Tutorial 5: Using the Agilent Literature Search plugin

In cases where there are few measured interactions, text mining can be a useful mechanism for inferring network data. The Agilent Literature Search plugin for Cytoscape provides a flexible, interactive platform for mining text and assessing the results in a network context. Here we shall explore the use of this plugin.

This plugin searches public literature repositories such as PubMed for articles matching user-specified queries, and then builds a network based on putative associations suggested in the text of the articles. Putative associations are sentences of two or more gene or protein names, and verbs that suggest interaction such as "catalyzes", "is repressed by", or "regulates". For a description of the algorithm, see this article.

If you have completed the basic Cytoscape tutorials, in this tutorial you will:

This tutorial and accompanying lectures were delivered at CSC, the Finnish IT center for science. The lecture slides of background material and an accompanying video presentation are available courtesy of the CSC at http://www.csc.fi/english/research/sciences/bioscience/Courses_and_events/cytoscape/index_html.

Important: Public literature repositories such as PubMed are always changing. The illustrations shown here are based on the public literature databases as they existed when this document was written. At another time, after more papers have been published, the composition of the databases will change, and the exact search results will change. Consequently, your own search results will probably not look exactly like the ones shown here.

If you have not already done so, download and install Cytoscape on your local computer, following the instructions given in the Cytoscape manual.

Download and install the Agilent Literature Search plugin, as follows:

  1. Go to the plugin license page.

  2. Read the license agreement and fill out the short form below, clicking the checkbox to accept the terms of the agreement.
  3. Click on the Proceed to Download button, proceeding from there to the plugin download page.
  4. Select the installer for your platform (Windows, Mac OS X, or Linux), click on the appropriate download link, and follow the installation instructions provided via the adjacent View link.
  5. If you are currently running Cytoscape, exit.

Basic operation

  1. Start up Cytoscape. Under the Plugins menu, select Agilent Literature Search. The Agilent Literature Search Agreement will appear. Check the "Don't show this dialog again" box and click the Accept button.
  2. The following window will appear.
    • small_proxy.png

      • If you are using a proxy server to access the Internet, click Yes and enter your proxy settings. Otherwise, click No.
  3. The following window should appear.
    • small_litsearch.png

  4. In the Terms window, enter P53. The term "P53" should appear in the Query Editor, and the forward arrow just below should turn blue to indicate it is available. Click on the forward arrow to begin searching.
  5. After a brief interval, the search results should appear in two places:
    1. Under Query Matches, there should appear a numbered list of articles labeled Results, as shown below. A slider at the right side of the window allows you to scroll through the list of selected articles. Each article should be listed along with a URL, and a hyperlink for jumping directly to that URL.

      Since the number of matches was set to ten, up to ten articles will be displayed. In general, these are the most recent articles that match your search terms. If you bring up a web browser and search PubMed on the same search term (P53) you should see exactly the same matches.

      • small_query.png

    2. A network should appear on the Cytoscape canvas, showing interactions inferred from sentences in the selected articles.


In this case, the canvas shows tp53 connected directly to eight nodes, with another four connected to yy1 but not tp53. How did these other four nodes and their interactions get into a network generated by a search on P53? This is a consequence of the two-step process used by the Literature Search plugin:

Validating, refining, and saving your search results

You can explore the sentences that were selected as evidence of interaction between these nodes, as follows:

  1. Go to your Cytoscape canvas and click on some edge with your right mouse button. A menu should appear listing the interaction and listing a sub-menu labeled Evidence from Literature. This sub-menu should have four options, labeled Show Sentences from the Literature, Gather Evidence from the Literature, Extend Network from the Literature, and Highlight Search Terms.
  2. Select Show Sentences from the Literature. A window should appear, listing a number of sentences as shown:
    • small_sentences.png

  3. Recall that each of these sentences is predicted to represent an interaction between these two proteins. What if you disagree with one of these predictions? Right-click on the sentence, and a menu should appear with the option Delete Sentence. Click on the option to delete the sentence, or click elsewhere to keep it.

  4. Delete all the sentences for these two nodes. When you are done, notice that the canvas has changed: the edge between these nodes has been removed. Since this leaves the two nodes with no connections, the nodes are also deleted.

