Modelling steroidogenesis: a framework model to support hypothesis generation and testing across endocrine studies.
Modelling steroidogenesis: a framework model to support hypothesis generation and testing across endocrine studies.
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DOI：
10.1186/s13104-018-3365-y
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发表时间：
2018-04-24
影响因子：
1.8
通讯作者：
Smith LB
中科院分区：
文献类型：
--
作者：
O'Hara L;O'Shaughnessy PJ;Freeman TC;Smith LB
类固醇激素负责控制广泛的生理过程，如发育、生长、生殖、新陈代谢和衰老。由于参与类固醇合成的酶、底物和产物多种多样，其组成反应的区隔，使其可视化和记录是一个复杂的过程。系统生物学的目标之一是定量描述涉及许多组件相互作用的复杂生物系统的行为。这可以通过在路径模型中可视地表示这些交互作用，然后可选地构建交互作用的数学模型来实现。我们已经使用改进的爱丁堡路径记法构建了描述人类类固醇合成途径的框架图，这将对内分泌学家有用。为了展示进一步的实用性，我们展示了如何使用软件Graphia Professional中的经验数据对这些模型进行参数化，以概括类固醇激素产生的具体例子，并模拟基因敲除。这些框架模型支持跨内分泌终端的电子假说生成和测试，具有显著降低成本、时间和动物数量的潜力，同时为计划研究的设计提供信息。本文的在线版本(10.1186/s13104.0183365-y)包含补充材料，授权用户可以使用。
Steroid hormones are responsible for the control of a wide range of physiological processes such as development, growth, reproduction, metabolism, and aging. Because of the variety of enzymes, substrates and products that take part in steroidogenesis and the compartmentalisation of its constituent reactions, it is a complex process to visualise and document. One of the goals of systems biology is to quantitatively describe the behaviour of complex biological systems that involve the interaction of many components. This can be done by representing these interactions visually in a pathway model and then optionally constructing a mathematical model of the interactions. We have used the modified Edinburgh Pathway Notation to construct a framework diagram describing human steroidogenic pathways, which will be of use to endocrinologists. To demonstrate further utility, we show how such models can be parameterised with empirical data within the software Graphia Professional, to recapitulate specific examples of steroid hormone production, and also to mimic gene knockout. These framework models support in silico hypothesis generation and testing with utility across endocrine endpoints, with significant potential to reduce costs, time and animal numbers, whilst informing the design of planned studies. The online version of this article (10.1186/s13104-018-3365-y) contains supplementary material, which is available to authorized users.