RPGeNet is a web application tool created to help users find new potential driver genes of retinitis pigmentosa and help better visualize the complex interaction network of the retina. The interaction database is formed by the merger of self-curated BioGRID, STRING and text-mining (PPaxe) interaction data. The driver genes are retrieved from the RetNet website.
Once the data is gathered, a graph building program is implemented beginning with the construction of the skeleton – a graph made up of all the shortest interactions between the known driver genes of retinital dystrophies. The skeleton graph includes 4,018 genes/nodes and 35,528 interactions/edges. From the skeleton graph (level 0), the program builds higher levels that are an expansion in the network by adding children and parent nodes not already found in the network [see figure above]. Eventually the graph saturates at level 3 and only a few genes that do not connect with the interactions graph, but may interact with themselves or with genes that do not connect with the rest of the graph, are added in as part of the whole graph. The whole graph currently contains a total of 18,542 genes and 1,218,032 interactions.
Researchers interested in finding candidate driver genes of retinal dystrophies would primarily be searching through the skeleton graph.
Here is where you can input one or several genes of interest related or unrelated to Retinitis Pigmentosa (RP) (althought if is not related there is a big change that it won't have interactors, since the network is using RP genes as seeds). If the input are multiple genes, then those genes have to be separated be a comma "," or a blank space " " between them.
The RP network has 4 levels: "Skeleton", Level 1, Level 2, Level 3, and WholeGraph. Each level represents a sub-network of genes and interactions ranging from more related to Retinitis Pigmentosa (Skeleton) to less related (WholeGraph).
Specify the distance from the input genes to retrieve from the Network. By default this is set to 1, that is, RPGeNet will only retrieve parents and childs of the specified genes. If set to 2, RPGeNet will also retrieve parents and childs to the interactors of the input genes. Please, note that this field can only be changed when Interaction Level is set to Skeleton.
Color the genes in the graph according to their expression in the specified experiment.
The logo image is a button to return to the home page.
This option defines three different behaviours when clicking on Nodes or Edges. "Show Properties" will display an overlay with information about the gene or the interaction. "Node Addition" will add all the interactors to the clicked node to the visualization. Finally, "Node Deletion" will delete the clicked node from the visualization; please, not that this process is irreversible.
Change the layout of the nodes and interactions. Available layouts are: 'Dagre', 'Cose', 'Grid', 'Circle', and 'Concentric'.
This button will add all the interactions in the current level between all the genes displayed on the visualization.
This button will remove all the nodes that are currently not connected in the graph display.
Increase or decrease the border size of genes.
Increase or decrease the border size of genes.
The roots of the RPGeNet network begin with the driver genes of retinitis pigmentosa. All driver genes are purple borders. Some driver genes are associated with syndromic genetic disorders and are square shaped within the network explorer. Non-syndromic driver genes are diamond shaped. Driver genes that are syndromic and non-syndromic are star shaped.
Non-driver nodes are all circular and have borders that indicate the level, where the gene is found within the network, by the color.
The arrows that connect nodes within the network are color-coded to indicate whether they are physical, genetic or unknown interactions.
All nodes, driver and non-driver genes, have a colored interior that represents their expression depending on the expression data used. Absolute expression is the raw expression within the retina. The RET-ALL option is the relative expression within the retina in comparison with all 32 tissues of the microarray experiment. The RET-OTHER is the relative expression within the retina in comparison with all the tissues minus the retina.
Pathway to Level allows you to get the shortest paths between a specified Gene and either 'Driver Genes' or 'Skeleton Genes'. If there is more than one target gene with the same path length (the same number of interactions until reaching that gene), all the pathways will be displayed on the results page.
Pathway to level is useful when trying to assess the importance of a particular gene to Retinitis Pigmentosa, or to have an idea of how close a gene is to other genes related to Retinitis Pigmentosa (in terms of signalling and protein pathways).
As can be seen in the image above, each pathway is represented as an individual graph visualization. Only one pathway is represented between two genes; if you want all the possible shortest pathways between, for example, PMM2 and SNRNP200, you can click on the "All shortest paths" link above the visualization. In addition, if you want to explore a particular pathway further, you can click on the "Explore Network" button, which will bring you to Network Explorer with the specified pathway in the graph visualization.
This form allows you to compute the shortest path between any two genes in the network. Please, note that all the connections in RPGeNet are directional, so the results of A->B will be different from B->A. All the shortest paths are computed on the WholeGraph. The results page from this form is the same as the one from "Pathway to Level".