ArticleToxicological sciences : an official journal of the Society of Toxicology2017
Editor's Highlight: Application of Gene Set Enrichment Analysis for Identification of Chemically Induced, Biologically Relevant Transcriptomic Networks and Potential Utilization in Human Health Risk Assessment.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
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- Dose-response assessment of dipentyl phthalate effects on testosterone production and morphogenesis of late-gestation fetal rat testis.Environment international · 2025Article
- A workflow for human health hazard evaluation using transcriptomic data and Key Characteristics-based gene sets.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Modeling omics dose-response at the pathway level with DoseRider.Computational and structural biotechnology journal · 2025Article
- Bayesian gene set benchmark dose estimation for "omic" responses.Bioinformatics (Oxford, England) · 2024Article
- Assessment of pulmonary fibrosis using weighted gene co-expression network analysis.Frontiers in toxicology · 2024Article
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- Advancing the science of a read-across framework for evaluation of data-poor chemicals incorporating systematic and new approach methods.Regulatory toxicology and pharmacology : RTP · 2023Article
- 3' RNA-seq is superior to standard RNA-seq in cases of sparse data but inferior at identifying toxicity pathways in a model organism.Frontiers in bioinformatics · 2023Article
- Analyses of Transcriptomics Cell Signalling for Pre-Screening Applications in the Integrated Approach for Testing and Assessment of Non-Genotoxic Carcinogens.International journal of molecular sciences · 2022Review
- Advances in computational methods along the exposure to toxicological response paradigm.Toxicology and applied pharmacology · 2022Article
- Predicting molecular initiating events using chemical target annotations and gene expression.BioData mining · 2022Article
- ALOHA: Aggregated local extrema splines for high-throughput dose-response analysis.Computational toxicology (Amsterdam, Netherlands) · 2022Article
- Article
- High-Throughput Transcriptomics Platform for Screening Environmental Chemicals.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Unravelling actionable biology using transcriptomic data to integrate mitotic index and Ki-67 in the management of lung neuroendocrine tumors.Oncotarget · 2021Article
- Reproducibility and robustness of high-throughput S1500+ transcriptomics on primary rat hepatocytes for chemical-induced hepatotoxicity assessment.Current research in toxicology · 2021Article
- Transcriptomic analyses of livers from mice exposed to 1,4-dioxane for up to 90 days to assess potential mode(s) of action underlying liver tumor development.Current research in toxicology · 2021Article
- Deciphering the Protein, Modular Connections and Precision Medicine for Heart Failure With Preserved Ejection Fraction and Hypertension Based on TMT Quantitative Proteomics and Molecular Docking.Frontiers in physiology · 2021Article
- Transcriptomics in Toxicogenomics, Part II: Preprocessing and Differential Expression Analysis for High Quality Data.Nanomaterials (Basel, Switzerland) · 2020Review
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6 authors.
Funding
Abstract
The rate of new chemical development in commerce combined with a paucity of toxicity data for legacy chemicals presents a unique challenge for human health risk assessment. There is a clear need to develop new technologies and incorporate novel data streams to more efficiently inform derivation of toxicity values. One avenue of exploitation lies in the field of transcriptomics and the application of gene expression analysis to characterize biological responses to chemical exposures. In this context, gene set enrichment analysis (GSEA) was employed to evaluate tissue-specific, dose-response gene expression data generated following exposure to multiple chemicals for various durations. Patterns of transcriptional enrichment were evident across time and with increasing dose, and coordinated enrichment plausibly linked to the etiology of the biological responses was observed. GSEA was able to capture both transient and sustained transcriptional enrichment events facilitating differentiation between adaptive versus longer term molecular responses. When combined with benchmark dose (BMD) modeling of gene expression data from key drivers of biological enrichment, GSEA facilitated characterization of dose ranges required for enrichment of biologically relevant molecular signaling pathways, and promoted comparison of the activation dose ranges required for individual pathways. Median transcriptional BMD values were calculated for the most sensitive enriched pathway as well as the overall median BMD value for key gene members of significantly enriched pathways, and both were observed to be good estimates of the most sensitive apical endpoint BMD value. Together, these efforts support the application of GSEA to qualitative and quantitative human health risk assessment.
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