PDF(Pubmed)
Abstract：
Systematic functional profiling of the gene set that directs embryonic development is an important challenge. To tackle this challenge, we used 4D imaging of C. elegans embryogenesis to capture the effects of 500 gene knockdowns and developed an automated approach to compare developmental phenotypes. The automated approach quantifies features-including germ layer cell numbers, tissue position, and tissue shape-to generate temporal curves whose parameterization yields numerical phenotypic signatures. In conjunction with a new similarity metric that operates across phenotypic space, these signatures enabled the generation of ranked lists of genes predicted to have similar functions, accessible in the PhenoBank web portal, for ∼25% of essential development genes. The approach identified new gene and pathway relationships in cell fate specification and morphogenesis and highlighted the utilization of specialized energy generation pathways during embryogenesis. Collectively, the effort establishes the foundation for comprehensive analysis of the gene set that builds a multicellular organism.
摘要：
指导胚胎发育的基因组的系统功能分析是一个重要的挑战。为了应对这一挑战，我们使用C.elegans胚胎发生的4D成像来捕获500个基因敲除的影响，并开发了一种自动化方法来比较发育表型。自动化方法量化特征-包括胚层细胞数，组织位置,和组织形状-生成其参数化产生数值表型特征的时间曲线。结合跨表型空间运行的新相似性度量，这些特征使得能够生成预测具有相似功能的基因的排名列表，在PhenoBank门户网站中访问，25%的必需发育基因。该方法确定了细胞命运规范和形态发生中的新基因和途径关系，并强调了胚胎发生过程中专门能量产生途径的利用。总的来说，这项工作为全面分析构建多细胞生物的基因集奠定了基础。
