FlyNet

remains an important model organism even after a century of research. Numerous biological processes that have been evolutionary conserved across species, such as embryogenesis and canonical cell signaling pathways, have been genetically dissected in Drosophila. Approximately half of Drosophila protein sequences have mammalian homologs, and approximately 75% of known human disease genes have Drosophila orthologs. Drosophila therefore is expected to be an effective model for human disease research.

Genetic dissection of the pathways and phenotypes using reverse-genetics approach can be facilitated by systematic gene prioritization. Recently, effectiveness of network-assisted gene prioritization for complex traits has been demonstrated in many organisms. Hence we constructed a fly network prioritization server, FlyNet, which includes a network of 13,119 fly genes (~95% of the coding genes) and 779,484 links. FlyNet has several distinctive features that enable more versatile hypothesis generation for Drosophila-based studes.

• FlyNet can prioritize both genes (gene prioritization) and functional annotations (function prioritization).
• FlyNet can use two complementary network prioritization algorithms, direct neighborhood and network diffusion.
• FlyNet can utilize a spatiotemporal-specific network (STN) as an additional prioritization strategy for traits associated with a specific development stage or tissue.
• FlyNet can prioritize Drosophila genes not only for Drosophila traits (fly prioritizer) but also for human disease (human prioritizer).

• Fly function prioritization option ranks GOBP terms and RNAi phenotypes for a query gene.
• Fly gene prioritization option ranks fly genes from the most closely associated to the guide genes by either direct neighborhood or network diffusion algoritm. Based on ranks of the guide genes, the server measures predictive power of FlyNet by using ROC analysis. It also provides spatiotemporal-specific network analysis for traits associated with specific developmental stage or tissue. This option also provides network visualization and gene set analysis with REVIGO module.
• Human disease gene prioritization option can use both fly genes and human genes as guide genes for network search. Users can use additional option of support genes to further filtration for more confident candidates. Support genes from human genome-wide association studies and de novo mutation screens are currently available in the FlyNet server, and users can submit their own list of support genes.

FlyNet: a versatile network prioritization server for the Drosophila community, Nucleic Acids Research 2015 Jul 1;43(W1):W91-7 (PubMed)

Insuk Lee (insuklee (at) yonsei.ac.kr)

This work was supported by the National Research Foundation of Korea grant (2012M3A9B4028641, 2012M3A9C7050151).