- Datasets
Datasets
Create datasets to upload and publish data. Further organize your data using folders and assign metadata at both the file and dataset level.
ROAR 2701 Laboratory OPs_GLTED
U.S. EPA, GLTED laboratory operating procedures associated with ROAR project 2701. Note, all procedures are for research and development purposes and subject to change based on performance over the course of the research. Major updates will be provided as new versions.
- 0 2 0 881 1
Transcriptomics-based points of departure for Daphnia magna exposed to 18 per- and polyfluoroalkyl substances.
Daphnia magna were exposed to multiple concentrations of 22 different PFAS for 24 h, in 96-well plate format. Following exposure, whole body RNA was extracted and extracts, each representing five exposed individuals, were subjected to RNA sequencing. Following analytical measurements to verify PFAS exposure concentrations, and quality control on processed cDNA libraries for sequencing, concentration-response modeling was applied to the data sets for 18 of the tested compounds, and the concentration at which a concerted molecular response occurred (transcriptomic point of departure; tPOD) was calculated. This file provides the processed and normalized count matrices for each of the 18 PFAS evaluated along with exported results from BMDExpress 3.0 (tab delimited .txt files).
Raw data were submitted to the National Center for Biotechnology Information Sequence Read Archive (Bioproject PRJNA1018977) and Gene Expression Omnibus (GEO Accession GSE245268). Sample meta data copied here.
- 0 40 0 1533 12
Zebrafish embryo/larval toxicity testing with PFAS to address uncertainties in transcriptomic point of departure estimates across species.
Background:
Mounting evidence suggests that chemical concentrations that do not elicit concerted molecular responses over relatively short exposure durations (e.g., 24 h to 5 d) generally do not elicit adverse effects, even over much longer exposure durations. This has led to proposals to implement an omics-based regulatory testing paradigm which would use transcriptomic points of departure (tPOD; a benchmark dose/concentration -based treatment level below which a concerted gene expression response is not observed) as a health protective exposure level for risk assessment (Johnson et al. 2022). While initial research on the application of tPODs has focused on human health protection, more recently our research team and others have started to explore application of this concept for ecosystem protection as well. To evaluate the scientific underpinnings of the approach, two critical questions as it pertains to regulatory application are:
1) How variable are tPODs as a function of common experimental design variables?
2) How do tPODs for the same chemical compare across species?
To examine these questions, zebrafish (Danio rerio) embryos were exposed to three different per- or polyfluoroalkyl substances (PFAS), perfluorooctanesulfonic acid (PFOS; DTXSID3031864); perfluorooctanoic acid (PFOA; DTXSID8031865); and perfluorohexane sulfonate (PFHxS; DTXSID90892476) in concentration-response, and then whole-body gene expression was determined using RNA sequencing (RNAseq). Embryos were exposed to each of the three PFAS, as well as a chlorpyrifos positive control, over seven distinct exposure periods (6 hours post fertilization [hpf]-120 hpf; 6 hpf-48 hpf; 6 hpf-24 hpf; 24-48 hpf; 24 hpf – 120 hpf; 48 hpf-120 hpf; and 96 hpf-120 hpf; Figure 1) with the goal of determining how much the tPOD varies as a function of the developmental window over which the organisms were exposed. In a separate study (CSS.1.7.5), tPODs for PFOS, PFOA, and PFHxS were generated for several other species including fathead minnow (Pimephales promelas), Daphnia magna (a crustacean), Chironomous dilutus (an insect) and Raphidocelis subcapitata (an algae). Thus, the tPODs generated for zebrafish embryos can also be compared against these data.
Dataset:
Processed RNAseq data are provided as normalized count matrices (counts per million reads; filtered to remove genes with <15 reads across all samples; log2 transformed with a pseudo count of 1 added to avoid negative value) with individual genes as rows and samples as columns. Data sets are organized into 21 count matrices, one for each exposure window evaluated for each chemical (T1-T7; Table 1). A meta-data file that that defines the exposure window, test chemical, treatment concentration, and replicate number for each sample is also provided. RNAseq was repeated for a sub-set of samples. Repeated samples are indicated in the metadata file.
