The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, Denmark; Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark; Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, Denmark; Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark; Department of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Old Age Psychiatry, Institute of Psychiatry, Psychology, & Neuroscience, King's College London, London, United Kingdom; Mental Health of Older Adults and Dementia Clinical Academic Group, South London and Maudsley NHS Foundation Trust, London, United Kingdom.
J Neurosci Methods. 2018 Feb 15;296:93-98. doi: 10.1016/j.jneumeth.2017.12.022. Epub 2017 Dec 26.
Dendritic spine morphology is heterogeneous and highly dynamic. To study the changing or aberrant morphology in test setups, often spines from several neurons from a few experimental units e.g. mice or primary neuronal cultures are measured. This strategy results in a multilevel data structure, which, when not properly addressed, has a high risk of producing false positive and false negative findings.
We used mixed-effects models to deal with data with a multilevel data structure and compared this method to analyses at each level. We apply these statistical tests to a dataset of dendritic spine morphology parameters to illustrate advantages of multilevel mixed-effects model, and disadvantages of other models.
We present an application of mixed-effects models for analyzing dendritic spine morphology datasets while correcting for the data structure.
We further show that analyses at spine level and aggregated levels do not adequately account for the data structure, and that they may lead to erroneous results.
We highlight the importance of data structure in dendritic spine morphology analyses and highly recommend the use of mixed-effects models or other appropriate statistical methods to deal with multilevel datasets. Mixed-effects models are easy to use and superior to commonly used methods by including the data structure and the addition of other explanatory variables, for example sex, and age, etc., as well as interactions between variables or between variables and level identifiers.
树突棘形态具有异质性和高度动态性。为了在测试方案中研究形态的变化或异常,通常会测量来自几个实验单位(例如小鼠或原代神经元培养物)的几个神经元的棘。这种策略会产生多层次的数据结构,如果处理不当,会有产生假阳性和假阴性结果的高风险。
我们使用混合效应模型来处理具有多层次数据结构的数据,并将这种方法与每个层次的分析进行比较。我们将这些统计检验应用于树突棘形态参数的数据集,以说明多层次混合效应模型的优势,以及其他模型的劣势。
我们提出了一种应用混合效应模型来分析树突棘形态数据集的方法,同时纠正数据结构。
我们进一步表明,棘水平和聚合水平的分析不能充分考虑数据结构,并且可能导致错误的结果。
我们强调了数据结构在树突棘形态分析中的重要性,并强烈建议使用混合效应模型或其他适当的统计方法来处理多层次数据集。混合效应模型易于使用,并且通过包含数据结构以及其他解释变量(例如性别和年龄等)以及变量之间或变量和级别标识符之间的交互,优于常用方法。