Publications by authors named "Jessica Ewald"

13 Publications

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Using Transcriptomics and Metabolomics to Understand Species Differences in Sensitivity to Chlorpyrifos in Japanese Quail and Double-Crested Cormorant Embryos.

Environ Toxicol Chem 2021 Jul 22. Epub 2021 Jul 22.

Ecotoxicology and Wildlife Health Division, Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, Ontario, Canada.

Modern 21st-century toxicity testing makes use of omics technologies to address critical questions in toxicology and chemical management. Of interest are questions relating to chemical mechanisms of toxicity, differences in species sensitivity, and translation of molecular effects to observable apical endpoints. Our study addressed these questions by comparing apical outcomes and multiple omics responses in early-life stage exposure studies with Japanese quail (Coturnix japonica) and double-crested cormorant (Phalacrocorax auritus), representing a model and ecological species, respectively. Specifically, we investigated the dose-dependent response of apical outcomes as well as transcriptomics and metabolomics in the liver of each species exposed to chlorpyrifos, a widely used organophosphate pesticide. Our results revealed a clear pattern of dose-dependent disruption of gene expression and metabolic profiles in Japanese quail but not double-crested cormorant at similar chlorpyrifos exposure concentrations. The difference in sensitivity between species was likely due to higher metabolic transformation of chlorpyrifos in Japanese quail compared to double-crested cormorant. The most impacted biological pathways after chlorpyrifos exposure in Japanese quail included hepatic metabolism, oxidative stress, endocrine disruption (steroid and nonsteroid hormones), and metabolic disease (lipid and fatty acid metabolism). Importantly, we show consistent responses across biological scales, suggesting that significant disruption at the level of gene expression and metabolite profiles leads to observable apical responses at the organism level. Our study demonstrates the utility of evaluating effects at multiple biological levels of organization to understand how modern toxicity testing relates to outcomes of regulatory relevance, while also highlighting important, yet poorly understood, species differences in sensitivity to chemical exposure. Environ Toxicol Chem 2021;00:1-15. © 2021 SETAC.
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http://dx.doi.org/10.1002/etc.5174DOI Listing
July 2021

Assessing the Toxicity of 17α-Ethinylestradiol in Rainbow Trout Using a 4-Day Transcriptomics Benchmark Dose (BMD) Embryo Assay.

Environ Sci Technol 2021 08 22;55(15):10608-10618. Epub 2021 Jul 22.

Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5B3.

There is an urgent demand for more efficient and ethical approaches in ecological risk assessment. Using 17α-ethinylestradiol (EE2) as a model compound, this study established an embryo benchmark dose (BMD) assay for rainbow trout (RBT; ) to derive transcriptomic points-of-departure (tPODs) as an alternative to live-animal tests. Embryos were exposed to graded concentrations of EE2 (measured: 0, 1.13, 1.57, 6.22, 16.3, 55.1, and 169 ng/L) from hatch to 4 and up to 60 days post-hatch (dph) to assess molecular and apical responses, respectively. Whole proteome analyses of alevins did not show clear estrogenic effects. In contrast, transcriptomics revealed responses that were in agreement with apical effects, including excessive accumulation of intravascular and hepatic proteinaceous fluid and significant increases in mortality at 55.1 and 169 ng/L EE2 at later time points. Transcriptomic BMD analysis estimated the median of the 20th lowest geneBMD to be 0.18 ng/L, the most sensitive tPOD. Other estimates (0.78, 3.64, and 1.63 ng/L for the 10th percentile geneBMD, first peak geneBMD distribution, and median geneBMD of the most sensitive over-represented pathway, respectively) were within the same order of magnitude as empirically derived apical PODs for EE2 in the literature. This 4-day alternative RBT embryonic assay was effective in deriving tPODs that are protective of chronic effects of EE2.
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http://dx.doi.org/10.1021/acs.est.1c02401DOI Listing
August 2021

OmicsAnalyst: a comprehensive web-based platform for visual analytics of multi-omics data.

Nucleic Acids Res 2021 07;49(W1):W476-W482

Institute of Parasitology, McGill University, Montreal, Quebec, Canada.

