A Step-By-Step Guide to Generating Gene Interaction Networks with GeneMANIA

Amanda Birmingham (abirmingham at ucsd.edu)

The excellent network-building web tool GeneMANIA has recently been given a facelift. Its new user interface is minimal and uncluttered–so much so that it took me a little trial and error to figure out what all the buttons and options did! In case you’re in the same boat, here’s the missing manual for how to use the new-and-improved GeneMANIA website to generate a network from your gene list. (To be clear, I don’t speak for the GeneMANIA project and am not associated with it in any way–just a fan 🙂 )

  1. Before beginnning, prepare a list of the genes for which you wish to make a network. (Note that GeneMANIA accepts gene symbols or NCBI Gene IDs, but not Ensembl gene ids.) Ensure each gene identifier is on a separate line, as shown below:

  2. Visit genemania.org. The home page looks like this:

  3. If your organism of interest is not human (the default), click on the small picture of a person and select the desired organism from the resulting drop-down box:

  4. Click in the white text box with the letters “e.g.” in it . When it expands, paste the list of your genes of interest into it (to run GeneMANIA on a sample list of genes, click on the “e.g.”). Any genes that cannot be found in GeneMANIA’s database will be highlighted in red, as shown below. These genes will be ignored in the rest of the analysis, so check to ensure that they do not represent your most interesting genes!

  5. (Optional step) If you want to modify the interactions that are included in your network, click the three-dot icon next to the white text box. This displays all the interaction sources and allows you to select which should be included by checking their boxes:

  6. (Optional step) Clicking on “Customize advanced options” at the bottom of this menu provides the option to modify additional behaviors. For example, in some cases GeneMANIA defaults to adding 20 “related” genes into the network you build (determined based on the input genes’ interactions). You can change this number by sliding the slider under “Max resultant genes”.

  7. Click on the magnifying glass button to begin network creation. The magnifying glass will change to a spiral and the text box to a progress bar while the network creation is in process:

  8. The finished network will appear in the main screen. Genes with identified interactions will be connected, while those without identified interactions will be shown in a row across the bottom of the screen:

    • Genes that you input are shown with cross-hatched circles of a uniform size, while those that were added as “relevant” genes by GeneMANIA are shown with solid circles whose size is proportional to the number of interactions they have.

    • Different kinds of interactions are represented by different colored connector lines. Click on the three horizontal lines icon at the right of the screen to see the the color legend and to select or deselect which interactions are displayed:

    • Mousing over a single gene’s circle highights only its interactions:

    • Clicking on a single gene displays information about it and offers options to remove it from the network or rerun a new network analysis based on only that gene. Click the X at the top right of this info box to make it disappear when you are done with it.

    • Clicking the info button on the left of the screen shows basic information about the network, such as how many genes and interactions it includes, as well as links to the help documentation and other resources. Click again on the info button to clear it from the screen when you are done with it.

    • Clicking the pie chart button on the bottom left of the screen displays the functions associated with genes in the network and their FDR and coverage (as number of genes annotated with that function in the network versus number of genes annotated with that function in the genome):

    Checking any of the functions’ checkboxes will assign colors to those functions; once the functions list is hidden again, genes in the network image that are annotated with the chosen functions have their circles colored with the relevant colors:

    Clicking on the X next to any selected function clears its coloring from the network.

    • To move the network around the screen, click on any background space. A gray circle will appear under the mouse; drag the network to your desired position and release the mouse.

    • GeneMANIA stores your search history. To view that history, click on the circular arrow button on the bottom of the screen:

    From here, you can rerun a past search by clicking on its image, clear an individual past search by clicking on the red X at its top right corner, or clear all history by clicking on the large red button at the far left. To hide history information, click the circular arrow again.

  9. (Optional step) There are several options for modifying the on-screen layout of the network.

    • To reposition a single gene manually, simply grab that gene’s circle and drag it to where you would like it to be. To make the changed network fill up the screen again, click the diagonal arrow button on the left of the screen to reposition the modified network:
    • To redraw the network in a circular layout, click the target button on the left of the screen: . Depending on the size of your network, the re-layout may take a few moments. The resultant layout will look something like this:

    • To redraw the network in a linear layout, click the two downward arrows button on the left of the screen: . Depending on the size of your network, the re-layout may take a few moments. The resultant layout will look something like this:

    • To return to the default layout, click the intertwined arrows button on the left of the screen: . Depending on the size of your network, the re-layout may take a few moments.
  10. Once you have adjusted the network to your satisfaction, you can save it in one of several formats. These options are visible when clicking on the floppy disk button on the left of the screen:

    • Report generates and displays a PDF report of the network analysis, including the GeneMANIA software version, network image, search parameters, interaction sources searched, gene details, and interaction sources in which interactions for these genes were found. It can be downloaded from your browser window like any other PDF once generated.

    • Network image As shown downloads a jpeg of the image as currently shown on the screen.
    • Network image With plain, top labels downloads a jpeg of the network with gene labels shown above their circles rather than in them:

    • Network downloads a text file detailing the connected nodes in the network and the details of their connections:

    • Networks data downloads a text file listing the details (including citation information) for each interaction source used in the network generation:

    • Attributes data downloads a text file listing the attributes identified for each gene.

    Note that this list will be empty (except for the header line) if the Attributes checkbox is not checked in the Networks menu during set-up of the network generation:

    … or if the Max resultant attributes slider is set to zero in the Customize advanced options menu during set-up of the network generation:

    … or if there are no attributes found for the input genes in the selected Attributes sources.

    • Genes data downloads a text file with a list of all genes included in the network, as well as links to their NCBI Gene records and their GeneMANIA-assigned scores in the network:

    • Functions data downloads a text file containing functions found to be identified with genes in the network and the enrichment level of those functions (shown as FDR) based on the number of genes with that function in the network and the number of genes with that function in the genome. This list may be empty except for the header line if no such functions are identified.

    • Interactions data downloads a text file containing much the same information as the Network option but in a slightly different format:

    • Search parameters as text does not appear to function at the moment.
    • Search parameters as JSON downloads a representation of the search parameters for the network in JSON-formatted text:

  11. If you use GeneMANIA for your research, please give credit where credit is due: cite it! The appropriate citation is:

    • Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P, Franz M, Grouios C, Kazi F, Lopes CT, Maitland A, Mostafavi S, Montojo J, Shao Q, Wright G, Bader GD, Morris Q. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 2010 Jul;38(Web Server issue):W214-20. doi: 10.1093/nar/gkq537. PubMed PMID: 20576703; PubMed Central PMCID: PMC2896186.

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