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Genome Biol
2009 Jan 01;104:R44. doi: 10.1186/gb-2009-10-4-r44.
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Choosing the right path: enhancement of biologically relevant sets of genes or proteins using pathway structure.
Thomas R
,
Gohlke JM
,
Stopper GF
,
Parham FM
,
Portier CJ
.
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A method is proposed that finds enriched pathways relevant to a studied condition using the measured molecular data and also the structural information of the pathway viewed as a network of nodes and edges. Tests are performed using simulated data and genomic data sets and the method is compared to two existing approaches. The analysis provided demonstrates the method proposed is very competitive with the current approaches and also provides biologically relevant results.
Figure 1. Empirical distribution function of number of pathways associated with genes at given distances from terminal nodes. Empirical cumulative distribution function of the number of pathways that are associated with genes that have gene products located at a given distance, d (= 0, 1, 2, 3, 4), from a terminal node of the pathway network. Gene products that are at a distance d = 0 are the terminal gene products. The data used were those of all the genes associated with human signaling pathways in the KEGG pathway database [44].
Figure 2. Receiver-operator characteristic and positive predictive power versus negative predictive power plots for lung cancer data. (a) Sensitivity versus '1 - specificity' of enriched pathways that are predictive of survival from lung cancer for four methods: SEPEA_NT1, SEPEA_NT1*, GSEA and maxmean. SEPEA_NT1* is the same analysis as SEPEA_NT1 except that the pathway network information was not used. (b) Positive predictive power (ppp) versus negative predictive power (npp) for the same data and using the same methods of analysis as in (a).
Figure 3. Schematic of networks used to generate simulated data. Illustrative schematic of the two pathways used to generate the simulated data. (a) The Linear network of 30 nodes/gene products, each of which is associated with one gene. The pair of squiggly lines across some arrows is used to indicate that there are more nodes that are not shown. (b) The Erbb signaling pathway from the KEGG pathway database [44]. The expressions of the genes associated with the nodes circled in red are correlated with each other and are the genes that were affected by the treatment.
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