A new method to study the change of miRNA-mRNA interactions due to environmental exposures.
A new method to study the change of miRNA-mRNA interactions due to environmental exposures.
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DOI：
10.1093/bioinformatics/btx256
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发表时间：
2017-07-15
期刊：
影响因子：
--
通讯作者：
Wang P
中科院分区：
文献类型：
--
作者：
Petralia F;Aushev VN;Gopalakrishnan K;Kappil M;W Khin N;Chen J;Teitelbaum SL;Wang P
表征不同类型的生物分子之间的相互作用的综合方法已被证明是有用的，以揭示信息的生物学机制。一个这样的例子是microRNA（miRNA）和信使RNA（mRNA）之间的相互作用，其失调可能对环境损伤敏感，导致表型改变。这项工作的目标是开发一种有效的数据集成方法来表征由于环境毒物暴露导致的miRNA和mRNA之间的失调。我们将使用动物实验的数据，旨在探讨低剂量的环境化学品暴露对大鼠正常乳腺发育的影响，以激励和评估所提出的方法。我们提出了一种新的网络方法-整合联合随机森林（iJRF），它使用网络模型来表征miRNAs和mRNAs之间的调控系统。iJRF被设计为在高维低样本量制度下工作，并且可以在不同的治疗条件下借用信息，以实现更准确的网络推理。它还有效地考虑了现有数据库中miRNA-mRNA调控关系的先验信息。当iJRF应用于环境化学暴露研究的数据时，我们检测到一些重要的miRNA，它们在对照组中调节了大量mRNA，但在暴露组中没有，这表明由于化学暴露导致miRNA活性的破坏。使用乳腺癌人细胞系进一步验证了化学暴露对两种受影响的miRNA的影响。R软件包iJRF可在CRAN获得。 补充数据可在Bioinformatics在线获得。
Integrative approaches characterizing the interactions among different types of biological molecules have been demonstrated to be useful for revealing informative biological mechanisms. One such example is the interaction between microRNA (miRNA) and messenger RNA (mRNA), whose deregulation may be sensitive to environmental insult leading to altered phenotypes. The goal of this work is to develop an effective data integration method to characterize deregulation between miRNA and mRNA due to environmental toxicant exposures. We will use data from an animal experiment designed to investigate the effect of low-dose environmental chemical exposure on normal mammary gland development in rats to motivate and evaluate the proposed method. We propose a new network approach—integrative Joint Random Forest (iJRF), which characterizes the regulatory system between miRNAs and mRNAs using a network model. iJRF is designed to work under the high-dimension low-sample-size regime, and can borrow information across different treatment conditions to achieve more accurate network inference. It also effectively takes into account prior information of miRNA–mRNA regulatory relationships from existing databases. When iJRF is applied to the data from the environmental chemical exposure study, we detected a few important miRNAs that regulated a large number of mRNAs in the control group but not in the exposed groups, suggesting the disruption of miRNA activity due to chemical exposure. Effects of chemical exposure on two affected miRNAs were further validated using breast cancer human cell lines. R package iJRF is available at CRAN. Supplementary data are available at Bioinformatics online.
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影响因子：
16.6
作者：
Ebrahim, Ali;Brunk, Elizabeth;Tan, Justin;O'Brien, Edward J.;Kim, Donghyuk;Szubin, Richard;Lerman, Joshua A.;Lechner, Anna;Sastry, Anand;Bordbar, Aarash;Feist, Adam M.;Palsson, Bernhard O.
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DOI：
10.1073/pnas.0508647102
发表时间：
2005-11-29
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
4.5
作者：
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通讯作者：
Lund, Anders H.
影响因子：
11.2
作者：
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通讯作者：
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