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当两组样本间基因表达的差异程度较低或样本量较少时,采用通常的错误发现率(falsediscovery rate,FDR)控制水平(如5%或10%),可能无法识别足够多的差异表达基因以进行后续的功能富集分析。然而,功能富集分析对差异表达基因中的错误发现具有一定的稳健性。所以,采用较低的FDR控制水平(即允许较高的FDR)识别差异表达基因,可能可以可靠地发现疾病相关功能。本文分析了5套研究乳腺癌转移的基因表达谱,通过其中差异表达信号较强的3套数据,论证了即使差异表达基因的FDR达到25%,功能富集分析的结果仍具有较高的稳健性。然后,在另外2套差异表达信号微弱的数据中,采用25%的FDR控制水平筛选差异表达基因来进行功能富集分析,并与前述3套数据的功能富集结果做比较。结果显示,采用较低的FDR控制水平筛选差异表达基因,仍然可以可靠地识别乳腺癌转移相关功能。分析结果也提示,在乳腺癌转移过程中,一些功能较为宽泛的生物学过程(如细胞分裂、细胞周期和DNA复制等)整体受到了扰动,反映出乳腺癌转移是一种涉及广泛基因表达改变的系统性疾病。
When the common error rate (eg, 5% or 10%) is controlled by falsediscovery rate (FDR) when there is a low level of gene expression difference between the two groups of samples or the sample size is small, sufficient differential expression may not be identified Genes for subsequent functional enrichment analysis. However, functional enrichment analysis has some robustness to false discoveries in differentially expressed genes. Therefore, using lower levels of FDR control (ie, allowing higher FDRs) to identify differentially expressed genes may make it possible to reliably detect disease-related functions. In this study, we analyzed five sets of gene expression profiles that were used to study metastasis of breast cancer, and demonstrated that even if the FDR of differentially expressed genes reaches 25%, three sets of data with strong differential signals show that the results of functional enrichment analysis are still robust Sex. Then, in the other two sets of data with weakly differentially expressed signals, the differentially expressed genes were screened by 25% FDR for functional enrichment analysis and compared with the results of the above three sets of data. The results show that screening for differentially expressed genes using lower FDR control levels can still reliably identify breast cancer metastasis-related functions. The results also suggest that some of the more broadly defined biological processes (such as cell division, cell cycle, and DNA replication) have been disturbed during breast cancer metastasis, reflecting the widespread involvement of breast cancer as a metastasis involving extensive gene expression changes Systemic disease.