Using FlyBase to Find Functionally Related Drosophila Genes

Abstract

For more than 25 years, FlyBase ( flybase.org ) has served as an online database of biological information on the genus Drosophila, concentrating on the model organism D. melanogaster. Traditionally, FlyBase data have been organized and presented at a gene-by-gene level, which remains a useful perspective when the object of interest is a specific gene or gene product. However, in the modern era of a fully sequenced genome and an increasingly characterized proteome, it is often desirable to compile and analyze lists of genes related by a common function. This may be achieved in FlyBase by searching for genes annotated with relevant Gene Ontology (GO) terms and/or protein domain data. In addition, FlyBase provides preassembled lists of functionally related D. melanogaster genes within "Gene Group" reports. These are compiled manually from the published literature or expert databases and greatly facilitate access to, and analysis of, established gene sets. This chapter describes protocols to produce lists of functionally related genes in FlyBase using GO annotations, protein domain data and the Gene Groups resource, and provides guidance and advice for their further analysis and processing.

Keywords: D. melanogaster; Database; Drosophila; FlyBase; Functionally related genes; Gene Ontology; Gene group; Protein domain.

Fig. 1

(a) The Gene Ontology (GO) tab of the QuickSearch tool. (b) The Vocabularies tool page, which offers two search options: a search term box (top) and a browsing window to select top-level GO terms (bottom).

Fig. 2

(a) A GO Term report, using the term “smoothened signaling pathway” as an example. (b) The GO section of a Gene report. The gene Ubr3 is shown here as an example.

Fig. 3

(a) The Protein Domains tab of the QuickSearch tool. (b) The “Families and Domains and Molecular Function” section of a Gene report, which includes information on protein domains and Gene Group membership. The gene CASK is shown as an example.

Fig. 4

(a) The Gene Groups tab of the QuickSearch tool. (b) Gene Groups are available as a browsable list. Groups are displayed as a nested hierarchy, with the top-level groups arranged in alphabetical order. The top section of the list is shown from ACETYLCHOLINE RECEPTORS to AUTOPHAGY-RELATED GENES. (c) A Gene Group report, using the ACTINS Gene Group as an example.

Fig. 5

(a) A hit-list of genes. In this example, the hit-list is populated with genes exported from the ION CHANNELS Gene Group. The “Analyze” drop-down menu is shown. (b) A results analysis of individual Biological Process GO terms associated with genes from the ION CHANNELS Gene Group. (Only the top 15 most frequently associated GO terms are shown). (c) A QueryBuilder results page, showing a 2-leg query (top). First query: IDs imported from the ION CHANNELS Gene Group; second query: GO term search for “sensory perception.” A results button, with the number of genes returned from the query, is displayed at the bottom—clicking this generates a new gene hit-list.

Fig. 6

(a) The FlyBase Batch Download interface, using the FlyBase Gene IDs (FBgns) exported from the ACTINS Gene Group as an example. (b) The Batch Download interface for selecting data fields for download (only the top section is shown).

Fig. 7

A Venn diagram showing the overlap between genes annotated with the GO term ‘protein kinase activity’ (GO:0004672) or its child terms, the InterPro term ‘Protein kinase domain’ (IPR000719) and the ‘PROTEIN KINASE’ Gene Group. The diagram was generated using Venny 2.1.