Data analysis and interpretation remain a critical bottleneck in current multi-omics studies. Here, we introduce OmicsAnalyst, a user-friendly, web-based platform that allows users to perform a wide range of well-established data-driven approaches for multi-omics integration, and visually explore their results in a clear and meaningful manner. To help navigate complex landscapes of multi-omics analysis, these approaches are organized into three visual analytics tracks: (i) the correlation network analysis track, where users choose among univariate and multivariate methods to identify important features and explore their relationships in 2D or 3D networks; (ii) the cluster heatmap analysis track, where users apply several cutting-edge multi-view clustering algorithms and explore their results via interactive heatmaps; and (iii) the dimension reduction analysis track, where users choose among several recent multivariate techniques to reveal global data structures, and explore corresponding scores, loadings and biplots in interactive 3D scatter plots. The three visual analytics tracks are equipped with comprehensive options for parameter customization, view customization and targeted analysis. OmicsAnalyst lowers the access barriers to many well-established methods for multi-omics integration via novel visual analytics. It is freely available at https://www.omicsanalyst.ca.
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http://dx.doi.org/10.1093/nar/gkab394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262745PMC
July 2021

Ultrafast functional profiling of RNA-seq data for nonmodel organisms.

Genome Res 2021 Apr 17;31(4):713-720. Epub 2021 Mar 17.

Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Quebec H9X 3V9, Canada.

Computational time and cost remain a major bottleneck for RNA-seq data analysis of nonmodel organisms without reference genomes. To address this challenge, we have developed Seq2Fun, a novel, all-in-one, ultrafast tool to directly perform functional quantification of RNA-seq reads without transcriptome de novo assembly. The pipeline starts with raw read quality control: sequencing error correction, removing poly(A) tails, and joining overlapped paired-end reads. It then conducts a DNA-to-protein search by translating each read into all possible amino acid fragments and subsequently identifies possible homologous sequences in a well-curated protein database. Finally, the pipeline generates several informative outputs including gene abundance tables, pathway and species hit tables, an HTML report to visualize the results, and an output of clean reads annotated with mapped genes ready for downstream analysis. Seq2Fun does not have any intermediate steps of file writing and loading, making I/O very efficient. Seq2Fun is written in C++ and can run on a personal computer with a limited number of CPUs and memory. It can process >2,000,000 reads/min and is >120 times faster than conventional workflows based on de novo assembly, while maintaining high accuracy in our various test data sets.
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http://dx.doi.org/10.1101/gr.269894.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015844PMC
April 2021

FastBMD: an online tool for rapid benchmark dose-response analysis of transcriptomics data.

Bioinformatics 2021 05;37(7):1035-1036

Department of Natural Resource Sciences, McGill University, Montreal, QC H9X 3V9, Canada.

Motivation: Transcriptomics dose-response analysis is a promising new approach method for toxicity testing. While international regulatory agencies have spent substantial effort establishing a standardized statistical approach, existing software that follows this approach is computationally inefficient and must be locally installed.

Results: FastBMD is a web-based tool that implements standardized methods for transcriptomics benchmark dose-response analysis in R. It is >60 times faster than the current leading software, supports transcriptomics data from 13 species, and offers a comprehensive analytical pipeline that goes from processing and normalization of raw gene expression values to interactive exploration of pathway-level benchmark dose results.

Availability And Implementation: FastBMD is freely available at www.fastbmd.ca.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btaa700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128449PMC
May 2021

EcoToxModules: Custom Gene Sets to Organize and Analyze Toxicogenomics Data from Ecological Species.

Environ Sci Technol 2020 04 10;54(7):4376-4387. Epub 2020 Mar 10.

Faculty of Agricultural and Environmental Sciences, McGill University, Sainte-Anne-de-Bellevue H9X 3V9, Canada.

