利用染色中位数测定染色体区域的关联模式

Hu Ding, B. Stojković, R. Berezney, Jinhui Xu
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引用次数: 11

摘要

计算细胞核内染色体区域的准确和稳健的组织模式对于理解几个基本的基因组过程至关重要,例如基因激活的共同调节、基因沉默、X染色体失活和癌细胞中异常的染色体重排。先进的荧光标记和图像处理技术的使用使研究人员能够在大空间分辨率下研究染色体区域的相互作用。由此产生的大量数据需要高通量和自动化图像分析方法。在本文中,我们介绍了一种新的算法工具,用于研究细胞群体中染色体区域的关联模式。我们的方法以一组图形作为输入,每个细胞一个,包含有关染色体区域空间相互作用的信息,并产生一个包含整个种群基本信息的单个图形,并作为其结构代表。本文将这一组合问题表述为半定规划问题,并提出了有效求解该组合问题的新方法。我们在人工和真实的生物数据上验证了我们的方法,实验结果表明我们的方法产生了接近最优的解决方案,并且可以处理大型数据集,这是对现有技术的重大改进。
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Gauging Association Patterns of Chromosome Territories via Chromatic Median
Computing accurate and robust organizational patterns of chromosome territories inside the cell nucleus is critical for understanding several fundamental genomic processes, such as co-regulation of gene activation, gene silencing, X chromosome inactivation, and abnormal chromosome rearrangement in cancer cells. The usage of advanced fluorescence labeling and image processing techniques has enabled researchers to investigate interactions of chromosome territories at large spatial resolution. The resulting high volume of generated data demands for high-throughput and automated image analysis methods. In this paper, we introduce a novel algorithmic tool for investigating association patterns of chromosome territories in a population of cells. Our method takes as input a set of graphs, one for each cell, containing information about spatial interaction of chromosome territories, and yields a single graph that contains essential information for the whole population and stands as its structural representative. We formulate this combinatorial problem as a semi-definite programming and present novel techniques to efficiently solve it. We validate our approach on both artificial and real biological data, the experimental results suggest that our approach yields a near-optimal solution, and can handle large-size datasets, which are significant improvements over existing techniques.
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