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30 Kirov et al.3. Gene symbols usage: gene symbols are not reliable IDs in most cases. Often differentresearch groups refer to the same gene with different gene symbols, and evenworse to different genes with the same symbol. A search for gene symbol TRAF2matches two human genes—7186 and 10010 (EntrezGene IDs). In recent yearsdifferent organizations have started the process of standardization of gene symbols(e.g., HUGO), but symbols are still unreliable and should be avoided wheneverpossible to prevent confusion and conflicts during identifier conversion.4. Database updates and gene set stability: gene annotation changes as new informationis incorporated in the publicly available databases. The process of compiling newknowledge and adding it to a database is known as “release” or “build.” WebGestaltindirectly uses many such databases through GeneKeyDB. GeneKeyDB needs tobe synchronized against each of its sources because older information in one ofthe source can create conflicts. After the update process the users’ gene sets needto be reuploaded because the identifier mapping might have changed.5. GOTM vs WebGestalt GOTree module: unlike GOTM web service, the WebGestaltGOTree module does not have its own gene set management and is dependent onthe gene sets deposited to the user WebGestalt account. Therefore, any analysiswill be lost when the analysis window is closed. The WebGestalt module is alsorestricted to include only the organisms, which are accessible through WebGestalt(currently human and mouse). Using the full GOTM service may be more appropriatein several cases.6. WebGestalt restrictions: owing to the resource limitation, GOTM and the GOTreemodule of Webgestalt current restrictions are 500. It is planned to raise the limitin the near future (besides, this would be very useful as currently the author is constantlydriven to other tools owing to this limit). Local installation of GeneKeyDBand GOTM can also provide the user with the ability to select his own limit, butdescribing the installation process for GOTM is out of the scope of this chapter.In the authors’experience GOTM/WebGestalt will work with Internet Explorer 4or higher, Mozilla (Mozilla Foundation, Mountain <strong>View</strong>, CA), Safari (Apple, Inc.,Cupertino, CA), and Konqueror (http://www.konquerer.org). If one experiences problemswith other browser, one can switch to one of these aforementioned and alert theauthors about the problem. Currently, there is no awareness of any bugs. The updatingprocess might cause some unexpected behavior because of the unexpected changein the source files (e.g., Entrez Gene), if such circumstances occur, please contact thewebmaster.Occasionally, the servers can experience difficulties with a high volume ofrequests, which will slow down the analysis considerably. Make sure the Internetconnection is not too slow and try again later, and if one observes the same problemsfor a gene set of a reasonable size, one can alert the authors directly orthrough one of the mailing lists. To check the Internet connection: Pingwww.google.com (type “ping www.google.com” in a console). Response time ofless than 120 ms and no more than 5% lost packets is sufficiently good.7. Choosing a reference data set and statistical analysis—caveats: care shouldbe taken to choose an appropriate reference data set. For example, if the whole

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