Dept. Functional Genomics, CNCR, VU University Amsterdam, 1081 HV, Amsterdam, The Netherlands.
Functional Genomics, Department of Human Genetics, CNCR, Amsterdam, UMC, 1081 HV, Amsterdam, The Netherlands.
Mol Psychiatry. 2023 Apr;28(4):1545-1556. doi: 10.1038/s41380-022-01866-3. Epub 2022 Nov 16.
Studies using induced pluripotent stem cells (iPSCs) are gaining momentum in brain disorder modelling, but optimal study designs are poorly defined. Here, we compare commonly used designs and statistical analysis for different research aims. Furthermore, we generated immunocytochemical, electrophysiological, and proteomic data from iPSC-derived neurons of five healthy subjects, analysed data variation and conducted power simulations. These analyses show that published case-control iPSC studies are generally underpowered. Designs using isogenic iPSC lines typically have higher power than case-control designs, but generalization of conclusions is limited. We show that, for the realistic settings used in this study, a multiple isogenic pair design increases absolute power up to 60% or requires up to 5-fold fewer lines. A free web tool is presented to explore the power of different study designs, using any (pilot) data.
使用诱导多能干细胞（iPSC）的研究在脑疾病模型构建方面正在取得进展，但最佳研究设计的定义尚不清楚。在这里，我们比较了不同研究目的常用的设计和统计分析方法。此外，我们从五个健康个体的 iPSC 衍生神经元中生成了免疫细胞化学、电生理和蛋白质组学数据，分析了数据变异性并进行了功效模拟。这些分析表明，已发表的病例对照 iPSC 研究通常功效不足。使用同基因 iPSC 系的设计通常比病例对照设计具有更高的功效，但结论的推广受到限制。我们表明，对于本研究中使用的现实设置，多个同基因对设计可将绝对功效提高高达 60%，或最多减少 5 倍的细胞系数量。我们提供了一个免费的网络工具，可使用任何（初步）数据探索不同研究设计的功效。
