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標題: | 探討糖尿病人腸胃細菌對於血糖血脂調控之關聯性 Investigate the Association Between Microbiomeand Blood Glucose and Lipid Regulation in Type Two Diabetes Patients |
作者: | Li-Yu Chuang 莊立宇 |
指導教授: | 蔡孟勳 |
關鍵字: | 宏基因組,第二型糖尿病,基因組定序,基因組裝,豐度差異分析, Metagenomics,Type 2 diabetes,Whole genome sequencing,De novo assembly,Differential abundance analysis, |
出版年 : | 2019 |
學位: | 碩士 |
摘要: | 第二型糖尿病是一種主要受遺傳和環境因素所影響的複雜疾病,許多因素包括年齡生活方式和飲食習慣都會影響糖尿病的形成,現今已經成為全世界主要的公眾議題。根據世衛組織的報告,2014年全世界估計有4.22億成年人患有糖尿病,人數是三十多年前的四倍。最近的研究顯示腸道微生物群對於宿主健康的重要性,許多疾病可能有微生物組成失調的情況,包括第二型糖尿病在內的代謝疾病。然而,先前糖尿病相關的研究僅探討正常人和糖尿病患者之間腸道細菌組成的差異,但是細菌對糖尿病病情嚴重程度的影響則尚未研究。微生物早期研究的策略是將單一細菌進行純化和培養,但在人體中存在大量不能被純化培養的微生物。隨著次世代定序的發展,我們可以使用宏基因組方法來分析特定環境中的微生物群組成。因此在本研究中,我們使用344個漢人糞便樣本全基因組定序的公開數據,來研究腸道微生物群豐度變化與糖尿病嚴重程度之間的關聯性。首先,我們建立了一個全基因組定序數據研究的流程來分析腸道微生物,我們從原始定序片段中進行物種分類並且透過統計分析找到一些跟糖尿病嚴重程度有關的細菌特徵,經過篩選過後我們找到兩株可能為潛在生物特徵的菌種.隨後我們構建共同豐度網絡來觀察細菌之間的交互作用以及物種失調的現象是否存在於我們的研究樣本中。為了得到功能分析所需要的組裝序列,我們還進行宏基因組的組裝並且進行評估。最後我們完成對於每個組別之中的基因預測,並且發現在糖尿病嚴重程度不同的病人中存在著某些功能差異。本研究不僅為宏基因組學分析提供了新的分析流程,並且發掘腸道微生物的組成與糖尿病嚴重程度之間關聯性的更多細節。 Type 2 diabetes (T2D) is a complex disorder mainly influenced by both genetic and environmental components, including age, lifestyle and diet, has become a major public issue worldwide. According to the WHO report, there were around 422 million adults worldwide suffering from diabetes in 2014, fourth times more than three decades ago. Recent studies suggested that gut microbiota, which may link to metabolic diseases including T2D has become more important. However, these previous studies mainly focus on bacteria composition differences between normal subjects and diabetic patients, but the effects of bacteria on severity of T2D were still unclear. With the power of next-generation sequencing technology, we can use metagenomic approach to analyze microbiota composition in certain environments. Here, we used a public dataset whichh as fecal shotgun sequencing data from 344 Chinese individuals to characterize the association of gut microbiota abundance with severity of diabetes. We constructed a pipeline for a metagenomic association study. First, we applied taxonomic species-level analysis from raw reads and used statistical method to find several differential markers in different severity of T2D. After filtered and evaluated our findings, we reported two potential bacteria species in our study. Subsequently, we constructed co-abundance networks to investigate whether dysbiosis phenomenon exist in our sample. Furthermore, we performed de novo assembly and quality evaluation to examine the performance of different assemblers in metagenomics sequencing data. At last, we finished gene prediction and find some functional drift between different status in T2D. This study not only provides a new pipeline in metagenomics analysis but also explore more detail with the association between gut microbial composition and the severity of T2D. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/71480 |
DOI: | 10.6342/NTU201900356 |
全文授權: | 有償授權 |
顯示於系所單位: | 生物科技研究所 |
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