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ToxiTaRGET: a multi-omics resource for toxicant-responsive molecular targets
Ravindra Kumar1,2, Tianyi Fu1,2, Prashant Kumar Kuntala3
1Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63108, USA.
Abstract:
Environmental toxicant exposures can induce widespread alterations in both the transcriptome and epigenome of mammals, and directly contribute to the increased risk of various diseases, including cardiovascular disorders, cancer, and neurological disorders. To evaluate how early-life toxicants produce long-term impacts on the transcriptome and epigenome in mice, the Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription II (TaRGET II) Consortium generated a landmark resource comprising 3,607 multi-omics from longitudinal studies in mice. The molecular changes in responding to distinct environmental toxicants, including arsenic (As), lead (Pb), bisphenol A (BPA), tributyltin (TBT), di-2-ethylhexyl phthalate (DEHP), dioxin (TCDD), and fine particulate matter (PM2.5), were systematically identified and visualized on an integrative platform, ToxiTaRGET, to allow quickly search and browse by researchers. ToxiTaRGET houses a rich repository of molecular signatures, including gene expression, chromatin accessibility, and DNA methylation profiles, in response to early-life toxicant exposures. These molecular signatures span multiple biologically important tissues in both male and female mice at three distinct life stages, offering a valuable resource for the environmental health and toxicogenomic research communities.
Insights
Early-life exposure to environmental toxicants like arsenic and lead can cause lasting molecular changes in mice. The ToxiTaRGET II Consortium created a resource to study these toxicant-induced genomic and epigenomic alterations.
Area of Science:
- Environmental health
- Toxicogenomics
- Genomics and epigenomics
Background:
- Environmental toxicants induce molecular alterations, increasing disease risk.
- Understanding long-term impacts of early-life exposures is crucial.
Purpose of the Study:
- To evaluate long-term transcriptome and epigenome impacts of early-life toxicant exposures in mice.
- To create a comprehensive resource for studying these effects.
Main Methods:
- The Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription II (TaRGET II) Consortium conducted longitudinal studies.
- Generated 3,607 multi-omics datasets from mice exposed to various toxicants.
- Systematically identified and visualized molecular changes using the ToxiTaRGET platform.
Main Results:
- Identified molecular signatures (gene expression, chromatin accessibility, DNA methylation) in response to toxicants.
- Data spans multiple tissues, sexes, and life stages in mice.
- The ToxiTaRGET platform provides an integrated view of these molecular changes.
Conclusions:
- Early-life toxicant exposures cause significant and lasting molecular changes.
- The ToxiTaRGET resource facilitates research in environmental health and toxicogenomics.
- Provides a foundation for understanding disease links to environmental exposures.
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