High dimensional data mining of drug therapeutic effects by the analysis of single nucleotide polymorphism and chemical structure of drugs

本研究计划的目标是发展一种高维数据的数据挖掘方法，并将其应用于药物的构效关系分析，发现具有医疗保健snp的重要基因，以及发现影响患者生活质量的关键因素。为了完成研究，进行了各种实验，包括使用DNA微阵列的湿实验室工作。迄今取得的几项成果如下：1。从药物的化学结构出发，开发了属性生成系统，给出了许多线性片段。为了实现有效、高效的挖掘，还引入了属性选择方案。将Okada开发的一种挖掘方法级联模型进行扩展，将规则组织为主规则和相对规则。为了更好地理解数据环境，还引入了规则的地形表示。将上述方法应用于多巴胺受体配体，发现了激动剂和拮抗剂药物载体。胰岛素抵抗型糖尿病患者的微阵列实验鉴定出相关的snp。此外，还发现了运动刺激、幽门螺杆菌和维甲酸等可诱发癌症的重要基因。已经开发了软件来评估snp在受体-配体相互作用和转录到rna中的作用。收集医院老年人的临床记录，并对其CYP450 snp进行调查。分析表明，药物相互作用对患者的生活质量很重要。提出了一种挖掘数字关联规则并将其用于分类的方法。指尖脉搏波测量是一种简便易行的分析人体心理状态的方法。

The objectives of this research project are to develop a methodology of data mining for high dimensional data, and to apply it to the analysis of structure-activity relationships of drugs, the discovery of important genes with SNPs for medical care as well as finding essential factors influencing the quality of patients' life. Various experiments are done to accomplish the research, including wet lab works using DNA microarray. Several results achieved to date are shown below.1.Attribute generation system from the chemical structure of drugs is developed to give many linear fragments. The attribute selecting scheme is also introduced to facilitate the effective and efficient mining.2.The cascade model, a mining method developed by Okada, was extended to organize rules into principal and relative rules. Topographical expression of rules was also introduced to provide the better understanding of datascape.3.The application of the above method to Dopamine receptor ligands resulted in the discovery of agonist and antagonist pharmacophores.4.Microarray experiments of insulin-resistant diabetic patients led to the identification relevant SNPs. Further, important genes were discovered, which are evoked by locomotor stimulation, Helicobacter pylori and retinoic acid used to prevent cancer.5.Software has been developed to evaluate SNPs effects in receptor-ligand interaction and transcription to RNA.6.Clinical records in the hospital for the old are collected and their CYP450 SNPs were investigated. The analysis has shown that pharmaceutical interactions are important for the patients' quality of life.7.A method was developed to mine numerical association rules and to utilize them for the classification.8.Measurement of fingertip pulse waves was established as a simple and convenient method to analyze the human's psychological conditions.