肺癌RNA-Seq数据中RNA编辑事件的识别算法和系统分析

发布时间：2018-05-06 19:48

本文选题：RNA-Seq + 肺癌　；参考：《苏州大学》2015年硕士论文

【摘要】：肺癌是发病率和死亡率增长速度最快的恶性肿瘤之一,当前关于肺癌的病理机制尚未完全清楚,分子生物学研究将有助于肺癌的早期诊断。RNA编辑是一种重要的转录后调控事件,对肿瘤的发生和发展、侵袭转移、化疗耐药以及预后等有着重要的调节作用。目前关于肺癌内RNA编辑机制的研究尚不完善,本文将基于庞大的RNA-Seq数据集合挖掘肺癌中RNA编辑事件,分析特异性RNA编辑位点的生物学功能。研究基于一套RNA编辑识别算法以精确定位肺癌中的RNA编辑位点,该算法涵盖模式识别中聚类分析算法、二项分布、T-test、BenjaminiHochberg多重校正等统计学方法。此外,算法通过排除单核苷酸多态性、癌突变、测序错误、简单重复序列和旁系同源序列等干扰性因素以降低候选位点集合中的假阳性。根据RNA编辑位点在癌与癌旁组织中的编辑水平差异,研究最终识别149个特异性编辑位点,其中位于CDS区的位点有11个,位于3’UTR区的位点有97个。在特异性RNA编辑与肺癌机制的相关性的系统研究中,存在9个编辑位点改变氨基酸序列,其中IGFBP7和AZIN1的编辑事件潜在地影响肺癌的生物学进程,位于3’UTR区的78个编辑位点破坏、新建、削弱或增强mi RNA与m RNA的靶向结合,其中多个mi RNA与肺癌的病理机制相关。从RNA编辑角度分析肺癌的病理机制,为寻找潜在的药物靶标作用点以及更好的肺癌诊断指标、预后指标以及治疗方法提供理论基础。
[Abstract]:Lung cancer is one of the most rapidly increasing morbidity and mortality of malignant tumors. The pathological mechanism of lung cancer is not fully understood. Molecular biology research will contribute to the early diagnosis of lung cancer. RNA editing is an important post-transcriptional regulation event. It plays an important role in tumorigenesis and development, invasion and metastasis, chemotherapeutic resistance and prognosis. At present, the research on the mechanism of RNA editing in lung cancer is not perfect. Based on the huge RNA-Seq data set, we will mine RNA editing events in lung cancer and analyze the biological functions of specific RNA editing sites. Based on a set of RNA editing and recognition algorithms to accurately locate RNA editing sites in lung cancer, this algorithm includes cluster analysis algorithm in pattern recognition, binomial distribution T-test Benjamini Hochberg multiple correction and other statistical methods. In addition, the algorithm reduces false positivity in candidate locus by excluding interference factors such as single nucleotide polymorphism, cancer mutation, sequencing error, simple repeat sequence and homologous sequence. According to the difference of editing level between cancer and paracancerous tissues, 149 specific editing sites were identified, of which 11 were located in the CDS region and 97 in the 3'UTR region. In the systematic study of the relationship between specific RNA editing and lung cancer mechanism, nine editing sites changed amino acid sequence. Among them, the editing events of IGFBP7 and AZIN1 potentially affected the biological process of lung cancer. 78 editing sites located in the 3'UTR region were destroyed, resulting in new, weakened or enhanced targeted binding of mi RNA to m RNA, many of which were related to the pathological mechanism of lung cancer. The pathological mechanism of lung cancer is analyzed from the point of view of RNA editing, which provides a theoretical basis for finding potential drug target sites and better diagnostic indicators, prognostic indicators and treatment methods for lung cancer.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R734.2

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