Traditional results from toxicogenomics studies are complex lists of significantly impacted genes or gene sets, which are challenging to synthesize down to actionable results with a clear interpretation. Here, we defined two sets of 21 custom gene sets, called the functional and statistical EcoToxModules, in fathead minnow () to (1) re-cast predefined molecular pathways into a toxicological framework and (2) provide a data-driven, unsupervised grouping of genes impacted by exposure to environmental contaminants. The functional EcoToxModules were identified by re-organizing KEGG pathways into biological processes that are more relevant to ecotoxicology based on the input from expert scientists and regulators. The statistical EcoToxModules were identified using co-expression analysis of publicly available microarray data ( = 303 profiles) measured in livers of fathead minnows after exposure to 38 different conditions. Potential applications of the EcoToxModules were demonstrated with two case studies that represent exposure to a pure chemical and to environmental wastewater samples. In comparisons to differential expression and gene set analysis, we found that EcoToxModule responses were consistent with these traditional results. Additionally, they were easier to visualize and quantitatively compare across different conditions, which facilitated drawing conclusions about the relative toxicity of the exposures within each case study.
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http://dx.doi.org/10.1021/acs.est.9b06607DOI Listing
April 2020

Selenium and stable mercury isotopes provide new insights into mercury toxicokinetics in pilot whales.

Sci Total Environ 2020 Mar 27;710:136325. Epub 2019 Dec 27.

Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, United States; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States.

High exposures of mammalian species to inorganic mercury (Hg) and methylmercury (MeHg) have been associated with adverse effects on behavior and reproduction. Different mammalian species exhibit varying responses to similar external exposure levels, reflecting potential differences in Hg toxicokinetics. Here, we use Hg stable isotopes, total Hg, MeHg and selenium (Se) concentrations measured in multiple tissues of North Atlantic pilot whales (Globicephala melas) to investigate processes affecting the distribution and accumulation of Hg and MeHg. We find that simple mixing of two distinct isotopic end-members: MeHg (1.4‰) and Hg (-1.6‰) can explain the observed variability of δHg in brain tissue. A similar isotopic composition for the MeHg end-member in the brain, muscle, heart, and kidney suggests efficient exchange of MeHg in blood throughout the body. By contrast, the Hg isotopic composition of the liver of adult whales is different from younger whales and other tissues that follow the two-end member mixing model. Measured Se:Hg ratios are lowest in adult whales with the highest levels of MeHg exposure. In these individuals, Se availability is likely reduced by complexation with demethylated Hg. We speculate that this results in a higher fraction of labile Hg eliminated from the liver of adult whales compared to young whales and subsequent redistribution to other tissues, potentially affecting toxicity.
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http://dx.doi.org/10.1016/j.scitotenv.2019.136325DOI Listing
March 2020

T1000: a reduced gene set prioritized for toxicogenomic studies.

PeerJ 2019 29;7:e7975. Epub 2019 Oct 29.

Institute of Parasitology, McGill University, Montreal, Canada.

There is growing interest within regulatory agencies and toxicological research communities to develop, test, and apply new approaches, such as toxicogenomics, to more efficiently evaluate chemical hazards. Given the complexity of analyzing thousands of genes simultaneously, there is a need to identify reduced gene sets. Though several gene sets have been defined for toxicological applications, few of these were purposefully derived using toxicogenomics data. Here, we developed and applied a systematic approach to identify 1,000 genes (called Toxicogenomics-1000 or T1000) highly responsive to chemical exposures. First, a co-expression network of 11,210 genes was built by leveraging microarray data from the Open TG-GATEs program. This network was then re-weighted based on prior knowledge of their biological (KEGG, MSigDB) and toxicological (CTD) relevance. Finally, weighted correlation network analysis was applied to identify 258 gene clusters. T1000 was defined by selecting genes from each cluster that were most associated with outcome measures. For model evaluation, we compared the performance of T1000 to that of other gene sets (L1000, S1500, Genes selected by Limma, and random set) using two external datasets based on the rat model. Additionally, a smaller (T384) and a larger version (T1500) of T1000 were used for dose-response modeling to test the effect of gene set size. Our findings demonstrated that the T1000 gene set is predictive of apical outcomes across a range of conditions (e.g., and , dose-response, multiple species, tissues, and chemicals), and generally performs as well, or better than other gene sets available.
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http://dx.doi.org/10.7717/peerj.7975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824333PMC
October 2019

Growth of Dehalococcoides spp. and increased abundance of reductive dehalogenase genes in anaerobic PCB-contaminated sediment microcosms.

Environ Sci Pollut Res Int 2020 Mar 17;27(9):8846-8858. Epub 2019 Jun 17.