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- 0 3 0 720 4
Plots
This includes a zip file of plots by assay source.
- 0 1 0 2594 384
Summary_Files
This includes a zip file of summary files with descriptions available in README. Corrections: -mc6 method descriptions were missing in method list output file (see 11OCT2023 file) -"CytoPt" files referenced as being included in zip within Summary README had been renamed as "cytotox" files (README corrected 8JAN2024) -Uploaded annotations, gene mappings, and cytotox files so they can be linked outside of zip file -Uploaded v4.1 tcplVarMat output (variable matrices of hitcall and ac50s)
- 0 8 0 5020 536
ToxRefDB - NTP Source Documents
Space for NTP reports so they can be curated for ToxRefDB using the DCT.
- 0 2 0 593 1
Release_Note
This .html output from Rmarkdown that describes the update of invitrodb between versions 3.5 and 4.1. Invitrodb version 4.1 represents the first full release of the ToxCast database in a new schema designed to accommodate the R package dependency, tcplFit2, which is used in curve-fitting and hit-calling of multi-concentration response data. This invitrodb schema was beta-tested with our research release of invitrodb v4.0 to accompany the manuscript, “The ToxCast Pipeline: Updates to Curve-Fitting Approaches and Database Structure” and release of tcpl v3.0.1.
- 0 1 0 2011 79
AOP-Wiki xml for derivation and evaluation of cross-species AOP network for thyroid hormone system disruption
Thyroid hormone system disrupting compounds are considered potential threats for human and environmental health. Multiple adverse outcome pathways (AOPs) for thyroid hormone system disruption (THSD) are being developed in different taxa. Combining these AOPs results in a cross-species AOP network for THSD which may provide an evidence-based foundation for extrapolating THSD data across vertebrate species and bridging the gap between human and environmental health. This review aimed to advance the description of the taxonomic domain of applicability (tDOA) in the network to improve its utility for cross-species extrapolation. We focused on the molecular initiating events (MIEs) and adverse outcomes (AOs) and evaluated both their plausible domain of applicability (taxa they are likely applicable to) and empirical domain of applicability (where evidence for applicability to various taxa exists) in a THSD context.
The evaluation showed that all MIEs in the AOP network are applicable to mammals. With some exceptions, there was evidence of structural conservation across vertebrate taxa and especially for fish and amphibians, and to a lesser extent for birds, empirical evidence was found. Current evidence supports the applicability of impaired neurodevelopment, neurosensory development (e.g., vision) and reproduction across vertebrate taxa. The results of this tDOA evaluation are summarized in a conceptual AOP network that helps prioritize (parts of) AOPs for a more detailed evaluation. In conclusion, this review advances the tDOA description of an existing THSD AOP network and serves as a catalog summarizing plausible and empirical evidence on which future cross-species AOP development and tDOA assessment could build.
- 0 4 0 2309 2
MYSQL_Data
This includes a sql dump of invitrodb v4.1 with descriptions available in README.
- 0 2 0 4733 612
Supp Files and Code for Paul Friedman et al., "Reproducibility of organ-level effects in repeat dose animal studies"
Supplemental File 1 contains the datasets used in MLR for estimation of variance.
Supplemental File 2 contains tabular reporting of input data for concordance analysis and results as percent concordance observed by chemical-endpoint, chemical-endpoint-species, and chemical-endpoint-study type combinations.
Supplemental File 3 contains MLR study descriptors and results for quantitative estimates of variance.
Supplemental File 4 contains odds ratio datasets and results.
Supplemental File 5 contains summarized LEL and HED values, ToxCast assay endpoint information, and calculated AED50 values using library(httk) v2.2.2.
Supplemental File 6 contains the R code used for this analysis and figures in this work, available as a knitted R Markdown file (exported as html). The code (performed with R version 4.2.1).
Supplemental File 7 contains Supplemental Figures 1, 2, and 3.
- 0 7 0 1913 3
tcpl v3 and invitrodb v4.0
Supplemental files to accompany Feshuk et al., "The ToxCast Pipeline: Updates to Curve-fitting Approaches and Database Structure", DOI https://doi.org/10.3389/ftox.2023.1275980, PMC10552852
- 0 4 0 2089 8
Raw data were submitted to the National Center for Biotechnology Information Sequence Read Archive (Bioproject PRJNA1018977) and Gene Expression Omnibus (GEO Accession GSE245268). Sample meta data copied here.
