The power of enrichment analysis for epigenetics: Application to schizophrenia
As regular readers of GenomeSpot will know, we have adopted the mitch package to enable enrichment analysis of methylation array data, as shown in our recent pre-print . You might be thinking that enrichment analysis of methylation data has existed for a long time, so why do we need a new approach? Well the answer to that is the current methods suffer one of the critical problems: (1) they use over-representation analysis (ORA), which has very low sensitivity, or (2) they do not distinguish between up- and down- directions of methylation change. (1) is a problem because ORA relies on binary classification of probes or genes into differential or not, whereas in reality probes and genes are spread on a distribution of differential-ness. This makes ORA easy to compute, but leads to low sensitivity. In serious cases, the (arbitrary) threshold used for selection of differential probes means that very few probes are present in the foreground. (2) is a problem because gene and pathways are t