Discovery of pharmaceutically-targetable pathways and prediction of survivorship for pneumonia and sepsis patients from the view point of ensemble gene noise

Tristan de Jong; Victor Guryev; Yury M. Moshkin

Upon calling significantly changed genes, to make biological sense, these genes are mapped to known biological pathways, such as GO or KEGG [21, 22] , or to subunits of protein complexes annotated by CORUM or other interaction databases [23] . Thus, a second statistical test is required, namely gene set enrichment analysis (GSEA). However, this is not without its own caveats. The major one is that GSEA depends on the statistical inference of DGE and DGE cut-offs [24, 25] . As a result, biological interpretations from DGE might be drastically affected by pitfalls arising from the fluctuation-response relationship, DGE thresholding and the choice of statistical approach for GSEA.