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首页> 外文学位 >Data Mining of Two Large Transcriptomic Data Sets that Utilize Drosophila as a Model System for the Study of Neurodegeneration due to Aging and Trauma
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Data Mining of Two Large Transcriptomic Data Sets that Utilize Drosophila as a Model System for the Study of Neurodegeneration due to Aging and Trauma

机译：利用果蝇作为模型系统研究衰老和创伤引起的神经退行性变的两个大型转录组数据集的数据挖掘

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摘要

Intermittent fasting (IF) has been shown to have a positive impact on aging Drosophila, which included promoting longevity, lowering neural aggregates and improving behavior and autophagy responses in middle-aged flies. In a separate traumatic brain injury (TBI) model, we determined that repetitive bouts of injury had long-term negative consequences to longevity and neural function. Understanding the impact that aging, diet and TBI exposure has on the cellular and molecular response of the CNS could identify the conserved mechanisms that influence aging and trauma responses in human and mammalian systems and the development of potential treatments or therapies. Using the recent advances in RNA sequencing, tissues from IF and TBI Drosophila models were used for the transcriptional analysis of genes and functional pathways influenced by aging, diet and injury. The work outlined in this proposal used bioinformatics techniques to analyze RNAsequencing data generated from adult tissues taken at different ages or exposed to IF and TBI treatment conditions. For aged and IF-treated mRNA profiles, we developed an analytical pipeline that examined fold and variance changes from replicates within individual tissue datasets. Tissue-specific expression changes to metabolic, behavioral and proteolytic pathways were identified and correlated with the progressive dysregulation of key phenotypes. Much of this work centered on the novel concept that age-dependent increase "transcriptional drift" variance was suppressed following IF-treatment, thus partly restoring more youthful expression and phenotypic profiles. Preliminary analysis of TBI RNA-seq datasets has identified both acute and delayed changes (fold) to molecular pathways involved with inflammatory responses, wound healing, DNA repair, histone modification, and chromatin remodeling responses following TBI exposure. Through this analysis, both studies have useful insights into some of the complex molecular mechanism that are impacted with age and following IF-treatment and TBI exposure. A consistent finding from both RNA-seq studies was the fold change in epigenetic pathway components. The implications are that data mining of multiple RNA-seq datasets can identify profound in vivo changes to key molecular mechanisms that are impacted by aging, diet and trauma.
机译：间歇性禁食（IF）已被证明对果蝇的衰老有积极影响，包括提高寿命，降低神经聚集，改善中年果蝇的行为和自噬反应。在一个单独的创伤性脑损伤（TBI）模型中，我们确定重复性损伤对长寿和神经功能具有长期负面影响。了解衰老，饮食和TBI暴露对中枢神经系统细胞和分子反应的影响，可以确定影响人类和哺乳动物系统中衰老和创伤反应的保守机制，以及潜在疗法或疗法的发展。利用RNA测序的最新进展，将IF和TBI果蝇模型的组织用于受衰老，饮食和伤害影响的基因和功能途径的转录分析。该提案中概述的工作使用生物信息学技术来分析从不同年龄或暴露于IF和TBI治疗条件下的成人组织产生的RNA测序数据。对于衰老和IF处理的mRNA谱，我们开发了一种分析流程，可检查单个组织数据集中重复数据的倍数和方差变化。鉴定到了代谢，行为和蛋白水解途径的组织特异性表达变化，并将其与关键表型的进行性失调相关。这项工作大部分集中在一个新概念上，即中频治疗后年龄依赖性增加的“转录漂移”方差得到抑制，从而部分恢复了更年轻的表达和表型特征。对TBI RNA-seq数据集的初步分析已经确定了与TBI接触后炎症反应，伤口愈合，DNA修复，组蛋白修饰和染色质重塑反应有关的分子途径的急性和延迟变化（倍数）。通过这一分析，两项研究都对一些受年龄，IF治疗和TBI暴露影响的复杂分子机制提供了有用的见识。两项RNA-seq研究的一致发现是表观遗传途径成分的倍数变化。这意味着多个RNA-seq数据集的数据挖掘可以识别出受衰老，饮食和创伤影响的关键分子机制的深刻体内变化。

著录项

  • 作者

    Zhang, Sharon X.;

  • 作者单位

    San Diego State University.;

  • 授予单位 San Diego State University.;
  • 学科 Information science.;Biology.;Medicine.
  • 学位 M.S.
  • 年度 2018
  • 页码 85 p.
  • 总页数 85
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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