Database Commons

a catalog of worldwide biological databases

FlyAtlas 2 (www.flyatlas2.org) is part successor, part complement to the FlyAtlas database and web application for studying the expression of the genes of Drosophila melanogaster in different tissues of adults and larvae. Although generated in the same lab with the same fly line raised on the same diet as FlyAtlas, the FlyAtlas2 resource employs a completely new set of expression data based on RNA-Seq, rather than microarray analysis, and so it allows the user to obtain information for the expression of different transcripts of a gene. Furthermore, the data for somatic tissues are now available for both male and female adult flies, allowing studies of sexual dimorphism. Gene coverage has been extended by the inclusion of microRNAs and many of the RNA genes included in Release 6 of the Drosophila reference genome. The web interface has been modified to accommodate the extra data, but at the same time has been adapted for viewing on small mobile devices. Users also have access to the RNA-Seq reads displayed alongside the annotated Drosophila genome in the (external) UCSC browser, and are able to link out to the previous FlyAtlas resource to compare the data obtained by RNA-Seq with that obtained using microarrays.

The FlyAtlas resource contains data on the expression of the genes of Drosophila melanogaster in different tissues (currently 25-17 adult and 8 larval) obtained by hybridization of messenger RNA to Affymetrix Drosophila Genome 2 microarrays. The microarray probe sets cover 13,250 Drosophila genes, detecting 12,533 in an unambiguous manner. The data underlying the original web application (http://flyatlas.org) have been restructured into a relational database and a Java servlet written to provide a new web interface, FlyAtlas 2 (http://flyatlas.gla.ac.uk/), which allows several additional queries. Users can retrieve data for individual genes or for groups of genes belonging to the same or related ontological categories. Assistance in selecting valid search terms is provided by an Ajax 'autosuggest' facility that polls the database as the user types. Searches can also focus on particular tissues, and data can be retrieved for the most highly expressed genes, for genes of a particular category with above-average expression or for genes with the greatest difference in expression between the larval and adult stages. A novel facility allows the database to be queried with a specific gene to find other genes with a similar pattern of expression across the different tissues.

Comparative analysis of tissue-specific transcriptomes is a powerful technique to uncover tissue functions. Our FlyAtlas.org provides authoritative gene expression levels for multiple tissues of Drosophila melanogaster (1). Although the main use of such resources is single gene lookup, there is the potential for powerful meta-analysis to address questions that could not easily be framed otherwise. Here, we illustrate the power of data-mining of FlyAtlas data by comparing epithelial transcriptomes to identify a core set of highly-expressed genes, across the four major epithelial tissues (salivary glands, Malpighian tubules, midgut and hindgut) of both adults and larvae. Parallel hypothesis-led and hypothesis-free approaches were adopted to identify core genes that underpin insect epithelial function. In the former, gene lists were created from transport processes identified in the literature, and their expression profiles mapped from the flyatlas.org online dataset. In the latter, gene enrichment lists were prepared for each epithelium, and genes (both transport related and unrelated) consistently enriched in transporting epithelia identified. A key set of transport genes, comprising V-ATPases, cation exchangers, aquaporins, potassium and chloride channels, and carbonic anhydrase, was found to be highly enriched across the epithelial tissues, compared with the whole fly. Additionally, a further set of genes that had not been predicted to have epithelial roles, were co-expressed with the core transporters, extending our view of what makes a transporting epithelium work. Further insights were obtained by studying the genes uniquely overexpressed in each epithelium; for example, the salivary gland expresses lipases, the midgut organic solute transporters, the tubules specialize for purine metabolism and the hindgut overexpresses still unknown genes. Taken together, these data provide a unique insight into epithelial function in this key model insect, and a framework for comparison with other species. They also provide a methodology for function-led datamining of FlyAtlas.org and other multi-tissue expression datasets.

FlyAtlas, a new online resource, provides the most comprehensive view yet of expression in multiple tissues of Drosophila melanogaster. Meta-analysis of the data shows that a significant fraction of the genome is expressed with great tissue specificity in the adult, demonstrating the need for the functional genomic community to embrace a wide range of functional phenotypes. Well-known developmental genes are often reused in surprising tissues in the adult, suggesting new functions. The homologs of many human genetic disease loci show selective expression in the Drosophila tissues analogous to the affected human tissues, providing a useful filter for potential candidate genes. Additionally, the contributions of each tissue to the whole-fly array signal can be calculated, demonstrating the limitations of whole-organism approaches to functional genomics and allowing modeling of a simple tissue fractionation procedure that should improve detection of weak or tissue-specific signals.