was employed to predict potency of BPA alternatives and test for additive effects in vitro. Ingenuity Pathway Analysis (IPA; Qiagen) was used to identify upstream regulators and canonical pathways from genes fitting BMCs. All seven mixtures had additive effects across all transcriptomic points of departure modelled. BPAF was the most potent individual chemical tested overall, followed by BPA and BPC. The ERα transcriptomic biomarker classified all mixtures as ERα activators along with several individual BPA alternatives. Pathway analysis revealed that all mixtures and most individual components perturbed similar upstream regulators and pathways, suggesting common modes of action. These data support the use of HTTr as part of new approach methodologies to assess the toxicological potency of mixtures in vitro.
2025-06-30 | GSE276869 | GEO
Project description:Short-term transcriptomic points-of-departure are consistent with chronic points-of departure for three organophosphate pesticides across mouse and fathead minnow.
| PRJNA1005574 | ENA
Project description:Comparative analysis of transcriptomic points-of-departure (tPODs) and adverse apical responses in embryo-larval fathead minnows exposed to fluoxetine
| PRJNA742771 | ENA
Project description:Fathead minnow ovary explants were incubated with DHT at 10^-6M for 6, 9, and 12 hours. Estrogen production was significantly increased in these ovaries at all three time points.
2012-07-31 | GSE38289 | GEO