Comparisons of a Gene Set Enrichment Analysis (GSEA) to a Multi-Species Meta-Analysis for Identification of Pathways Involved in Parasite Resistance in Sheep

Gene set enrichment analysis (GSEA) was compared to meta-analysis to determine relevant in pathways in parasite resistance in sheep. The use of the GSEA is widely accepted to determine common pathways associated with gene lists and to gain biological insight.  However, functional comparisons of genes in lists have been only marginally useful for the discovery of candidate genes.   Meta-analysis and GSEA were tested to determine the significances in pathways for parasite resistance genes. Data from QTL and gene expression studies were collected from published projects in sheep, cattle, mice, and human. Selected meta-analysis indexed pathways were compared to pathways identified through GSEA.  The comparisons indicated that neither GSEA or meta-analysis alone were very effective at determining pathways involved in parasite resistance.  However,  a combination of GSEA and meta-analysis may be a more useful method for identification of pathways.  One possible approach explored was using GSEA for the development of weights for genes in a meta-analysis approach.  Improved meta-analysis models will increase the discovery of candidate genes for economically important traits.