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

使用基于规则的数据挖掘来发现阿尔茨海默病的知识

• 批准号: 8360369
• 负责人: PRERNA SETHI
• 金额: $ 10.26万
• 依托单位: LOUISIANA STATE UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360369
• 关键词: Age; Alzheimer' s Disease; Amygdaloid structure; Biological Availability; Biomedical Research; Complex; Cytoplasm; DNA Microarray Chip; Data; Dependency; Development; Disease; Effectiveness; Funding; Future; Gene Cluster; Gene Expression; Gene Expression Regulation; Genes; Grant; Hippocampus (Brain); Human; I-kappa B Proteins; Inflammation; Information Theory; Knowledge Discovery; Louisiana; Methods; MicroRNAs; NF-kappa B; NFKBIA gene; National Center for Research Resources; Neurofibrillary Tangles; Pathway Analysis; Patients; Pattern; Physiological; Play; Principal Investigator; Regulation; Reporting; Research; Research Infrastructure; Resources; Role; Sampling; Senile Plaques; Source; Stress; Tissues; United States National Institutes of Health; Work; base; brain cell; cost; data mining; text searching; vector

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 阿尔茨海默病（AD）患者的杏仁核、海马体和扣带皮层显示出生理功能显着变化的迹象，伴随着淀粉样斑块和神经原纤维缠结，这是该病的标志。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 进展中起重要作用的共同调控的 miRNA 之间的生物学显着相关性非常重要。 NF-kappa-B 复合物受到 I-kappa-B 蛋白 (NFKBIA) 的抑制，该蛋白通过将 NF-kappa-B 捕获在细胞质中来使其失活。 MiRNA-146a（一种 NF-kappa-B 敏感基因）在受应激的人类脑细胞和 AD 中被发现含量增加，并且在炎症调节中发挥着至关重要的作用。在之前的工作中，观察到 miRNA-146a 似乎会降低 CFH 的量和生物利用度，促进脑细胞炎症并促进 AD 的发展。在本报告期内，我们通过使用信息论方法，特别集中于发现具有其他共同调节基因的歧视性 NF-κ-B 敏感模式，研究了患病和年龄匹配对照的 AD 海马组织的 DNA 微阵列基因表达数据。这种基于互信息（MI）的方法可以通过找到最具辨别力的基因向量来捕获基因之间的非线性依赖性。我们开发了一种基于团的方法，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同调节基因簇，这些基因簇显示出患病样本中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结果的有效性。我们未来的工作包括确定对照样品与 AD 样品中这些基因的调控并进行通路分析。