建置新一代高通量定序分析平台---從定序、功能、到系統生物網路---利用次世代定序資料進行基因體重組的研究與結構變異的偵測

Abstract

次世代定序(NGS)技術使得基因體的定序愈來愈快也愈來愈便宜，可以預期不久的將來會有許多物種的 基因體被NGS 技術給定序出來。然而目前NGS 技術所定序出來的基因體大都只是由一些前後次序未知 的contigs/scaffolds 所組成的草圖。雖然這些基因體草體可能就已足夠讓科學家進行許多比較基因體的分 析，但卻不能直接被拿來進行基因體重組的研究，因為目前被設計出來的基因體重組演算法需要完整的 基因體資料，基因體裡的每一個染色體皆用基因或標記的次序來表示，才能夠去計算出二個基因體之間 的重組距離。因此如何設計出有效率的基因體重組演算法把前後次序未知的contigs/scaffolds 給組合起來 並正確地計算出組合基因體之間的重組距離，以及如何利用這些重組距離去建構出不同物種之間的演化 關係將是本子計劃的主要研究課題之一。除此之外，本子計劃也將進一步去研究如何偵測出發生在這些 組合基因體上大規模的結構變異，這些結構變異(包含DNA 片斷的插入、刪除、翻轉、移位、區段互 換、易位、融合、分裂等)常與癌症的發生息息相關，因此找出癌症基因體上的結構變異將有助於人類癌 症與其它疾病的診斷與治療，同時也可幫助我們了解基因體在生命演化的過程中是如何成形的。

Due to the high speed and low cost of next generation sequencing (NGS) technologies, it can be expected that more and more species genomes will be sequenced by NGS in near future. However, many genomes sequenced by current NGS technologies are in unfinished form and therefore they are just draft genomes that consist of unordered contigs and/or scaffolds. Although these draft genomes may be sufficient for scientists to perform some comparative genomic analyses, they cannot directly be used in genome rearrangement studies because currently available algorithms for studying genome rearrangements require whole genome data, in which each chromosome is represented in terms of gene (or marker) order, to calculate the rearrangement distance between two genomes. Therefore, it is one of our major researches in this component project to study how to design efficient genome rearrangement algorithms to assemble the unordered contigs and/or scaffolds in draft genomes and accurately calculate the rearrangement distance between the assembled genomes, and also study how to further use the calculated rearrangement distances to construct the evolutionary relationships among different species. In this component project, we are also going to study how to detect the large-scale structural variation in the assembled genomes. These structural variants (including insertion, deletion, inversion/reversal, transposition, block-interchange, translocation, fusion, fission and son on) frequently associate with cancers in the human genome. Therefore, the detection of the structural variations in the tumor genomes is helpful for the diagnosis and treatment of human cancers and other diseases. Moreover, it is helpful for us to understand how the current species genomes are shaped during the evolutionary history of life.