Systems Toxicology: Real World Applications and Opportunities.
Systems Toxicology: Real World Applications and Opportunities.
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DOI：
10.1021/acs.chemrestox.7b00003
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发表时间：
2017-04-17
影响因子：
4.1
通讯作者：
Sturla SJ
中科院分区：
文献类型：
--
作者：
Hartung T;FitzGerald RE;Jennings P;Mirams GR;Peitsch MC;Rostami-Hodjegan A;Shah I;Wilks MF;Sturla SJ
系统毒理学旨在改变外源药物的不良生物效应如何从经验终点特征到描述作为不良结果途径和扰动网络的作用模式的基础。为了实现这一目标，系统毒理学需要整合体外和体内的毒性数据与计算模型。这种不断发展的方法主要取决于数据的可靠性和相关性，而数据的可靠性和相关性又取决于用于生成毒理学数据的实验模型和生物分析技术的质量。系统毒理学涉及大规模数据流（“大数据”）的使用，例如那些来自组学测量的数据，需要计算手段来获得信息结果。因此，综合分析多种分子测量，特别是通过组学策略获得的，是系统毒理学的关键方法。近年来，在体外测试系统和生物分析策略方面取得了重大进展，但一个前沿挑战是将观察到的网络扰动与表型联系起来，这将需要了解导致不良反应的途径和网络。2016年系统毒理学会议是在瑞士阿尔卑斯山举行的国际会议，该会议概述了在这一快速发展的领域中选择新兴应用的局限性和机遇。系统毒理学的目的是改变基础的不良生物效应的异种生物特征，从经验的终点到毒性的途径。这需要将体内和体外数据与计算建模相结合。测试系统和生物分析技术已经取得了重大进展，但确保数据的可靠性和相关性是一个持续关注的问题。新途径方法面临的主要挑战是确定如何将观察到的网络扰动与表型毒性联系起来。
Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized from empirical end points to describing modes of action as adverse outcome pathways and perturbed networks. Toward this aim, Systems Toxicology entails the integration of in vitro and in vivo toxicity data with computational modeling. This evolving approach depends critically on data reliability and relevance, which in turn depends on the quality of experimental models and bioanalysis techniques used to generate toxicological data. Systems Toxicology involves the use of large-scale data streams (“big data”), such as those derived from omics measurements that require computational means for obtaining informative results. Thus, integrative analysis of multiple molecular measurements, particularly acquired by omics strategies, is a key approach in Systems Toxicology. In recent years, there have been significant advances centered on in vitro test systems and bioanalytical strategies, yet a frontier challenge concerns linking observed network perturbations to phenotypes, which will require understanding pathways and networks that give rise to adverse responses. This summary perspective from a 2016 Systems Toxicology meeting, an international conference held in the Alps of Switzerland, describes the limitations and opportunities of selected emerging applications in this rapidly advancing field. Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized, from empirical end points to pathways of toxicity. This requires the integration of in vitro and in vivo data with computational modeling. Test systems and bioanalytical technologies have made significant advances, but ensuring data reliability and relevance is an ongoing concern. The major challenge facing the new pathway approach is determining how to link observed network perturbations to phenotypic toxicity.