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Definition of GSEA

Gene Set Enrichment Analysis (Gene set enrichment Analysis) is used to evaluate the distribution trend of genes in a predefined gene set in the gene table sorted by phenotypic correlation, so as to determine its effect on phenotype. The input data consists of two parts, one is the gene set with known function (which can be GO annotation, MsigDB annotation or other gene set definition in accordance with the format), and the other is the expression matrix. The software sorts genes from large to small according to their phenotypic correlation (which can be understood as the change of expression value), and then determines whether each annotated gene in the gene set is enriched at the top or bottom of the gene table after phenotypic correlation ranking. In order to judge the effect of the synergistic change of genes in this gene set on the phenotypic change.

This is different from the GO enrichment analysis described earlier. GO enrichment analysis is to screen differential genes first, and then to determine which annotated pathways in which differential genes are enriched; this involves the setting of threshold, which is subjective and can only be used to express genes with large changes, that is, the significant differential genes we define. However, GSEA is not limited to differential genes. From the point of view of gene set enrichment, it is easier to include the effects of subtle but coordinated changes on biological processes in theory.

GSEA principle

Given a sequenced gene table L and a predefined gene set S (such as genes encoding a product of a metabolic pathway, genes with similar physical positions in the genome, or genes annotated by the same GO), the purpose of GSEA is to determine whether the members of S are randomly distributed in L or mainly gather at the top or bottom of L. The sequencing of these genes is based on their expression differences in different phenotypic states. if the members of the gene set S are significantly clustered at the top or bottom of L, it means that the members of this gene set contribute to the phenotypic differences. it's also the gene set we're concerned about.

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