In addition to exploring individual sentences, you can explore the evidence from entire articles, as follows:

  1. Return to the Query Matches section of the Agilent Literature Search window.
  2. Right-click on the first match.
  3. A popup menu should appear with the option Delete Match. Click to remove the match to the first article, along with any interactions supported by that article only. After deleting the match, any nodes containing only edges that are supported by only that article will be deleted.
  4. If the article has a small Cytoscape logo next to the title, the right-click menu will also show the option "Highlight Match". Selecting this option will highlight the matches derived from this article on the Cytoscape canvas. The nodes should turn yellow, and the edges between them should turn red.
  5. Under the File menu of the Agilent Literature Search window, you will see options labeled Load Search Results and Save Search Results. If you want to save a set of search results for later analysis, these options will allow you to do so.

Under the Agilent Literature Search window, there are a number of basic search controls, as described here.

When performing a complex query, you should see up to ten matches per search term returned, and a larger network on the canvas such as the one shown:

Nature[ta] }}}

  1. This results in (P53) AND (Cancer OR Science[ta] OR Nature[ta]). Unfortunately, this is not quite what we want: Instead of returning articles on P53 and cancer published in the selected journals, it would return articles on P53 that either involved cancer or were published in the selected journals. So, in your query editor, revise the query to read
    • (P53) AND Cancer AND (Science[ta] OR Nature[ta])

  2. Issue your query, and explore the query results as outlined above.

Gathering Supporting Evidence

In addition to mining the literature for associations, you can use the Agilent Literature Search plugin to verify other interactions against the literature. This section illustrates how.

  1. Download BINDHumanSubset.sif to your local computer by right-clicking on the hyperlink and saving the file. This is a sample set of interactions from the BIND database provided by BOND. Important: This functionality relies on parameters defined in the last use of the Literature Search plugin, in this session of Cytoscape. If you have taken a break since the previous steps, and have just started a new Cytoscape session, then before continuing, you must do a literature search with Homo Sapiens selected as the species.

  2. Load the network BINDHumanSubset.sif. Lay out the network with the yFiles Organic layout. Your Cytoscape canvas should appear as shown:
    • small_human.png

  3. Select by name the node Sp1, and zoom in to get a closer look of the other nodes that interact with it. Your canvas should appear as shown:


  4. Right-click on the edge between Sp1 and Myc. You should see a menu containing the option Evidence from Literature. This item should take you to another menu, with the option Gather Evidence from the Literature. Select this option, and a literature search will be executed. When it is done, a message will appear at the bottom of the Cytoscape Desktop indicating if any new evidence was found.
  5. Go to the Edge Attribute Browser and click on the Select Attributes button. You should see several new attributes:
    • HasTSI: Indicates if the interaction is supported by literature searching
    • NumberOfSources: Indicates the number of distinct articles supporting the interaction

    • nbrSentences: Indicates the number of distinct sentences supporting the interaction How much support is there for this interaction?
  6. Go back to the Cytoscape Desktop, and right-click on the edge between Myc and Sp1 again. If any evidence was found in the literature for this interaction, then under Evidence from Literature, there should be a new option: Show Sentences from the Literature. Selecting this option will bring up a window listing the supporting sentences, as shown below.
    • small_support.png

  7. Exactly what was the search that generated these results? The Gather Evidence function performs a search of ten articles per search term, using the two nodes as search terms and using the species and interaction lexicon used in the last full literature search. For example, if your last full literature search was done on mouse with a relaxed interaction lexicon, then the Gather Evidence function would search for the two nodes in mouse, using a relaxed interaction lexicon.

You can also gather evidence on all the edges for a given node. For example, select the node YY1 and right-click on it. Select Gather Evidence from the Literature in the resulting menu. This will perform a literature search on all the edges of the node.

Congratulations! You have not only completed one more tutorial, but you've also learned how to use a powerful tool that is also fun to play with!

For comments or suggestions, please post to the cytoscape-discuss mailing list.

Return to the Cytoscape advanced tutorials.

Presentations/05_Literature (last edited 2009-02-12 01:03:34 by localhost)

Funding for Cytoscape is provided by a federal grant from the U.S. National Institute of General Medical Sciences (NIGMS) of the Na tional Institutes of Health (NIH) under award number GM070743-01. Corporate funding is provided through a contract from Unilever PLC.

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