Zhao Hongya, Yan Hong
Department of Electronic Engineering, City University of Hong Kong, Kowloon, Hong Kong.
BMC Bioinformatics. 2007 Jul 17;8:256. doi: 10.1186/1471-2105-8-256.
Three-color microarray experiments can be performed to assess drug effects on the genomic scale. The methodology may be useful in shortening the cycle, reducing the cost, and improving the efficiency in drug discovery and development compared with the commonly used dual-color technology. A visualization tool, the hexaMplot, is able to show the interrelations of gene expressions in normal-disease-drug samples in three-color microarray data. However, it is not enough to assess the complicated drug therapeutic effects based on the plot alone. It is important to explore more effective tools so that a deeper insight into gene expression patterns can be gained with three-color microarrays.
Based on the celebrated Hough transform, a novel algorithm, HoughFeature, is proposed to extract line features in the hexaMplot corresponding to different drug effects. Drug therapy results can then be divided into a number of levels in relation to different groups of genes. We apply the framework to experimental microarray data to assess the complex effects of Rg1 (an extract of Chinese medicine) on Hcy-related HUVECs in details. Differentially expressed genes are classified into 15 functional groups corresponding to different levels of drug effects.
Our study shows that the HoughFeature algorithm can reveal natural cluster patterns in gene expression data of normal-disease-drug samples. It provides both qualitative and quantitative information about up- or down-regulated genes. The methodology can be employed to predict disease susceptibility in gene therapy and assess drug effects on the disease based on three-color microarray data.
可以进行三色微阵列实验以在基因组规模上评估药物效果。与常用的双色技术相比,该方法在缩短药物发现和开发周期、降低成本以及提高效率方面可能是有用的。一种可视化工具——六重图(hexaMplot),能够展示三色微阵列数据中正常-疾病-药物样本中基因表达的相互关系。然而,仅基于该图来评估复杂的药物治疗效果是不够的。探索更有效的工具很重要,以便通过三色微阵列更深入地了解基因表达模式。
基于著名的霍夫变换,提出了一种新颖的算法——霍夫特征(HoughFeature),用于在六重图中提取与不同药物效果相对应的线条特征。然后可以根据不同的基因组将药物治疗结果分为多个水平。我们将该框架应用于实验微阵列数据,以详细评估人参皂苷Rg1(一种中药提取物)对同型半胱氨酸相关人脐静脉内皮细胞(Hcy-related HUVECs)的复杂影响。差异表达基因被分为15个功能组,对应于不同水平的药物效果。
我们的研究表明,霍夫特征算法可以揭示正常-疾病-药物样本基因表达数据中的自然聚类模式。它提供了关于上调或下调基因的定性和定量信息。该方法可用于预测基因治疗中的疾病易感性,并基于三色微阵列数据评估药物对疾病的影响。