Transcriptional profiling reveals barcode-like toxicogenomic responses in the zebrafish embryo

Yang, Lixin; Kemadjou, Jules R; Zinsmeister, Christian; Bauer, Matthias; Legradi, Jessica; Müller, Ferenc; Pankratz, Michael J.; Jäkel, Jens; Strähle, Uwe

doi:10.1186/gb-2007-8-10-r227

Cited by 177 publications

(117 citation statements)

References 200 publications

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“…Other studies also support the observation that exposure to mercury results in tail deformities in ZFEs [57,58,62]. The study by Yang et al [57] suggests that methyl mercury specifically impairs tail development in part through activation of matrix metalloproteases 9 and 13, which are active in tissue remodelling.…”

Section: Methylmentioning

confidence: 71%

“…Low concentrations of methyl mercury also have adverse affects on ZFE development [45,[55][56][57]. Similar studies examined the use of ZFEs specifically to assess environmental water contamination Yang et al [58] observations that ZFEs are highly sensitive to adverse effects of exposure to mercury and the Lahnsteiner [59] study also reported that the first 24 h of ZFE development was the most sensitive period for exposure to various environmental contaminants, including HgCl 2 .…”

Section: Methylmentioning

confidence: 99%

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Early Exposure to Mercuric Chloride or Methylmercury Alters Zebrafish Embryo (Danio rerio) Development

Abbott¹

2017

Poult Fish Wildl Sci

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Environmental mercury contamination is ubiquitous and toxic to developing embryos. Zebra fish embryos (ZFEs) were exposed for 24 h to different concentrations of mercuric chloride or methyl mercury. Exposure to 100 µg/L methyl mercury and 1000 µg/L mercuric chloride resulted in 100% mortality. ZFEs exposed to 100 µg/L or higher mercuric chloride exhibited decreased body length, deformed tails and reduced eye volume. Using Proliferating Cell Nuclear Antigen (PCNA) immunohistochemistry assessment at 30 h post fertilization, we determined that exposure to mercuric chloride did not alter cell proliferation in the developing brain. These ZFE data were compared to results obtained with methyl mercury exposure; both compounds produced delayed toxicity and methyl mercury is more toxic than mercuric chloride at equal concentrations.

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Section: Methylmentioning

confidence: 71%

Section: Methylmentioning

confidence: 99%

Early Exposure to Mercuric Chloride or Methylmercury Alters Zebrafish Embryo (Danio rerio) Development

Abbott¹

2017

Poult Fish Wildl Sci

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“…This robustness indicator allows reducing data dimensionality to a manageable set of variables that can be used in environmental assessment. These patterns of gene expression (Bfingerprints,^Bbarcodes^) could be used as biomarkers identifying relevant toxicants (Aardema and MacGregor 2002;Yang et al 2007;Piña and Barata 2011). With robust indicator genes, the full potential of transcriptomics can be used.…”

Section: Discussionmentioning

confidence: 99%

“…on zebrafish (Danio rerio) (Hollert et al 2003;Höss et al 2010;Feiler et al 2013). Zebrafish embryos have become a useful model organism in ecotoxicology and ecotoxicogenomics (Yang et al 2007;Strähle et al 2012;Busquet et al 2014;Schiwy et al 2014). Recent research focused on linking gene expression analysis to current assessment methods for zebrafish embryos making it possible to investigate mechanism-specific toxicity at molecular level (Keiter et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Fold-change threshold screening: a robust algorithm to unmask hidden gene expression patterns in noisy aggregated transcriptome data

