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ToxiTaRGET:一个用于毒物反应性分子靶点的多组学资源库。

ToxiTaRGET: a multi-omics resource for toxicant-responsive molecular targets.

作者信息

Kumar Ravindra, Fu Tianyi, Kuntala Prashant Kumar, Miao Benpeng, Fu Shuhua, Li Daofeng, Bartolomei Marisa S, Walker Cheryl, Wang Ting, Zhang Bo A

机构信息

Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63108, USA.

Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63108, USA.

出版信息

bioRxiv. 2025 Jul 31:2025.07.28.667228. doi: 10.1101/2025.07.28.667228.

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.

摘要

环境毒物暴露可引起哺乳动物转录组和表观基因组的广泛改变,并直接导致包括心血管疾病、癌症和神经疾病在内的各种疾病风险增加。为了评估早期生活中的毒物如何对小鼠的转录组和表观基因组产生长期影响,毒物暴露与转录组和表观基因组调控因子的反应II(TaRGET II)联盟生成了一个具有里程碑意义的资源,其中包括来自小鼠纵向研究的3607个多组学数据。在一个综合平台ToxiTaRGET上,系统地识别并可视化了对不同环境毒物(包括砷(As)、铅(Pb)、双酚A(BPA)、三丁基锡(TBT)、邻苯二甲酸二(2-乙基己基)酯(DEHP)、二恶英(TCDD)和细颗粒物(PM2.5))作出反应的分子变化,以便研究人员快速搜索和浏览。ToxiTaRGET拥有丰富的分子特征库,包括基因表达、染色质可及性和DNA甲基化谱,以应对早期生活中的毒物暴露。这些分子特征跨越了雄性和雌性小鼠在三个不同生命阶段的多个具有生物学重要性的组织,为环境卫生和毒理基因组学研究群体提供了宝贵的资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee3e/12324349/4dc5bcf69446/nihpp-2025.07.28.667228v1-f0001.jpg

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