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ToxiTaRGET: a multi-omics database for toxicant-responsive molecular targets
Ravindra Kumar1,2, Tianyi Fu1,2, Prashant Kumar Kuntala3,4
1Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, 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 3607 multi-omics datasets 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, impacting gene expression and epigenomes. The ToxiTaRGET platform provides a comprehensive resource to study these toxicant-induced effects on health.
Area of Science:
- Environmental Health
- Toxicogenomics
- Genomics and Epigenomics
Background:
- Environmental toxicants induce significant transcriptome and epigenome alterations in mammals.
- These molecular changes are linked to increased risks of diseases such as cancer and cardiovascular disorders.
- Understanding long-term impacts of early-life toxicant exposure is crucial for environmental health research.
Purpose of the Study:
- To investigate the long-term effects of early-life toxicant exposures on the transcriptome and epigenome in mice.
- To create a comprehensive multi-omics dataset and an integrated platform for studying toxicant responses.
- To identify and visualize molecular changes induced by specific environmental toxicants.
Main Methods:
- The Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription II (TaRGET II) Consortium conducted longitudinal studies in mice.
- Generated 3607 multi-omics datasets, including gene expression, chromatin accessibility, and DNA methylation profiles.
- Systematically identified and visualized molecular changes using the integrative platform, ToxiTaRGET.
Main Results:
- Identified molecular signatures in response to diverse toxicants: arsenic (As), lead (Pb), bisphenol A (BPA), tributyltin (TBT), di-2-ethylhexyl phthalate (DEHP), dioxin (TCDD), and fine particulate matter (PM2.5).
- Molecular signatures were observed across multiple tissues in both male and female mice at three distinct life stages.
- The ToxiTaRGET platform provides easy access to these rich repositories of molecular data.
Conclusions:
- Early-life toxicant exposures induce widespread and persistent molecular alterations.
- The ToxiTaRGET resource offers valuable insights into the mechanisms of toxicant-induced diseases.
- This study provides a foundational resource for environmental health and toxicogenomic research.
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