BMC Bioinformatics. 2013;14 Suppl 16(Suppl 16):S13. doi: 10.1186/1471-2105-14-S16-S13. Epub 2013 Oct 22.
Identification of good metaphase spreads is an important step in chromosome analysis for identifying individuals with genetic disorders. The process of finding suitable metaphase chromosomes for accurate clinical analysis is, however, very time consuming since they are selected manually. The selection of suitable metaphase chromosome spreads thus represents a major bottleneck for conventional cytogenetic analysis. Although many algorithms have been developed for karyotyping, none have adequately addressed the critical bottleneck of selecting suitable chromosome spreads. In this paper, we present a software tool that uses a simple rule-based system to efficiently identify metaphase spreads suitable for karyotyping.
The chromosome shapes can be classified by the software into four main classes. The first and the second classes refer to individual chromosomes with straight and skewed shapes, respectively. The third class is characterized as those chromosomes with overlapping bodies and the fourth class is for the non-chromosome objects. Good metaphase spreads should largely contain chromosomes of the first and the second classes, while the third class should be kept minimal. Several image parameters were examined and used for creating rule-based classification. The threshold value for each parameter is determined using a statistical model. We observed that the Gaussian model can represent the empirical probability density function of the parameters and, hence, the threshold value can be easily determined. The proposed rules can efficiently and accurately classify the individual chromosome with > 90% accuracy.
The software tool, termed MetaSel, was developed. Using the Gaussian-based rules, the tool can be used to quickly rank hundreds of chromosome spread images so as to assist cytogeneticists to perform karyotyping effectively. Furthermore, MetaSel offers an intuitive, yet comprehensive, workflow to assist karyotyping, including tools for editing chromosome (split, merge and fix) and a karyotyping editor (moving, rotating, and pairing homologous chromosomes). The program can be freely downloaded from "http://www4a.biotec.or.th/GI/tools/metasel".
在识别个体遗传疾病的染色体分析中，鉴定良好的中期分裂相是一个重要步骤。然而，由于需要手动选择，寻找适合准确临床分析的中期染色体是一个非常耗时的过程。因此，选择合适的中期染色体分裂相是常规细胞遗传学分析的主要瓶颈。尽管已经开发了许多用于核型分析的算法，但没有一个算法能够充分解决选择合适染色体分裂相的关键瓶颈问题。在本文中，我们提出了一种使用简单基于规则的系统来有效地识别适合核型分析的中期分裂相的软件工具。
该软件可以将染色体形状分为四类。第一类和第二类分别指具有直线和倾斜形状的单个染色体。第三类的特征是具有重叠体的染色体，第四类是用于非染色体对象的染色体。良好的中期分裂相应该主要包含第一类和第二类的染色体，而第三类应尽可能少。检查了几个图像参数并用于创建基于规则的分类。使用统计模型确定每个参数的阈值。我们观察到，高斯模型可以表示参数的经验概率密度函数，因此可以很容易地确定阈值。所提出的规则可以以超过 90%的准确率有效地、准确地对单个染色体进行分类。
开发了一个名为 MetaSel 的软件工具。该工具使用基于高斯的规则，可以快速对数百张染色体分裂相图像进行排序，以协助细胞遗传学家有效地进行核型分析。此外，MetaSel 提供了一个直观而全面的工作流程，以协助核型分析，包括编辑染色体（分裂、合并和固定）的工具和核型编辑器（移动、旋转和配对同源染色体）。该程序可从"http://www4a.biotec.or.th/GI/tools/metasel"免费下载。
