Mapping drug physico-chemical features to pathway activity reveals molecular networks linked to toxicity outcome.
Mapping drug physico-chemical features to pathway activity reveals molecular networks linked to toxicity outcome.
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DOI：
10.1371/journal.pone.0012385
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发表时间：
2010-08-27
期刊：
影响因子：
3.7
通讯作者：
Falciani F
中科院分区：
文献类型：
--
作者：
Antczak P;Ortega F;Chipman JK;Falciani F
预测性生物标志物的鉴定是现代毒理学的核心。到目前为止，已经提出了一些方法。这些依赖于从化合物特征（即，QSAR）、基于体外细胞的测定或靶组织的分子谱分析（即，表达谱分析）。虽然这些方法已经显示出预测毒理学的潜力，但我们仍然没有系统的方法来模拟化学特征，分子网络和毒性结果之间的相互作用。在这里，我们描述了一个计算策略，旨在解决这一重要的需求。其应用于肾小管变性模型揭示了物理化学特征和控制细胞通信途径的信号传导组分之间的联系，这些信号传导组分又在响应有毒化学物质时被差异调节。总体而言，我们的研究结果是一致的存在一个一般的毒性机制协同作用，更具体的单目标为基础的行动模式（MOAs），并提供了一个总体框架的发展综合方法预测毒理学。
The identification of predictive biomarkers is at the core of modern toxicology. So far, a number of approaches have been proposed. These rely on statistical inference of toxicity response from either compound features (i.e., QSAR), in vitro cell based assays or molecular profiling of target tissues (i.e., expression profiling). Although these approaches have already shown the potential of predictive toxicology, we still do not have a systematic approach to model the interaction between chemical features, molecular networks and toxicity outcome. Here, we describe a computational strategy designed to address this important need. Its application to a model of renal tubular degeneration has revealed a link between physico-chemical features and signalling components controlling cell communication pathways, which in turn are differentially modulated in response to toxic chemicals. Overall, our findings are consistent with the existence of a general toxicity mechanism operating in synergy with more specific single-target based mode of actions (MOAs) and provide a general framework for the development of an integrative approach to predictive toxicology.
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DOI：
10.1177/00359157770700s207
发表时间：
1977-01-01
期刊：
PROCEEDINGS OF THE ROYAL SOCIETY OF MEDICINE-LONDON
影响因子：
--
作者：
SCHOEPPE, W
通讯作者：
SCHOEPPE, W
影响因子：
3.1
作者：
Freeman, JW;DeArmond, D;Zhao, SJ
通讯作者：
Zhao, SJ
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
3
作者：
Song, Sarah;Black, Michael A.
通讯作者：
Black, Michael A.
影响因子：
6
作者：
Geng, Hui;Lan, Rongpei;Venkatachalam, Manjeri A.
通讯作者：
Venkatachalam, Manjeri A.