Max-Planck Institute for Molecular Genetics, Berlin, Germany .
Zebrafish. 2013 Sep;10(3):303-15. doi: 10.1089/zeb.2012.0865. Epub 2013 May 8.
The zebrafish (Danio rerio) is an established model organism for developmental and biomedical research. It is frequently used for high-throughput functional genomics experiments, such as genome-wide gene expression measurements, to systematically analyze molecular mechanisms. However, the use of whole embryos or larvae in such experiments leads to a loss of the spatial information. To address this problem, we have developed a tool called Zebrafish Expression Ontology of Gene Sets (ZEOGS) to assess the enrichment of anatomical terms in large gene sets. ZEOGS uses gene expression pattern data from several sources: first, in situ hybridization experiments from the Zebrafish Model Organism Database (ZFIN); second, it uses the Zebrafish Anatomical Ontology, a controlled vocabulary that describes connected anatomical structures; and third, the available connections between expression patterns and anatomical terms contained in ZFIN. Upon input of a gene set, ZEOGS determines which anatomical structures are overrepresented in the input gene set. ZEOGS allows one for the first time to look at groups of genes and to describe them in terms of shared anatomical structures. To establish ZEOGS, we first tested it on random gene selections and on two public microarray datasets with known tissue-specific gene expression changes. These tests showed that ZEOGS could reliably identify the tissues affected, whereas only very few enriched terms to none were found in the random gene sets. Next we applied ZEOGS to microarray datasets of 24 and 72 h postfertilization zebrafish embryos treated with beclomethasone, a potent glucocorticoid. This analysis resulted in the identification of several anatomical terms related to glucocorticoid-responsive tissues, some of which were stage-specific. Our studies highlight the ability of ZEOGS to extract spatial information from datasets derived from whole embryos, indicating that ZEOGS could be a useful tool to automatically analyze gene expression pattern features of any large zebrafish gene set.
斑马鱼（Danio rerio）是发育和生物医学研究的成熟模式生物。它常用于高通量功能基因组学实验，如全基因组基因表达测量，以系统地分析分子机制。然而，在这些实验中使用整个胚胎或幼虫会导致空间信息的丢失。为了解决这个问题，我们开发了一种名为 Zebrafish Expression Ontology of Gene Sets（ZEOGS）的工具，用于评估大基因集中解剖学术语的富集情况。ZEOGS 使用来自多个来源的基因表达模式数据：首先，来自 Zebrafish Model Organism Database（ZFIN）的原位杂交实验；其次，它使用描述连接解剖结构的受控词汇 Zebrafish Anatomical Ontology；第三，ZFIN 中包含的表达模式和解剖术语之间的可用连接。输入基因集后，ZEOGS 确定输入基因集中哪些解剖结构过表达。ZEOGS 允许人们首次观察基因群，并根据共享的解剖结构对其进行描述。为了建立 ZEOGS，我们首先在随机基因选择和两个具有已知组织特异性基因表达变化的公共微阵列数据集上对其进行了测试。这些测试表明，ZEOGS 能够可靠地识别受影响的组织，而在随机基因集中仅发现了极少数富集术语甚至没有。接下来，我们将 ZEOGS 应用于 24 小时和 72 小时后受精斑马鱼胚胎用倍氯米松处理的微阵列数据集，倍氯米松是一种有效的糖皮质激素。该分析确定了几个与糖皮质激素反应组织相关的解剖学术语，其中一些具有特定的阶段特异性。我们的研究强调了 ZEOGS 从整个胚胎衍生的数据集提取空间信息的能力，表明 ZEOGS 可能是一种有用的工具，可以自动分析任何大型斑马鱼基因集的基因表达模式特征。
