Kernel density weighted loess normalization improves the performance of detection within asymmetrical data

Background: Normalization of gene expression data has been studied for many years and various strategies have been formulated to deal with various types of data. Most normalization algorithms rely on the assumption that the number of up-regulated genes and the number of down-regulated genes are roughly the same. However, the well-known Golden Spike experiment presents a unique situation in which differentially regulated genes are biased toward one direction, thereby challenging the conclusions of previous bench mark studies. Results: This study proposes two novel approaches, KDL and KDQ, based on kernel density estimation to improve upon the basic idea of invariant set selection. The key concept is to provide various importance scores to data points on the MA plot according to their proximity to the cluster of the null genes under the assumption that null genes are more densely distributed than those that are differentially regulated. The comparison is demonstrated in the Golden Spike experiment as well as with simulation data using the ROC curves and compression rates. KDL and KDQ in combination with GCRMA provided the best performance among all approaches. Conclusions: This study determined that methods based on invariant sets are better able to resolve the problem of asymmetry. Normalization, either before or after expression summary for probesets, improves performance to a similar degree.