Dataset Information

Zebrafish Expression Ontology of Gene Sets (ZEOGS): a tool to analyze enrichment of zebrafish anatomical terms in large gene sets.

ABSTRACT: 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.

SUBMITTER: Prykhozhij SV

PROVIDER: S-EPMC3760060 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Zebrafish Expression Ontology of Gene Sets (ZEOGS): a tool to analyze enrichment of zebrafish anatomical terms in large gene sets.

Prykhozhij Sergey V SV Marsico Annalisa A Meijsing Sebastiaan H SH

Zebrafish 20130508 3

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 asse ...[more]

PMID: 23656298

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Project description:BACKGROUND: Reliability and Reproducibility of differentially expressed genes (DEGs) are essential for the biological interpretation of microarray data. The microarray quality control (MAQC) project launched by US Food and Drug Administration (FDA) elucidated that the lists of DEGs generated by intra- and inter-platform comparisons can reach a high level of concordance, which mainly depended on the statistical criteria used for ranking and selecting DEGs. Generally, it will produce reproducible lists of DEGs when combining fold change ranking with a non-stringent p-value cutoff. For further interpretation of the gene expression data, statistical methods of gene enrichment analysis provide powerful tools for associating the DEGs with prior biological knowledge, e.g. Gene Ontology (GO) terms and pathways, and are widely used in genome-wide research. Although the DEG lists generated from the same compared conditions proved to be reliable, the reproducible enrichment results are still crucial to the discovery of the underlying molecular mechanism differentiating the two conditions. Therefore, it is important to know whether the enrichment results are still reproducible, when using the lists of DEGs generated by different statistic criteria from inter-laboratory and cross-platform comparisons. In our study, we used the MAQC data sets for systematically accessing the intra- and inter-platform concordance of GO terms enriched by Gene Set Enrichment Analysis (GSEA) and LRpath. RESULTS: In intra-platform comparisons, the overlapped percentage of enriched GO terms was as high as ~80% when the inputted lists of DEGs were generated by fold change ranking and Significance Analysis of Microarrays (SAM), whereas the percentages decreased about 20% when generating the lists of DEGs by using fold change ranking and t-test, or by using SAM and t-test. Similar results were found in inter-platform comparisons. CONCLUSIONS: Our results demonstrated that the lists of DEGs in a high level of concordance can ensure the high concordance of enrichment results. Importantly, based on the lists of DEGs generated by a straightforward method of combining fold change ranking with a non-stringent p-value cutoff, enrichment analysis will produce reproducible enriched GO terms for the biological interpretation.

Dataset Information

Zebrafish Expression Ontology of Gene Sets (ZEOGS): a tool to analyze enrichment of zebrafish anatomical terms in large gene sets.

Publications

Zebrafish Expression Ontology of Gene Sets (ZEOGS): a tool to analyze enrichment of zebrafish anatomical terms in large gene sets.

Similar Datasets

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