Mounting evidence suggests that chemical concentrations that do not elicit concerted molecular responses over relatively short exposure durations (e.g., 24 h to 5 d) generally do not elicit adverse effects, even over much longer exposure durations. This has led to proposals to implement an omics-based regulatory testing paradigm which would use transcriptomic points of departure (tPOD; a benchmark dose/concentration -based treatment level below which a concerted gene expression response is not observed) as a health protective exposure level for risk assessment (Johnson et al. 2022). While initial research on the application of tPODs has focused on human health protection, more recently our research team and others have started to explore application of this concept for ecosystem protection as well. To evaluate the scientific underpinnings of the approach, two critical questions as it pertains to regulatory application are:
1) How variable are tPODs as a function of common experimental design variables?
2) How do tPODs for the same chemical compare across species?
To examine these questions, zebrafish (Danio rerio) embryos were exposed to three different per- or polyfluoroalkyl substances (PFAS), perfluorooctanesulfonic acid (PFOS; DTXSID3031864); perfluorooctanoic acid (PFOA; DTXSID8031865); and perfluorohexane sulfonate (PFHxS; DTXSID90892476) in concentration-response, and then whole-body gene expression was determined using RNA sequencing (RNAseq). Embryos were exposed to each of the three PFAS, as well as a chlorpyrifos positive control, over seven distinct exposure periods (6 hours post fertilization [hpf]-120 hpf; 6 hpf-48 hpf; 6 hpf-24 hpf; 24-48 hpf; 24 hpf – 120 hpf; 48 hpf-120 hpf; and 96 hpf-120 hpf; Figure 1) with the goal of determining how much the tPOD varies as a function of the developmental window over which the organisms were exposed. In a separate study (CSS.1.7.5), tPODs for PFOS, PFOA, and PFHxS were generated for several other species including fathead minnow (Pimephales promelas), Daphnia magna (a crustacean), Chironomous dilutus (an insect) and Raphidocelis subcapitata (an algae). Thus, the tPODs generated for zebrafish embryos can also be compared against these data.
Dataset:
Processed RNAseq data are provided as normalized count matrices (counts per million reads; filtered to remove genes with <15 reads across all samples; log2 transformed with a pseudo count of 1 added to avoid negative value) with individual genes as rows and samples as columns. Data sets are organized into 21 count matrices, one for each exposure window evaluated for each chemical (T1-T7; Table 1). A meta-data file that that defines the exposure window, test chemical, treatment concentration, and replicate number for each sample is also provided. RNAseq was repeated for a sub-set of samples. Repeated samples are indicated in the metadata file.
The evaluation showed that all MIEs in the AOP network are applicable to mammals. With some exceptions, there was evidence of structural conservation across vertebrate taxa and especially for fish and amphibians, and to a lesser extent for birds, empirical evidence was found. Current evidence supports the applicability of impaired neurodevelopment, neurosensory development (e.g., vision) and reproduction across vertebrate taxa. The results of this tDOA evaluation are summarized in a conceptual AOP network that helps prioritize (parts of) AOPs for a more detailed evaluation. In conclusion, this review advances the tDOA description of an existing THSD AOP network and serves as a catalog summarizing plausible and empirical evidence on which future cross-species AOP development and tDOA assessment could build.
Supplemental File 2 contains tabular reporting of input data for concordance analysis and results as percent concordance observed by chemical-endpoint, chemical-endpoint-species, and chemical-endpoint-study type combinations.
Supplemental File 3 contains MLR study descriptors and results for quantitative estimates of variance.
Supplemental File 4 contains odds ratio datasets and results.
Supplemental File 5 contains summarized LEL and HED values, ToxCast assay endpoint information, and calculated AED50 values using library(httk) v2.2.2.
Supplemental File 6 contains the R code used for this analysis and figures in this work, available as a knitted R Markdown file (exported as html). The code (performed with R version 4.2.1).
Supplemental File 7 contains Supplemental Figures 1, 2, and 3.