Image analysis for structural genomics

Abstract

Major success has been achieved in recent years in understanding the function of the genome. It has also become evident that the structure and organization of the genome in the nucleus is important. It changes along the cell cycle and during cancer progression. For structural and organizational studies to take place, it is necessary to apply markers and probe regions of interest (wetware) and to acquire images (hardware), tasks that have reached a mature state. For successful interpretation, a last step has to be made: analysis of the images (software). To obtain quantitative results, the first two components (wetware and hardware) have to be taken into account in the software and algorithms. To study the spatial organization of certain markers in the cell nucleus, e.g. telomeres and centromeres, we have developed an open source tool in the MatLab programming environment: TeloView. This tool can do automatic segmentation and localization of the markers of interest. After an interactive correction of this localization (if desired), we can perform several measurements and analysis on these markers (e.g. 3D position, size, intensity). We have used TeloView to study telomeres during the cell cycle of normal mammalian cells and after c-Myc deregulation. Centromeres have been studied in normal, senescent and apoptotic human mesenchymal stem cells. We will present the algorithms that were developed and some of the results. Novel biological processes have been discovered including the cell-cycle dependence of the telomeres, telomere aggregates during tumor progression, and the redistribution of centromeres during apoptosis.

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