RULE-BASED DATA MINING FOR KNOWLEDGE DISCOVERY IN ALZHEIMER'S DISEASE USING

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 阿尔茨海默病（AD）患者的杏仁核、海马和扣带皮质显示出伴随淀粉样蛋白斑块和神经元缠结的生理功能显著变化的迹象，淀粉样蛋白斑块和神经元缠结是该疾病的标志。转录后基因调控的很大一部分是由miRNA网络控制的，因此发现在AD进展中具有实质性作用的共调控miRNA之间的生物学显著相关性是重要的。NF-κ-B复合物被I-κ-B蛋白（NF KBIA）抑制，I-κ-B蛋白通过将NF-κ-B捕获在细胞质中而将其包裹。miRNA-146 a（一种NF-κ B敏感基因）在应激人脑细胞和AD中的含量增加，并且在炎症调节中起着至关重要的作用。在先前的工作中，观察到miRNA-146 a似乎降低了CFH的量和生物利用度，促进了脑细胞的炎症并有助于AD的发展。在本报告期间，我们研究了AD患者和年龄匹配对照组海马组织的DNA微阵列基因表达数据，具体集中于
使用信息论方法，用其他共调节基因来区分NF-κ B敏感模式。这种基于互信息（MI）的方法可以通过以下方式捕获基因之间的非线性依赖关系：
找出最具鉴别力的基因载体我们开发了一种基于基因组的方法，使用可变和固定阈值来保留显着的基因-基因相关性，从而识别数据中的共调节基因簇，这些基因簇在患病样本中显示出相同的变化趋势模式。我们进行了生物医学文献检索，以支持我们的结果的有效性。我们未来的工作包括确定这些基因在对照和AD样品中的调控，并进行通路分析。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The amygdala, hippocampus, and cingular cortex of Alzheimer disease (AD) patients show signs of significant changes in physiological function that accompany the amyloid plaques and neurofibrillary tangles that are hallmarks of the disease. A substantial portion of the post-transcriptional gene regulation is controlled by miRNA networks and hence it is important to discover the biologically significant correlations among co-regulated miRNAs that have a substantial role in the progression of AD. The NF-kappa-B complex is inhibited by I-kappa-B proteins (NFKBIA), which inactivate NF-kappa-B by trapping it in the cytoplasm. MiRNA-146a (an NF-kappa-B-sensitive gene) is found in increased amounts in stressed human brain cells and in AD, and that it plays a crucial role in the regulation of inflammation. In the previous work it was observed that miRNA-146a appears to reduce the amount and bioavailability of CFH, promoting the inflammation of brain cells and contributing to the development of AD. During this reporting period, we have investigated into the DNA microarray gene expression data from AD hippocampal tissue of diseased and age-matched controls by specifically concentrating to
nd discriminatory NF-kappa-B-sensitive patterns with other co-regulated genes using an information theory approach. This Mutual Information (MI) based approach can capture the non-linear dependencies amongst the genes by
nding the most discriminatory gene vector. We developed a clique-based method using variable and fixed thresholds to retain the significant gene-gene correlations and will consequently identify co-regulated gene clusters in the data that show the same pattern of changing tendencies in the diseased samples. We performed a biomedical literature search to support the effectiveness of our results. Our future work comprises in identifying the regulation of these genes in control versus the AD samples and carrying out the pathway analysis.