The poisson margin test for normalization-free significance analysis of NGS data

Abstract

The current methods for the determination of the statistical significance of peaks and regions in next generation sequencing (NGS) data require an explicit normalization step to compensate for (global or local) imbalances in the sizes of sequenced and mapped libraries. There are no canonical methods for performing such compensations; hence, a number of different procedures serving this goal in different ways can be found in the literature. Unfortunately, the normalization has a significant impact on the final results. Different methods yield very different numbers of detected "significant peaks" even in the simplest scenario of ChIP-Seq experiments that compare the enrichment in a single sam..