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.

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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