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

本研究项目的目标是开发一种高维数据挖掘的方法，并将其应用于药物构效关系的分析，发现具有SNPs的医疗保健重要基因，以及寻找影响患者生活质量的必要因素。为了完成这项研究，进行了各种实验，包括使用DNA微阵列的湿法实验室工作。到目前为止所取得的一些成果如下：1.根据药物的化学结构开发了属性生成系统，以给出许多线性片段。扩展了Okada提出的级联模型，将规则组织成主规则和关联规则。3.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的药效团。4.胰岛素抵抗糖尿病患者的基因芯片实验获得了相关的SNPs。此外，还发现了与运动刺激、幽门螺杆菌和维甲酸相关的重要基因。5.开发了SNPs在受体-配体相互作用和转录到RNA中的作用的软件。6.收集医院老年患者的临床记录，调查了他们的细胞色素P450基因SNPs。分析表明，药物相互作用对患者的生活质量具有重要意义。7.提出了一种挖掘数值关联规则并将其用于分类的方法。8.建立了指尖脉搏波的测量方法，为分析人类的心理状况提供了一种简便的方法。

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.