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Large-scale integration of microarray data: Investigating the pathologies of cancer and infectious diseases.

机译:微阵列数据的大规模整合:研究癌症和传染病的病理学。

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摘要

DNA microarray data provide a high-throughput technique for the genome-wide profiling of genes at the transcript level. With large amounts of microarray data deposited on various types and aspects of malignancies, microarray technology has revolutionized the study of cancer. Such experiments aid in the discovery of novel biomarkers and provide insight into disease diagnosis, prognosis and response to treatment. Nonetheless, microarray data contains non-biological obscuring variations and systemic biases, which can distort the extraction of true aberrations in gene expression. Moreover, the number of samples generated by a single experiment is typically less than is statistically required to support the large number of genes studied. As a result, biomarker gene lists produced from independent datasets show little overlap. Therefore, to understand the pathophysiology of cancers and the influence they exert on the cellular processes they override, methods for combining data from different sources are necessary.;Meta-analysis techniques have been utilized to address this issue by conducting an individual statistical analysis on each of the acquired datasets, then incorporating the results to generate a final gene list based on aggregated p-values or ranks. However, much of the publicly accessible cancer microarray datasets are unbalanced or asymmetric and therefore lack data from healthy samples. Consequently, critical and considerable amounts of data are overlooked. An integrative approach that combines data prior to analysis can incorporate asymmetric data. For this reason, a merge approach to the previously validated technique, the significance analysis of microarrays, is proposed. The merged SAM technique reproduced the known-cancer literature with higher coverage than meta-analysis in the five independent cancer tissues considered. The same methodology was extended to a database of approximately 6000 healthy and cancer samples arising from thirteen tissues. The integrative approach has allowed for the identification of key genes common to the invasive paths of multiple cancers and can aid in drug discovery. Moreover, this integrative microarray approach was applied to viral data from HIV-1, hepatitis C and influenza to investigate the effect of these infections on iron-binding proteins. Iron is crucial for proteins involved in metabolism, DNA synthesis and immunity, accentuating such proteins as direct or indirect viral targets.
机译:DNA微阵列数据提供了一种高通量技术,可用于在转录水平上对基因进行全基因组分析。随着大量的微阵列数据沉积在各种类型和各个方面的恶性肿瘤上,微阵列技术彻底改变了癌症的研究。这样的实验有助于发现新的生物标志物,并提供对疾病诊断,预后和对治疗的反应的见识。尽管如此,微阵列数据仍包含非生物学的模糊变化和系统性偏差,这可能会使基因表达中真实像差的提取失真。而且,由单个实验产生的样品数量通常少于支持大量研究基因的统计学所需数量。结果,由独立数据集产生的生物标志物基因列表几乎没有重叠。因此,为了了解癌症的病理生理学及其对它们所超越的细胞过程的影响,有必要组合来自不同来源的数据的方法。元分析技术已通过对每个肿瘤进行单独的统计分析来解决此问题。采集的数据集,然后合并结果以基于汇总的p值或等级生成最终的基因列表。但是,许多可公开获得的癌症微阵列数据集不平衡或不对称,因此缺乏健康样本的数据。因此,关键和大量数据被忽略了。在分析之前合并数据的集成方法可以合并非对称数据。因此,提出了一种对先前验证过的技术的合并方法,即微阵列的重要性分析。合并的SAM技术在五个独立的癌组织中以比荟萃分析更高的覆盖率再现了已知的癌症文献。相同的方法已扩展到由13个组织产生的大约6000个健康和癌症样本的数据库中。整合方法已允许鉴定多种癌症的侵入途径共有的关键基因,并有助于药物发现。此外,这种整合的微阵列方法已应用于HIV-1,丙型肝炎和流感的病毒数据,以研究这些感染对铁结合蛋白的影响。铁对于参与新陈代谢,DNA合成和免疫的蛋白质至关重要,可增强这类蛋白质作为直接或间接病毒靶标的能力。

著录项

  • 作者

    Dawany, Noor.;

  • 作者单位

    Drexel University.;

  • 授予单位 Drexel University.;
  • 学科 Engineering Biomedical.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 115 p.
  • 总页数 115
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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