建構健康族群與人類癌症拷貝數變異之整合型資料庫

A Comprehensive Database Integrating Copy Number Variation Profile in Healthy Individuals and Human Cancer

張子涵(Zi-Han Teoh)

指導教授 ： 莊曜宇

共同指導教授 ： 盧子彬

國立臺灣大學/電機資訊學院/生醫電子與資訊學研究所/碩士(2019年)

https://doi.org/10.6342/NTU201901550

摘要

拷貝數變異（copy number variation, CNV）是一種基因變異，係指因DNA序列上存有大於1000個鹼基對的序列改變，所導致位於此序列改變區段之基因在拷貝數上偏離正常參考標準的情形。目前已有許多研究證實CNV可透過劑量效應（dosage effect）調節基因的表現，進而導致基因調節機制的失衡，並且影響包括癌症在內多種疾病的表現和進程。許多致力於探討癌症與CNV之間關聯的研究也提出了CNV在癌症的診斷與治療上作為生物標定物（biomarker）的關鍵作用。為了探討CNV在癌症中所扮演的角色，CNV相關的生物實驗數量在近年來有大幅增加的趨勢。儘管如此，截至目前仍沒有一個以CNV為導向的線上資源可以讓研究人員以系統化的方式獲取CNV相關資料並做出分析比較，進而耗費了過多的時間和精力。

因此在這項研究中，我們整合了來自健康族群，癌症病患和癌症細胞株的CNV概況，並建置了一個完善且對使用者友善的線上資料庫，以改善CNV數據探勘、檢索和分析的相關流程。我們除了收錄了22155個基因在健康人當中的CNV頻率以作為基準參考標準，也同時構建了70種人類癌症的CNV情形。最後亦透過這個資料庫的分析功能，比較542名肺腺癌患者和健康個體的CNV數據來進一步證實這個系統的潛在應用。我們希望透過網站上所提供的簡易查詢系統和在線分析模式來去除技術上的隔閡，並提供研究者高效且易於操作的分析平台。我們相信這個資料庫可作為CNV研究中一個重要的工具，幫助研究人員統一處理、比較和檢索CNV數據。除了協助探討CNV在疾病中扮演的角色以外，也可篩選出有潛力成為癌症標定物之基因。

關鍵字

拷貝數變異 ； 健康臺灣族群 ； 癌症CNV ； 資料庫 ； 線上系統 ； 使用者友善 ； 肺腺癌

並列摘要

Copy number variation (CNV) is a region with structural variation in which the genomic copy numbers (CN) differs when compared to the reference genome. It is classically defined as a genomic segment that consists of at least 1000 base pairs of sequence alterations. In human genome, CNV may cause genomic imbalance by regulating gene expression levels through dosage effect and has been associated with multiple disease, including cancer. Thus far, many researchers have studied the relationship between cancer and CNV, providing intriguing insights into CNV roles as cancer biomarker. Despite an intensive increase in the amount of related biological validation experiments, the distinct lack of an integrated resource that supports highly-efficient CNV research has drive our study to construct a comprehensive online database to simplify the data mining, retrieval, and analysis processes of CNV investigations. In this study, we integrate the CNV profiles of healthy populations, cancer patients, and cancer cell lines from various sources. The baseline CNV frequency of 22155 genes serving as comparisons benchmark were established, and we constructed the CNV profile of 70 types of human cancer. We further demonstrate the potential application of this system by analyzing CNV data from 542 lung adenocarcinoma patients. With the provision of an easy query and online submission analysis schema, we expect that this database would serve as an important tool to assist researchers in uniformly processing, comparing and retrieving CNV data, as well as in facilitating the clinical interpretation and discoveries of significant CNVs.

並列關鍵字

copy number variation ； healthy Taiwanese populations ； cancer CNV ； database ； online system ； user-friendly ； lung adenocarcinoma

參考文獻

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