BPscore: An Effective Metric for Meaningful Comparisons of Structural Chromosome Segmentations.

Abstract

Studying the three-dimensional structure of chromosomes is an emerging field flourishing in recent years because of rapid development of experimental approaches for studying chromosomal contacts. This has led to numerous studies providing results of segmentation of chromosome sequences of different species into so-called topologically associating domains (TADs). As the number of such studies grows steadily and many of them make claims about the perceived differences between TAD structures observed in different conditions, there is a growing need for good measures of similarity (or dissimilarity) between such segmentations. We provide here a bipartite (BP) score, which is a relatively simple distance metric based on the bipartite matching between two segmentations. In this article, we provide the rationale behind choosing specifically this function and show its results on several different data sets, both simulated and experimental. We show that not only the BP score is a proper metric satisfying the triangle inequality, but also that it is providing good granularity of scores for typical situations occurring between different TAD segmentations. We also introduce local variant of the BP metric and show that in actual comparisons between experimental data sets, the local BP score is correlating with the observed changes in gene expression and genome methylation. In summary, we consider the BP score a good foundation for analyzing the dynamics of chromosome structures. The methodology we present in this study could be used by many researchers in their ongoing analyses, making it a popular and useful tool.