Department of Civil and Environmental Engineering, IIHR-Hydroscience and Engineering, University of Iowa, Iowa City, IA, 52242, USA.

Polychlorinated biphenyls (PCBs) contaminate 19% of US Superfund sites and represent a serious risk to human and environmental health. One promising strategy to remediate PCB-contaminated sediments utilizes organohalide-respiring bacteria (OHRB) that dechlorinate PCBs.However, functional genes that act as biomarkers for PCB dechlorination processes (i.e., reductive dehalogenase genes) are poorly understood. Here, we developed anaerobic sediment microcosms that harbor an OHRB community dominated by the genus Dehalococcoides. During the 430-day microcosm incubation, Dehalococcoides 16S rRNA sequences increased two orders of magnitude to 10 copies/g of sediment, and at the same time, PCB118 decreased by as much as 70%. In addition, the OHRB community dechlorinated a range of penta- and tetra-chlorinated PCB congeners including PCBs 66, 70 + 74 + 76, 95, 90 + 101, and PCB110 without exogenous electron donor. We quantified candidate reductive dehalogenase (RDase) genes over a 430-day incubation period and found rd14, a reductive dehalogenase that belongs to Dehalococcoides mccartyi strain CG5, was enriched to 10 copies/g of sediment. At the same time, pcbA5 was enriched to only 10 copies/g of sediment. A survey for additional RDase genes revealed sequences similar to strain CG5's rd4 and rd8. In addition to demonstrating the PCB dechlorination potential of native microbial communities in contaminated freshwater sediments, our results suggest candidate functional genes with previously unexplored potential could serve as biomarkers of PCB dechlorination processes.
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http://dx.doi.org/10.1007/s11356-019-05571-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918016PMC
March 2020

NetworkAnalyst 3.0: a visual analytics platform for comprehensive gene expression profiling and meta-analysis.

Nucleic Acids Res 2019 07;47(W1):W234-W241

Institute of Parasitology, McGill University, Montreal, Quebec, Canada.

The growing application of gene expression profiling demands powerful yet user-friendly bioinformatics tools to support systems-level data understanding. NetworkAnalyst was first released in 2014 to address the key need for interpreting gene expression data within the context of protein-protein interaction (PPI) networks. It was soon updated for gene expression meta-analysis with improved workflow and performance. Over the years, NetworkAnalyst has been continuously updated based on community feedback and technology progresses. Users can now perform gene expression profiling for 17 different species. In addition to generic PPI networks, users can now create cell-type or tissue specific PPI networks, gene regulatory networks, gene co-expression networks as well as networks for toxicogenomics and pharmacogenomics studies. The resulting networks can be customized and explored in 2D, 3D as well as Virtual Reality (VR) space. For meta-analysis, users can now visually compare multiple gene lists through interactive heatmaps, enrichment networks, Venn diagrams or chord diagrams. In addition, users have the option to create their own data analysis projects, which can be saved and resumed at a later time. These new features are released together as NetworkAnalyst 3.0, freely available at https://www.networkanalyst.ca.
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http://dx.doi.org/10.1093/nar/gkz240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602507PMC
July 2019

Organ-specific differences in mercury speciation and accumulation across ringed seal (Phoca hispida) life stages.

Sci Total Environ 2019 Feb 25;650(Pt 2):2013-2020. Epub 2018 Sep 25.

Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, United States; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States.

Methylmercury (MeHg) is a central nervous system toxicant and exposures can adversely affect the health of marine mammals. Mercuric selenide (HgSe) in marine mammal tissues is hypothesized to result from a protective detoxification mechanism, but toxicokinetic processes contributing to its formation are poorly understood. Here, new data is reported on speciated Hg concentrations in multiple organs of n = 56 ringed seals (Phoca hispida) from Labrador, Canada, and compare concentrations to previously published data from Greenland seals. A higher proportion of Hg is found to accumulate in the kidney of young-of-the-year (YOY) ringed seals compared to adults. A toxicokinetic model for Hg species is developed and evaluated to better understand factors affecting variability in Hg concentrations among organs and across life stages. Prior work postulated that HgSe formation only occurs in the liver of mature seals, but model results suggest HgSe formation occurs across all life stages. Higher proportions of HgSe in mature seal livers compared to YOY seals likely results from the slow accumulation and elimination of HgSe (total body half-life = 500 days) compared to other Hg species. HgSe formation in the liver reduces modeled blood concentrations of MeHg by only 6%. Thus, HgSe formation may not substantially reduce MeHg transport across the blood-brain barrier of ringed seals, leaving them susceptible to the neurotoxic effects of MeHg exposure.
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http://dx.doi.org/10.1016/j.scitotenv.2018.09.299DOI Listing
February 2019

