Image Analysis of Gene Locus Positions Within Chromosome Territories in Human Lymphocytes

摘要

One of the important areas of current cellular research with substantial impacts on medicine is analyzing the spatial organization of genetic material within the cell nuclei. Higher-order chromatin structure has been shown to play essential roles in regulating fundamental cellular processes, like DNA transcription, replication, and repair. In this paper, we present an image analysis method for the localization of gene loci with regard to chromosomal territories they occupy in 3D confocal microscopy images. We show that the segmentation of the territories to obtain a precise position of the gene relative to a hard territory boundary may lead to undesirable bias in the results; instead, we propose an approach based on the evaluation of the relative chromatin density at the site of the gene loci. This method yields softer, fuzzier "boundaries", characterized by progressively decreasing chromatin density. The method therefore focuses on the extent to which the signals are located inside the territories, rather than a hard yes/no classification.