VSS: variance-stabilized signals for sequencing-based genomic signals

A sequencing-based genomic assay such as ChIP-seq outputs a real-valued signal for each position in the genome that measures the strength of activity at that position. Most genomic signals lack the property of variance stabilization. That is, a difference between 0 and 100 reads usually has a very different statistical importance from a difference between 1000 and 1100 reads. A statistical model such as a negative binomial distribution can account for this pattern, but learning these models is computationally challenging. Therefore, many applications-including imputation and segmentation and genome annotation (SAGA)-instead use Gaussian models and use a transformation such as log or inverse hyperbolic sine (asinh) to stabilize variance.