PCB dechlorination hotspots and reductive dehalogenase genes in sediments from a contaminated wastewater lagoon.

Environ Sci Pollut Res Int 2018 Jun 12;25(17):16376-16388. Epub 2017 Aug 12.

Department of Civil and Environmental Engineering, University of Iowa, 4105 Seamans Center, Iowa City, IA, 52242, USA.

Polychlorinated biphenyls (PCBs) are a class of persistent organic pollutants that are distributed worldwide. Although industrial PCB production has stopped, legacy contamination can be traced to several different commercial mixtures (e.g., Aroclors in the USA). Despite their persistence, PCBs are subject to naturally occurring biodegradation processes, although the microbes and enzymes involved are poorly understood. The biodegradation potential of PCB-contaminated sediments in a wastewater lagoon located in Virginia (USA) was studied. Total PCB concentrations in sediments ranged from 6.34 to 12,700 mg/kg. PCB congener profiles in sediment sample were similar to Aroclor 1248; however, PCB congener profiles at several locations showed evidence of dechlorination. The sediment microbial community structure varied among samples but was dominated by Proteobacteria and Firmicutes. The relative abundance of putative dechlorinating Chloroflexi (including Dehalococcoides sp.) was 0.01-0.19% among the sediment samples, with Dehalococcoides sp. representing 0.6-14.8% of this group. Other possible PCB dechlorinators present included the Clostridia and the Geobacteraceae. A PCR survey for potential PCB reductive dehalogenase genes (RDases) yielded 11 sequences related to RDase genes in PCB-respiring Dehalococcoides mccartyi strain CG5 and PCB-dechlorinating D. mccartyi strain CBDB1. This is the first study to retrieve potential PCB RDase genes from unenriched PCB-contaminated sediments.
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http://dx.doi.org/10.1007/s11356-017-9872-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206866PMC
June 2018

Environmental Origins of Methylmercury Accumulated in Subarctic Estuarine Fish Indicated by Mercury Stable Isotopes.

Environ Sci Technol 2016 11 19;50(21):11559-11568. Epub 2016 Oct 19.

Department of Environmental Health, Harvard T. H. Chan School of Public Health , Boston, Massachusetts 02115, United States.

Methylmercury (MeHg) exposure can cause adverse reproductive and neurodevelopmental health effects. Estuarine fish may be exposed to MeHg produced in rivers and their watersheds, benthic sediment, and the marine water column, but the relative importance of each source is poorly understood. We measured stable isotopes of mercury (δHg, ΔHg, and ΔHg), carbon (δC), and nitrogen (δN) in fish with contrasting habitats from a large subarctic coastal ecosystem to better understand MeHg exposure sources. We identify two distinct food chains exposed to predominantly freshwater and marine MeHg sources but do not find evidence for a benthic marine MeHg signature. This is consistent with our previous research showing benthic sediment is a net sink for MeHg in the estuary. Marine fish display lower and less variable ΔHg values (0.78‰ to 1.77‰) than freshwater fish (0.72‰ to 3.14‰) and higher δHg values (marine: 0.1‰ to 0.57‰; freshwater: -0.76‰ to 0.15‰). We observe a shift in the Hg isotopic composition of juvenile and adult rainbow smelt (Osmerus mordax) when they transition between the freshwater and marine environment as their dominant foraging territory. The Hg isotopic composition of Atlantic salmon (Salmo salar) indicates they receive most of their MeHg from the marine environment despite a similar or longer duration spent in freshwater regions. We conclude that stable Hg isotopes effectively track fish MeHg exposure sources across different ontogenic stages.
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http://dx.doi.org/10.1021/acs.est.6b03206DOI Listing
November 2016
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