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- I. Navigating the genes' knowledge chain network through NETWORK NAVIGATOR
- II. Navigating the knowledge chain in the visualized GKCN
- III. References
Navigating the genes' knowledge chain network through NETWORK NAVIGATOR
The genes' knowledge chain network (GKCN) for each SADR topic is used to define the biological linkages between all genes (1-3), which enable users to jump over the genes to systematize and create their own gene-oriented knowledge chain of a certain SADR.
There are two ways to navigate the GKCN. Taking SJS for example, one can jump from one gene to its 'neighbors' using "NETWORK NAVIGATOR" (NN) or the visualized GKCN. The navigation can begin from the gene list page in Fig. 1, where SJS-related genes are sorted by their CR values, and are presented in a Google pattern. Within each card, the relevant extended genes, if any, in GKCN are displayed, and the SJS-related literature containing this gene is displayed. Here the impact factor of the gene denotes the mean reference impact factor of the SJS-related Pubmed entries carrying this gene.
Clicking on HLA-B will lead the user to the detailed information page (Fig. 2), where SJS-related Pubmed entries carrying HLA-B will be displayed. Its neighbors in GKCN, the extended genes, are listed in the NN. Core genes are presented as gene cards with general information presented to help the user to pursue their interests.
Following the link of an extended gene (LTA) will lead the user to another NN (Fig. 3) where the 'parent' genes of LTA are displayed.
Clicking on IL4R in NN, for example, will take the user to another detailed page, where some new gene-SJS knowledge is presented (Fig. 4).
Users can jump between core and extended genes in such a way to retrieve a gene-oriented knowledge chain of SJS.
Navigating the knowledge chain in the visualized GKCN
In the case of SJS, core genes are represented as yellow diamonds, whereas extended gene LTA is represented as white circle (Fig. 5).
One can also access the detailed page of a gene from the Applet through right clicking on a particular gene to retrieve a popup link. In this example, the user has constructed a knowledge chain of "SJS - HLA-B - LTA - IL4R - SJS" extracted from GKCN. He could deduce that LTA relates to HLA-B and IL4R, two core genes that are involved in the pathogenesis of SJS (4,5), implying a putative functional linkage of this extended gene to SJS through MHC I-mediated pathways (6) or cytokine-mediated pathways (5). On the other hand, the logical connectivity of these three genes might prompt the user to conceive the hypothesis that a crosstalk between a MHC I-related pathway and a cytokine-related pathway might be mediated by LTA, which might give a systematic explanation of the pathogenesis of SJS.
References:
1. Jenssen, T.K., Laegreid, A., Komorowski, J. and Hovig, E. (2001) A literature network of human genes for high-throughput analysis of gene expression. Nat Genet, 28, 21-28.
2. Hoffmann, R. and Valencia, A. (2003) Life cycles of successful genes. Trends Genet, 19, 79-81.
3. Hoffmann, R. and Valencia, A. (2004) A gene network for navigating the literature. Nat Genet, 36, 664.
4. Hung, S.I., Chung, W.H., Liou, L.B., Chu, C.C., Lin, M., Huang, H.P., Lin, Y.L., Lan, J.L., Yang, L.C., Hong, H.S. et al. (2005) HLA-B*5801 allele as a genetic marker for severe
cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A, 102, 4134-4139.
5. Ueta, M., Sotozono, C., Inatomi, T., Kojima, K., Hamuro, J. and Kinoshita, S. (2007) Association of IL4R polymorphisms with Stevens-Johnson syndrome. J Allergy Clin Immunol,
120,1457-1459.
6. Chessman, D., Kostenko, L., Lethborg, T., Purcell, A.W., Williamson, N.A., Chen, Z., Kjer-Nielsen, L., Mifsud, N.A., Tait, B.D., Holdsworth, R. et al. (2008) Human leukocyte
antigen class I-restricted activation of CD8+ T cells provides the immunogenetic basis of a systemic drug hypersensitivity. Immunity, 28, 822-832.
