Academic Journal
Elucidating disease-associated mechanisms triggered by pollutants via the epigenetic landscape using large-scale ChIP-Seq data
| العنوان: | Elucidating disease-associated mechanisms triggered by pollutants via the epigenetic landscape using large-scale ChIP-Seq data |
|---|---|
| المؤلفون: | Zou, Zhaonan, Yoshimura, Yuka, Yamanishi, Yoshihiro, Oki, Shinya |
| المساهمون: | 鄒, 兆南, 吉村, 侑花, 山西, 芳裕, 沖, 真弥, 90452713 |
| بيانات النشر: | Springer Nature BMC |
| سنة النشر: | 2023 |
| المجموعة: | Kyoto University Research Information Repository (KURENAI) / 京都大学学術情報リポジトリ |
| مصطلحات موضوعية: | ChIP-Seq, ATAC-seq, Transcription factor, Differentially accessible genomic region, Epigenetic landscape, Action modes of environmental pollutants |
| الوصف: | [Background] Despite well-documented effects on human health, the action modes of environmental pollutants are incompletely understood. Although transcriptome-based approaches are widely used to predict associations between chemicals and disorders, the molecular cues regulating pollutant-derived gene expression changes remain unclear. Therefore, we developed a data-mining approach, termed “DAR-ChIPEA, ” to identify transcription factors (TFs) playing pivotal roles in the action modes of pollutants. [Methods] Large-scale public ChIP-Seq data (human, n = 15, 155; mouse, n = 13, 156) were used to predict TFs that are enriched in the pollutant-induced differentially accessible genomic regions (DARs) obtained from epigenome analyses (ATAC-Seq). The resultant pollutant–TF matrices were then cross-referenced to a repository of TF–disorder associations to account for pollutant modes of action. We subsequently evaluated the performance of the proposed method using a chemical perturbation data set to compare the outputs of the DAR-ChIPEA and our previously developed differentially expressed gene (DEG)-ChIPEA methods using pollutant-induced DEGs as input. We then adopted the proposed method to predict disease-associated mechanisms triggered by pollutants. [Results] The proposed approach outperformed other methods using the area under the receiver operating characteristic curve score. The mean score of the proposed DAR-ChIPEA was significantly higher than that of our previously described DEG-ChIPEA (0.7287 vs. 0.7060; Q = 5.278 × 10⁻⁴²; two-tailed Wilcoxon rank-sum test). The proposed approach further predicted TF-driven modes of action upon pollutant exposure, indicating that (1) TFs regulating Th1/2 cell homeostasis are integral in the pathophysiology of tributyltin-induced allergic disorders; (2) fine particulates (PM2.5) inhibit the binding of C/EBPs, Rela, and Spi1 to the genome, thereby perturbing normal blood cell differentiation and leading to immune dysfunction; and (3) lead induces fatty liver by disrupting the ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1756-8935 |
| Relation: | http://hdl.handle.net/2433/286952; Epigenetics & Chromatin; 16; 34 |
| الاتاحة: | http://hdl.handle.net/2433/286952 |
| Rights: | © The Author(s) 2023. ; This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. ; http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.FBB954E |
| قاعدة البيانات: | BASE |
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