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Association Analysis for Large-Scale Gene Set Data 27b. From DAG: press ENRICHED DAG (opens new window) and press one of theDAG boxes, containing the interesting GO category.c. By GO category keyword (might yield many or none gene sets): type a keyword (e.g., “neuron” or “development”) in the box above KEY WORD SEARCHand press KEY WORD SEARCH button. This opens a new window with multiplecategories, each showing the genes that were contained in the initial geneset (brain embryo imprint).d. From GO category identifier: type the GO category name (e.g., “neuron differentiation”)in the box above GO TERM SEARCH and press the button. Unlikethe previous method (step 7c) this search will produce one or zero (if there isno intersection between the category and the initial gene set or if the category isnot correctly identified) gene sets.As shown in Fig. 1, there is strong association between the input gene set andseveral categories, most notably neuron development and nervous systemdevelopment. Discovering all of these associations manually would have beenextremely difficult.3.4. Pathway Association AnalysisSome of the tools in Table 1 can be used for finding associations among genesets and known biological pathways. The primary sources of data for this analysisare KEGG and BioCarta. One exception is the PANTHER analysis tools, whichare supported by their own database. The general considerations when choosingthe appropriate tool are similar to GO analysis tools.There are three steps: (1) uploading the gene set, (2) selecting (or uploading)a reference gene set, and (3) performing the analysis.1. Retrieve the “lymph node” gene set as in Subheading 3.1.2.2.2. Press the BioCarta or KEGG button.3. Select a reference set by choosing “human” (all genes in the human genome).4. At this point, a list of pathways is available. Pathways with a desired p-value(default value of 0.01) are highlighted in red. Clicking the name of the pathwayswill cause redirection to the source website (KEGG or BioCarta) and display thepathway maps. Genes from the original gene set are highlighted in the KEGGpathway map.5. Export/Save the image (see Fig. 2).3.5. Other Types of Associative AnalysisOther associations also could be of some value. Among these are proteindomains, genome reference into function, and Pubmed. The associationanalysis for this type of data is performed in the same way as the pathwayanalysis in WebGestalt (see Subheading 3.4.), after pressing the correspondingbutton.

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