Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Hannover, Germany.
Res Synth Methods. 2019 Mar;10(1):99-112. doi: 10.1002/jrsm.1337. Epub 2019 Feb 7.
Research synthesis, eg, by meta-analysis, is more and more considered in the area of high-dimensional data from molecular research such as gene and protein expression data, especially because most studies and experiments are performed with very small sample sizes. In contrast to most clinical and epidemiological trials, raw data are often available for high-dimensional expression data. Therefore, direct data merging followed by a joint analysis of selected studies can be an alternative to meta-analysis by P value or effect-size merging or, more generally spoken, the merging of results. While several methods for meta-analysis of differential expression studies have been proposed, meta-analysis of gene set tests has very rarely been considered, although gene set tests are standard in the analysis of individual gene expression studies. We compare in this work the different strategies of research synthesis of gene set tests, in particularly the "early merging" of data cleaned from batch effects versus the "late merging" of individual results. In simulation studies and in examples of manipulated real-world data, we found that in most scenarios, the early merging has a higher sensitivity of detecting a gene set enrichment than the late merging. However, in scenarios with few studies, large batch effect, moderate and large sample sizes of late merging are more sensitive than early merging.
研究综合，例如荟萃分析，在分子研究领域（如基因和蛋白质表达数据）的高维数据中越来越受到重视，尤其是因为大多数研究和实验都是用非常小的样本量进行的。与大多数临床和流行病学试验不同，高维表达数据通常可以获得原始数据。因此，直接进行数据合并，然后对选定的研究进行联合分析，可以替代基于 P 值或效应大小合并的荟萃分析，或者更广泛地说，可以替代结果的合并。虽然已经提出了几种用于差异表达研究荟萃分析的方法，但很少考虑基因集检验的荟萃分析，尽管基因集检验是分析单个基因表达研究的标准方法。在这项工作中，我们比较了基因集检验研究综合的不同策略，特别是从批次效应中清理数据的“早期合并”与个体结果的“晚期合并”。在模拟研究和人为操纵的真实世界数据的示例中，我们发现，在大多数情况下，早期合并比晚期合并具有更高的检测基因集富集的灵敏度。然而，在研究数量较少、批次效应较大、晚期合并样本量适中且较大的情况下，早期合并比晚期合并更敏感。
