1,p-value计算方法
Estimating Significance. We assess the significance of an observed ES by comparing it with the set of scores ESNULL computed with randomly assigned phenotypes.
- Randomly assign the original phenotype labels to samples, reorder genes, and re-compute ES(S).
- Repeat step 1 for 1,000 permutations, and create a histogram of the corresponding enrichment scores ESNULL.
- Estimate nominal P value for S from ESNULL by using the positive or negative portion of the distribution corresponding to the sign of the observed ES(S).
2,FDR计算方法
Multiple Hypothesis Testing.
- Determine ES(S) for each gene set in the collection or database.
- For each S and 1000 fixed permutations π of the phenotype labels, reorder the genes in L and determine ES(S, π).
- Adjust for variation in gene set size. Normalize the ES(S, π) and the observed ES(S), separately rescal

文章介绍了评估观察到效果显著性的两种方法:一是通过比较观察到的效果大小(ES)与随机分配表型后计算的ES_NULL分布来估计p值;二是通过多次固定表型标签的重排,调整基因集大小,计算FDR,控制假阳性率,并利用NES(S,π)的分布计算FDRq值,以确定特定显著性水平的基因集。
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