Incorporating regulatory interactions into gene-set analyses for GWAS data: A controlled analysis with the MAGMA tool
Fig 7
The IRED procedure for identifying robust gains from augmentation for gene sets.
Genes were iteratively and cumulatively removed, one-by-one, from a selected gene set (beginning with the top-gaining gene, then the second-biggest gaining gene, and so forth). At each iteration, the impact on the gain of the gene set itself was inspected. One dot is shown for each iteration. Each dot represents the gene-set score difference (determined following probit transformations of one minus each FDR-adjusted, upper-tail p-value) in relation to the difference in the gene score (as used in gene-set analysis and for ranking the genes for IRED, before multiple-testing correction) of the top-gaining gene still present at an iteration. Given the nature of the procedure, progressive iterations are traced by moving from right to left on a graph. For clarity, red dots mean that the gene set demonstrates a gain from augmentation (otherwise, dots are black). The number of iterations for a gain to be lost for the first time (that is, the number of red dots before the first black dot is encountered when moving from right to left), is counted to assess robustness of a gain of a gene set. For both graphs, some top-gaining genes have been labelled for reference. (A) A robust gain (actin-mediated cell contraction gene set detected for atrial fibrillation with augmentation from the EPM of JEME dataset of regulatory interactions). (B) A non-robust gain (positive T-cell selection gene set detected for Crohn’s disease with augmentation from the EPM of PsychENCODE dataset of regulatory interactions).