Department of Physiology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
Institute of Computational Biomedicine, Faculty of Medicine, Heidelberg University, Germany.
FEBS Lett. 2020 Dec;594(24):4189-4200. doi: 10.1002/1873-3468.14011. Epub 2020 Dec 14.
Pathway analysis methods are frequently applied to cancer gene expression data to identify dysregulated pathways. These methods often infer pathway activity based on the expression of genes belonging to a given pathway, even though the proteins ultimately determine the activity of a given pathway. Furthermore, the association between gene expression levels and protein activities is not well-characterized. Here, we posit that pathway-based methods are effective not because of the correlation between expression and activity of members of a given pathway, but because pathway gene sets overlap with the genes regulated by transcription factors (TFs). Thus, pathway-based methods do not inform about the activity of the pathway of interest but rather reflect changes in TF activities.
通路分析方法常被应用于癌症基因表达数据，以识别失调的通路。这些方法通常基于给定通路中基因的表达来推断通路活性，尽管最终决定特定通路活性的是蛋白质。此外，基因表达水平与蛋白活性之间的关联尚未得到很好的描述。在这里，我们认为基于通路的方法之所以有效，不是因为给定通路成员的表达与活性之间存在相关性，而是因为通路基因集与转录因子（TFs）调控的基因重叠。因此，基于通路的方法并不能提供有关感兴趣通路活性的信息，而是反映了 TF 活性的变化。
