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Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
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Studies that assess how a drug is absorbed, distributed, metabolized, and excreted (ADME) at toxic doses are termed toxicokinetics. Understanding toxicokinetics helps predict adverse drug reactions (ADRs) and manage toxicity in humans.Toxicokinetics differs from pharmacokinetics mainly in the dose levels studied, with toxicokinetics focusing on higher toxic doses. The kinetics at these levels can be non-linear due to altered physiological processes. Toxicodynamics examines the relationship...
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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.

Nature Communications
|May 28, 2026
PubMed
Summary
This summary is machine-generated.

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.

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Published on: March 14, 2019

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.