比较基因组学平台的设计与实现

Design and construction of the platform for comparative genomics

目的开发一个基于Web的本地服务器支持的功能全面的基因组比较和可视化平台,以加快对基因组的分析。方法构建以Apache HTTP服务器为平台的WEB服务器,采用Perl语言编程,优选整合了MUMmer、LAGAN、Mauve等多个基因组学研究的软件和算法,针对生物学家不同的应用目的,可直接在网页上提交基因组序列数据和参数选项,经平台处理的结果通过网页以图形化的方式返回用户。结果该平台可以处理多种序列数据输入格式,实现了完整的基因组序列和草图基因组序列比对,近远源物种的双基因组或多基因组比对,基因组间的同线性区域寻找,以及定位大范围的基因组重组(基因插入/缺失、重复、重排和水平转移)和小的核苷酸突变等功能;并将结果以图形化的方式显示。应用本平台,对10种新型甲型流感病毒株作基因组同源性分析,表明PB1基因可能来自于人H3N2,PB2、PA基因可能来自于禽类H3N2,而HA、NS基因可能来自于猪H1N1。在本平台上还对结核分枝杆菌(H37Rv、CDC1551)和牛分支杆菌(AF2122/97)基因组的研究分析,发现插入/缺失和重复序列是导致三个菌株基因组差异的主要来源。结论该平台功能资源整合较全面,应用界面友好,结果显示直观,故可作为比较基因组学常规研究的有效平台。

Objective To design a versatile genome comparison and visualization platform based on browser/server mode supported by a local server.Methods The server of the platform was Apache HTTP server.Perl was used to integrate such genome alignment package and algorithms as MUMmer,LAGAN,and Mauve for different comparison purposes,and the users could submit data and parameters to the platform via the web page.The results of analysis were also returned via the web page.Results The platform could handle multiple data input formats,compare complete and draft genome sequence,alignment pair-wise or multi genome of more divergent species,identify regions of high similarity,locate local nucleotide mutations and large-scale recombination,and display the results by visualization interface.Analysis of the homology of 10 new strains of influenza A virus indicated that PB1 gene might evolve from human H3N2 viruses,PB2 and PA genes from avian H3N2 viruses,and HA and NS genes from swine H1N1 viruses.Alignment of Mycobacterium tuberculosis（H37Rv,CDC1551） and Mycobacterium bovis（AF2122/97） genomes revealed that sequence insertion/deletion and duplication were the major source of genomic differences.Conclusion The platform integrate comprehensive resources with a user-friendly interface and intuitive result visualization to facilitate conventional study of comparative genomics.