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Transcript
Gene Set Enrichment Analysis GSEA: Key Features • Ranks all genes on array based on their differential expression • Identifies gene sets whose member genes are clustered either towards top or bottom of the ranked list (i.e. up- or down regulated) • Enrichment score calculated for each category • Permutation test to identify significantly enriched categories • Extensive gene sets provided via MolSig DB – GO, chromosome location, KEGG pathways, transcription factor or microRNA target genes GSEA Disease Control • Each gene category tested by traversing ranked list • Enrichment score starts at 0, weighted increment when a member gene encountered, weighted decrement otherwise Most significantly up-regulated genes Unchanged genes • Enrichment score – point where most different from zero Most significantly down-regulated genes Enrichment Score • Enrichment Score (ES) is calculated by evaluating the fractions of genes in S (‘‘hits’’) weighted by their correlation and the fractions of genes not in S (‘‘misses’’) present up to a given position i in the ranked gene list, L, where N genes are ordered according to the correlation, 4 GSEA algorithm GSEA: Permutation Test • Randomise data (groups), rank genes again and repeat test 1000 times • Null distribution of 1000 ES for geneset Null distribution of enrichment scores Actual ES • FDR q-value computed – corrected for gene set size and testing multiple gene sets
