O'Hara Laura, O'Shaughnessy Peter J, Freeman Tom C, Smith Lee B
MRC Centre for Reproductive Health, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Midlothian, EH25 9RG, UK.
BMC Res Notes. 2018 Apr 24;11(1):252. doi: 10.1186/s13104-018-3365-y.
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.
类固醇激素负责控制广泛的生理过程，如发育、生长、繁殖、代谢和衰老。由于参与类固醇生成的酶、底物和产物种类繁多，且其组成反应存在区室化，因此这是一个难以可视化和记录的复杂过程。系统生物学的目标之一是定量描述涉及许多成分相互作用的复杂生物系统的行为。这可以通过在途径模型中直观地表示这些相互作用，然后选择性地构建相互作用的数学模型来实现。
我们使用改进的爱丁堡途径表示法构建了一个描述人类类固醇生成途径的框架图，这将对内分泌学家有用。为了进一步展示其效用，我们展示了如何在Graphia Professional软件中用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，以及模拟基因敲除。这些框架模型支持在计算机上生成假设并进行跨内分泌终点的效用测试，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。
