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標題: | VariED: 基於心臟疾病的變異與基因表達的整合型資料庫 VariED: an integrated database of variants and gene expression profiles for heart diseases |
作者: | Li-Mei Chiang 姜莉玫 |
指導教授: | 莊曜宇(Eric Y. Chuang) |
共同指導教授: | 盧子彬 |
關鍵字: | 心臟疾病,基因變體,人群等位基因頻率,基因表現圖譜,資料庫,線上系統, heart disease,genetic variant,population allele frequency,gene expression profiles,database,web-based system, |
出版年 : | 2018 |
學位: | 碩士 |
摘要: | 心臟疾病近幾年來皆為世界十大死因前幾名,且花費也有逐年增高的趨勢,為了找到解決的辦法,越來越多研究者參與心臟疾病的研究,然而從活體取得心臟組織不容易,其他組織部位與心臟的基因表現圖譜可能不一致,因而造成找到可能會發生致病變體,但變體所在的基因卻不會在心臟表現的情形。為了解決基因表現圖譜在不同組織之間表達不同的問題,並且幫助研究者分析變體跟族群與疾病之間的關係,本研究的目的是建立一個心臟全面性的資料庫,因應前面提到的需求,提供兩種服務,Expression profiles和Variants Search,前者用於查詢基因相關訊息,並且用於確認目標基因是否會在心臟組織表現;而後者用於獲取變體多方面訊息。
在這項研究中,我們提出一個網頁式介面操作的變體和心臟組織基因表現圖譜的資料庫,統整了人類、老鼠、斑馬魚的心臟基因表現圖譜資料,以及1000 Genomes Project、National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP) 、Integrative Japanese Genome Variation Database (IJGVD)和臺灣人體生物資料庫等發表的各大族群遺傳變體的參考資料,此外我們也收集了REVEL、GERP++、CADD等分數,用來預測可能引起疾病的變體,並且建立Index 系統,有別於以往變體分析工具,index系統加入了組織基因表現要素。此外,為了幫助研究者將變體做臨床上的連結,ClinVar發表的變體表型等資訊也整合進VariED。在結果上,我們運用幾個例子展現了VariED的應用,我們成功從多個基因中找到不會在心臟表現的基因,也以三個布魯格達氏症候群相關變體,展現VariED找到致病的變體的能力;index 系統提供的數值也能用來成功找到致病的變體,並且與CADD分數有中度相關。總言之,VariED藉由整合各大資料庫與工具的數據來提供全面性的服務,幫助研究人員減少搜索資料的時間成本,並促進心臟疾病的研究。 Heart disease is the top ten causes of death in the world and the cost of heart disease is also increasing year by year. In order to improve the understanding of heart diseases, more and more research efforts have been devoted to the heart disease researches. However, it is difficult to gather heart tissue directly from human patients, and the gene expression profiles obtained from other tissues may be different from that of the heart. Thus, it is possible to obtain a pathogenic variant which is in a gene but does not express in the heart tissue. To overcome this problem and support researchers to analyze the relationship among variants, populations, and heart diseases, we developed a comprehensive database for heart diseases. As mention above, VariED provides two major functions, Expression Profiles and Variants Search. The former is used to query gene information and confirm whether the target gene expresses in heart tissue; the latter is used to obtain more detailed information of the interested variants. In this study, we developed a web-based database integrating variants and tissue-based expression profiles in heart from three species, including human, mouse and zebrafish. In addition, the population allele frequency from the 1000 Genomes Project, National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP), Integrative Japanese Genome Variation Database (IJGVD), and Taiwan Biobank were included. We also collected REVEL, GERP++, and CADD scores that can help to elucidate the functional roles of interested variants for diseases. Subsequently, an index scoring system was implemented in VariED. The uniqueness for the scoring system is that we consider tissue-based gene expression level as an important factor in the prediction. Lastly, to help researchers identify causative variants in diseases, a public database named as ClinVar which collected the associations between DNA variants and diseases was integrated. In this thesis, we used several examples to show the potential applications of VariED. For examples, we successfully identified a gene which does not express in heart tissue. Three Brugada syndrome-related variants were analyzed to demonstrate the usage of VariED to find pathogenic variants. We believe VariED not only assists researchers to save time for querying data, but also helps users to identify important DNA variants related to diseases. |
URI: | http://tdr.lib.ntu.edu.tw/handle/123456789/1226 |
DOI: | 10.6342/NTU201804200 |
全文授權: | 同意授權(全球公開) |
顯示於系所單位: | 生醫電子與資訊學研究所 |
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