電腦化預測宿主微小核醣核酸在病毒基因組的靶位點以及預測病毒微小核醣核酸

Abstract

近年來發現微小核醣核酸(microRNA)於哺乳動物、植物與昆蟲中，藉由調控後轉錄作用產物，在發育、致癌及細胞凋亡上扮演重要的角色。值得注意的是，微小核醣核酸不僅在真核生物中存在，病毒亦能產生微小核醣核酸，且病毒感染宿主後，宿主細胞中的微小核醣核酸也具有調控病毒的功能。因此，我們建置ViTa和 VirMiR兩個資料庫來收集病毒產生的微小核醣核酸，及探討病毒與宿主微小核醣核酸間的關係。資料的收集上，來自病毒和四各物種中，已知的微小核醣核酸分別從miRBase和miRNAMap得來。病毒的資訊則收集自四各資料庫：NCBI、ICTVdB、VBRC和VirGen。已知的宿主微小核醣核酸靶位點，則藉由瀏覽論文而得。另外，病毒上微小核醣核酸的預測主要專注於染色體上的保存區段。預測宿主小核醣核酸在病毒上的靶位點，則利用兩個軟體：miRanda和TargetScan來提升預測準確度。另外也提供相關的註解、被病毒感染的組織以及微小核醣核酸的組織專一性等。最後，所有的資訊均整合以研究微小核醣核酸與病毒間的相關性。 我們亦為使用者提供某些病毒間亞種的比較，像是流感病毒與肝癌病毒，及同一種類中不同病毒株間的保存區段。為便利資料的取得及協助研究，網站同時提供文字與圖形介面。目前這兩個資料庫ViTa和VirMiR已分別建置在http://vita.mbc.nctu.edu.tw/ 和http://virmir.mbc.nctu.edu.tw/。

Recent work has indicated that microRNAs (miRNAs) play important roles on development, oncogenesis and apoptosis by binding to mRNAs to regulate the post-transcriptional level of gene expression in mammals, plants and insects. Notably, miRNAs also can be produced from virus, and the expression of virus genes are potentially regulated by host miRNAs after infecting host. In this thesis, two databases, VirMiR and ViTa, are developed to compile the virus miRNAs and the regulatory relationships between host miRNAs and virus genes, respectively. Known virus microRNAs in four species, such as humans, mouse, rat and chicken, were obtained from miRBase and miRNAMap. Virus information was collected from NCBI, ICTVdB, VBRC and VirGen. Experimentally validated host miRNA targets on viruses are identified via a literature survey. Then, miRanda and TargetScan are applied to identify the miRNA targets within virus genomes. The virus miRNAs were detected based on comparative sequence analysis. Finally, virus annotations, virus infected tissues from literatures and tissue-specificity of miRNAs from MIT are integrated, and the possible relationship between miRNAs and viruses are identified. This work also provides comparisons between subtypes in some common viruses, such as influenza viruses, liver viruses, and conserved regions between different strains of the same virus species for users. Both textual and graphical web interfaces are provided to facilitate data retrieval from the two databases. The two databases can be available on the Internet at http://vita.mbc.nctu.edu.tw/ and http://virmir.mbc.nctu.edu.tw/.