Hausen

Otte

Strähle

et al. 2015

Environ Sci Pollut Res

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Transcriptomics is often used to investigate changes in an organism's genetic response to environmental contamination. Data noise can mask the effects of contaminants making it difficult to detect responding genes. Because the number of genes which are found differentially expressed in transcriptome data is often very large, algorithms are needed to reduce the number down to a few robust discriminative genes. We present an algorithm for aggregated analysis of transcriptome data which uses multiple fold-change thresholds (threshold screening) and p values from Bayesian generalized linear model in order to assess the robustness of a gene as a potential indicator for the treatments tested. The algorithm provides a robustness indicator (ROBI) as well as a significance profile, which can be used to assess the statistical significance of a given gene for different fold-change thresholds. Using ROBI, eight discriminative genes were identified from an exemplary dataset (Danio rerio FET treated with chlorpyrifos, methylmercury, and PCB) which could be potential indicators for a given substance. Significance profiles uncovered genetic effects and revealed appropriate fold-change thresholds for single genes or gene clusters. Fold-change threshold screening is a powerful tool for dimensionality reduction and feature selection in transcriptome data, as it effectively reduces the number of detected genes suitable for environmental monitoring. In addition, it is able to unmask patterns in altered genetic expression hidden by data noise and reduces the chance of type II errors, e.g., in environmental screening.

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“…Toxicogenomics has been selected as an experimental approach as it enables unbiased, global profiling of the molecular biological response space (Richard, 2006;Edwards and Preston, 2008), without preselection of response parameters. For single chemicals, it has been shown that exposure results in chemical-specific, gene expression profiles (Hamadeh et al, 2002;Yang et al, 2007;Kiyosawa et al, 2010;Janssens et al, 2011;Piña and Barata, 2011;Meganathan et al, 2012;Theunissen et al, 2012). The hypothesis tested in the present study is whether specific MoAs have common gene expression profiles that can be used to classify compounds and whether compounds with multiple MoAs can be classified and distinguished from those with only one MoA.…”

Section: Introductionmentioning

confidence: 93%

Mode of Action Assignment of Chemicals Using Toxicogenomics: A Case Study with Oxidative Uncouplers

Hawliczek-Ignarski

Cenijn²,

Legler³

et al. 2017

Front. Environ. Sci.

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A criterion frequently used to group chemicals in risk assessment is "mode of toxic action" (MoA). Routinely, structure-based approaches are used for the MoA categorization of chemicals, but they can produce conflicting results or fail to classify compounds. Biological activity-based approaches such as toxicogenomics which provide an unbiased overview of the transcriptomic changes after exposure to a compound may complement structure-based approaches in MoA assignment. Here, we investigate whether toxicogenomic profiles as generated after in vitro exposure of an established cell line (C3A hepatoma cells) are able to group together chemicals with an uncoupling MoA, and to distinguish the uncouplers from chemicals with other MoAs. In a first step, we examined whether chemicals sharing the same uncoupling of oxidative phosphorylation (OXPHOS) MoA produce similar toxicogenomic profiles and can be grouped together. In a next step, we tested whether the toxicogenomic profiles discriminate between OXPHOS and chemicals displaying a (polar) narcotic MoA. Experimentally, cells were exposed in vitro to equipotent concentrations of the test compounds and gene expression profiles were measured. The resulting toxicogenomic profiles assigned OXPHOS to one cluster and discriminated between the OXPHOS and the (polar) narcotics. In addition, the toxicogenomics data revealed that one and the same chemical can display multiple MoAs, which may help to explain conflicting results of MoA classification from structure-based approaches. The results strongly suggest the feasibility of MoA grouping of chemicals by using in vitro cell assay-based toxicogenomic profiles.

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Transcriptional profiling reveals barcode-like toxicogenomic responses in the zebrafish embryo

Cited by 177 publications

References 200 publications

Early Exposure to Mercuric Chloride or Methylmercury Alters Zebrafish Embryo (Danio rerio) Development

Early Exposure to Mercuric Chloride or Methylmercury Alters Zebrafish Embryo (Danio rerio) Development

Fold-change threshold screening: a robust algorithm to unmask hidden gene expression patterns in noisy aggregated transcriptome data

Mode of Action Assignment of Chemicals Using Toxicogenomics: A Case Study with Oxidative Uncouplers

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