A Novel Joint Gene Set Analysis Framework Improves Identification of Enriched Pathways in Cross Disease Transcriptomic Analysis

Motivation: Gene set enrichment analysis is a widely accepted expression analysis tool which aims at detecting coordinated expression change within a pre-defined gene sets rather than individual genes. The benefit of gene set analysis over individual differentially expressed (DE) gene analysis includes more reproducible and interpretable results and detecting small but consistent change among gene set which could not be detected by DE gene analysis. There have been many successful gene set analysis applications in human diseases. However, when the sample size of a disease study is small and no other public data sets of the same disease are available, it will lead to lack of power to detect pathways of importance to the disease.

Results: We have developed a novel joint gene set analysis statistical framework which aims at improving the power of identifying enriched gene sets through integrating multiple similar disease data sets. Through comprehensive simulation studies, we demonstrated that our proposed frameworks obtained much better AUC scores than single data set analysis and another meta-analysis method in identification of enriched pathways. When applied to two real data sets, the proposed framework could retain the enriched gene sets identified by single data set analysis and exclusively obtained up to 200% more disease-related gene sets demonstrating the improved identification power through information shared between similar diseases. We expect that the proposed framework would enable researchers to better explore public data sets when the sample size of their study is limited.