ArticleArchives of toxicology2015
MPTP's pathway of toxicity indicates central role of transcription factor SP1.
Article in Archives of toxicology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
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- Avoiding Regrettable Substitutions: Green Toxicology for Sustainable Chemistry.ACS sustainable chemistry & engineering · 2021Article
- Functionally Enigmatic Genes in Cancer: Using TCGA Data to Map the Limitations of Annotations.Scientific reports · 2020Article
- Perspectives onApplied in vitro toxicology · 2018Review
- Developments in toxicogenomics: understanding and predicting compound-induced toxicity from gene expression data.Molecular omics · 2018Review
- Weighted Gene Correlation Network Analysis (WGCNA) Reveals Novel Transcription Factors Associated With Bisphenol A Dose-Response.Frontiers in genetics · 2018Article
- Systems Toxicology: Real World Applications and Opportunities.Chemical research in toxicology · 2017Article
- Information-dependent enrichment analysis reveals time-dependent transcriptional regulation of the estrogen pathway of toxicity.Archives of toxicology · 2017Article
- Metabolomic network analysis of estrogen-stimulated MCF-7 cells: a comparison of overrepresentation analysis, quantitative enrichment analysis and pathway analysis versus metabolite network analysis.Archives of toxicology · 2017Article
- A LUHMES 3D dopaminergic neuronal model for neurotoxicity testing allowing long-term exposure and cellular resilience analysis.Archives of toxicology · 2016Article
- Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration.Archives of toxicology · 2016Article
- Developing tools for defining and establishing pathways of toxicity.Archives of toxicology · 2015Article
- From smoking guns to footprints: mining for critical events of toxicity pathways in transcriptome data.Archives of toxicology · 2015Article
- The Human Toxome Collaboratorium: A Shared Environment for Multi-Omic Computational Collaboration within a Consortium.Frontiers in pharmacology · 2015Article
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Abstract
Deriving a Pathway of Toxicity from transcriptomic data remains a challenging task. We explore the use of weighted gene correlation network analysis (WGCNA) to extract an initial network from a small microarray study of MPTP toxicity in mice. Five modules were statistically significant; each module was analyzed for gene signatures in the Chemical and Genetic Perturbation subset of the Molecular Signatures Database as well as for over-represented transcription factor binding sites and WGCNA clustered probes by function and captured pathways relevant to neurodegenerative disorders. The resulting network was analyzed for transcription factor candidates, which were narrowed down via text-mining for relevance to the disease model, and then combined with the large-scale interaction FANTOM4 database to generate a genetic regulatory network. Modules were enriched for transcription factors relevant to Parkinson's disease. Transcription factors significantly improved the number of genes that could be connected in a given component. For each module, the transcription factor that had, by far, the highest number of interactions was SP1, and it also had substantial experimental evidence of interactions. This analysis both captures much of the known biology of MPTP toxicity and suggests several candidates for further study. Furthermore, the analysis strongly suggests that SP1 plays a central role in coordinating the cellular response to MPTP toxicity.
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