Computatonal Analysis of Gene Expression Pattern Images

描述（由申请人提供）： 后生动物是最复杂的生命形式，其中体型的复杂性是通过发育胚胎中基因表达的时空模式及其调控来实现的。果蝇一直是研究这种复杂性如何产生的模型系统，通过检查描述发育胚胎中关键基因的mRNA或蛋白质定位的基因表达模式。探索特定基因或基因家族的研究人员通常有兴趣寻找具有重叠基因表达模式的其他基因，以阐明发育途径。然而，既不存在这些基因表达模式图像的生物数据库，也不存在用于（1）发现相似基因表达模式和（2）访问与已知遗传相互作用相关的知识的计算框架。因此，我们建议建立一个果蝇基因表达系统（FlyExpress）的检索和可视化的基因表达的空间和时间模式在果蝇胚胎和成虫盘。建议的生物信息学框架将有助于查询具有相似的表达模式的基因在时间，空间和器官的具体情况。除了基于生物属性的文本搜索外，我们还将开发一个基本表达搜索工具视觉内容查询系统，以帮助发现重叠的基因表达模式（Fx-BEST）。Fx-BEST功能将类似于分子序列分析中的BLAST搜索功能。 我们还计划开发计算工具来生成器官和位置特异性基因表达模式类（Fx分类），其中显示显著重叠的表达模式将被分组在同一类中。 由此产生的分类将允许专家研究人员使用这些表达模式的生物学，发育和遗传属性来预测基因或发育途径成员之间潜在的新相互作用。此外，我们计划设计计算方法来比较（以类似于发育生物学家所做的方式）野生型和突变背景中给定基因的表达模式，以推断潜在的遗传相互作用（Fx相互作用）。该技术将用于自动生成使用Fx数据库中的数据构建的所有基因相互作用。这些相互作用可以用来建立进一步的假设，在研究实验室进行测试。FlyExpress将在网站上免费提供（www.flyexpress.net）。它不仅将满足研究人员的日常需求，还将为利用现有知识（约50，000张图像及其属性）进行进一步发现提供框架。此外，计算算法，统计方法和生物信息学技术在这个项目中开发的将是有用的，并提供动力，为组织基因表达模式数据从其他模式和非模式生物构建类似的框架。拟议中的FlyExpress信息系统将直接促进对人类健康研究至关重要的分子生物学许多领域的基础和应用研究，包括计算基因组学，分子遗传学，发育生物学，遗传学和进化。它也有可能成为世界各地大学本科生和研究生的宝贵教学资源

DESCRIPTION (provided by applicant): Metazoans are the most complex life forms in which the complexity of body form is achieved by spatial and temporal patterns of gene expression and its regulation in the developing embryo. The Drosophila melanogaster has been a model system to study how this complexity arises by examining the gene expression patterns depicting the mRNA or protein localization of key genes in the developing embryo. Investigators exploring a specific set of genes or gene families are often interested in finding other genes with overlapping patterns of gene expression in order to elucidate developmental pathways. However, neither a biological database of these gene expression pattern images nor a computational framework exists (1) to find similar gene expression patterns, and (2) to access knowledge related to the known genetic interactions. Therefore, we propose to build a fruit-fly gene expression system (FlyExpress) for retrieval and visualization of spatial and temporal patterns of gene expression in Drosophila embryos and imaginal disks. The proposed bioinformatics framework will facilitate query for genes with similar expression patterns in the temporal, spatial, and organ specific contexts. In addition to text search based on biological attributes, we will develop a Basic Expression Search Tool visual-content query system to assist in the discovery of overlapping gene expression patterns (Fx-BEST). The Fx-BEST functionality will be analogous to that of BLAST search in molecular sequence analysis. We also plan to develop computational tools to generate organ and position specific gene expression pattern classes (Fx-Classify), where expression patterns showing significant overlap will be grouped in the same class. The resulting classification will allow expert investigators to use biological, developmental, and genetic attributes of these expression patterns to predict potentially new interactions among genes or members of developmental pathways. In addition, we plan to devise computational approaches to compare (in a manner similar to that done by developmental biologists) the expression pattern of a given gene in wild type and mutation backgrounds in order to infer the underlying genetic interactions (Fx-Interaction). This technique will be used to automatically generate all gene interactions constructed using the data curated in the Fx- Database. These interactions can be used to establish further hypotheses for testing in research laboratories. FlyExpress will be made freely accessible on the web (www.flyexpress.net). It will not only address the day-to-day needs of researchers, but will also provide a framework for further discovery using the existing knowledge (approximately 50,000 images and their attributes). Furthermore, the computational algorithms, statistical methods, and the bioinformatics technologies developed in this project will be useful and provide impetus for constructing similar frameworks for organizing gene expression pattern data from other model and non-model organisms. The proposed FlyExpress informatics system will directly facilitate basic and applied research in many areas of molecular biology crucial in human health research, including computational genomics, molecular genetics, developmental biology, genetics, and evolution. It is also likely to become a valuable teaching resource for undergraduate and graduate students at universities worldwide