Evolutionary functional genomics: a bioinformatics approach

最近的生物技术进步导致了三个主要的细胞成分：基因组，转录组和蛋白质组越来越准确的表征。基因组学、转录组学和蛋白质组学数据的快速积累需要先进的生物信息学工具来将令人困惑的分子数据量转化为有组织的知识和细胞组分之间相互作用的数学建模。我们实验室的软件包已被广泛用于分子生物遗传学，将进化历史追溯到远古时代，并用于DNA微阵列数据分析，从而越来越准确地表征活细胞如何工作（或它们如何在癌症中失败）。我们的研究模拟生物和进化过程，增强了对三个基本和基本生物过程的理解，即，基因组复制，转录和翻译，在所有生物体中共享。在我们实验室进行的比较基因组分析揭示了突变和选择之间的相互作用模式，在各种各样的生物体中形成了这三个过程。拟议的项目将导致（1）更好地了解人类胃病原体幽门螺杆菌通过基因组适应在酸性环境中的分子适应，（2）改进分析转录组数据的方法，以监测脊椎动物中的基因表达如何对环境化学品和药品作出反应，（3）逆转录病毒关闭宿主翻译机制但维持自身蛋白质翻译的秘密，（4）更好的系统发育方法，以跟踪基因和基因组的进化，并确定物种形成和基因复制事件的日期，以及（5）广泛使用的软件包，有助于将不断增加的分子信息量自动转换为有组织的知识。特别是，它将使加拿大学生成为生物信息学研究的领导者，这些研究深深植根于对突变和选择不断塑造的动态细胞过程的基本理解。

Recent biotechnological advances have resulted in an increasingly accurate characterization of the three major cellular components: genome, transcriptome and proteome. The rapid accumulation of genomic, transcriptomic and proteomic data demand advanced bioinformatic tools to convert the bewildering amount of molecular data into organized knowledge and mathematical modeling of interactions among the cellular components. Software packages from our laboratory have been widely used in molecular phylogenetics that traces the evolutionary history back into time immemorial, and in DNA microarray data analysis that leads to increasingly accurate characterization of how living cells work (or how they fail to work as in cancer). Our research modeling biological and evolutionary processes has enhanced the understanding of the three essential and fundamental biological processes, i.e., genome replication, transcription and translation, shared among all living entities. Comparative genomic analysis carried out in our lab has revealed the pattern of interplay between mutation and selection in shaping the three processes across a wide variety of organisms. The proposed project will lead to (1) better understanding of the molecular adaptation of the human gastric pathogen, Helicobacter pylori, in acidic environment through genomic adaptation, (2) improved methods for analyzing transcriptomic data that monitor how gene expression in vertebrates will respond to environmental chemicals and pharmaceutical products, (3) the secret of retroviruses in shutting down their host translation mechanism yet maintaining the translation of their own proteins, (4) better phylogenetic methods to follow the evolution of genes and genomes and to date speciation and gene duplication events, and (5) widely used software packages contributing to the automation of converting the ever increasing amount of molecular information to organized knowledge. In particular, it will prepare Canadian students to become leaders in bioinformatics research deeply rooted in a fundamental understanding of dynamic cellular processes constantly shaped by mutation and selection.