Heterogenising study samples across testing time improves reproducibility of behavioural data
Heterogenising study samples across testing time improves reproducibility of behavioural data
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DOI：
10.1038/s41598-019-44705-2
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发表时间：
2019-06-03
影响因子：
4.6
通讯作者：
Richter, S. Helene
中科院分区：
文献类型：
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作者：
Bodden, Carina;von Kortzfleisch, Vanessa Tabea;Richter, S. Helene
关于生命科学中再现性危机的持续辩论突出了重新思考当前方法的必要性。由于越来越标准化的实验趋势有可能导致高度特异性的结果，因此提出了一种替代方法来提高发现的稳健性，特别是来自动物实验的发现。这个概念，被称为“系统的异质化”，假定增加外部有效性，因此，通过引入系统的变化到一个单一的实验，提高了再现性。然而，这一概念在实践中的实施需要确定合适的异质化因素。在这里，我们表明，在进行实验的一天中的时间有一个显着的影响，两个小鼠品系，C57 BL/6 J和DBA/2N之间的行为差异的再现性。具体来说，我们发现焦虑，探索和学习的显着不同的应变效果，这取决于测试时间，即上午，中午或下午。在后续的模拟方法中，我们证明了系统地包含两个不同的测试时间显着提高了重复实验之间的再现性。我们的研究结果强调了时间作为单实验室研究的有效且易于处理的异质化因素的潜力。它的系统变异可能提高研究结果的可重复性，因此有助于实验动物科学中实验设计和实施的基本问题。
The ongoing debate on the reproducibility crisis in the life sciences highlights the need for a rethinking of current methodologies. Since the trend towards ever more standardised experiments is at risk of causing highly idiosyncratic results, an alternative approach has been suggested to improve the robustness of findings, particularly from animal experiments. This concept, referred to as "systematic heterogenisation", postulates increased external validity and hence, improved reproducibility by introducing variation systematically into a single experiment. However, the implementation of this concept in practice requires the identification of suitable heterogenisation factors. Here we show that the time of day at which experiments are conducted has a significant impact on the reproducibility of behavioural differences between two mouse strains, C57BL/6J and DBA/2N. Specifically, we found remarkably varying strain effects on anxiety, exploration, and learning, depending on the testing time, i.e. morning, noon or afternoon. In a follow-up simulation approach, we demonstrate that the systematic inclusion of two different testing times significantly improved reproducibility between replicate experiments. Our results emphasise the potential of time as an effective and easy-to-handle heterogenisation factor for single-laboratory studies. Its systematic variation likely improves reproducibility of research findings and hence contributes to a fundamental issue of experimental design and conduct in laboratory animal science.