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Target Discovery and Validation Reviews and Protocols

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50 Imoto et al.<br />

Fig. 9. (continued)<br />

From the Monte Carlo simulations in Tamada et al. (13), this method succeeded<br />

in identifying the target drug-affected genes <strong>and</strong> pathways with the high coverage<br />

greater than 80%.<br />

3.3.2. Application of Time-Exp<strong>and</strong>ed Network Method<br />

From the gene–gene relationships of 735 genes estimated in Subheading<br />

3.2.4., we performed the time-exp<strong>and</strong>ed network method to extract drug-active<br />

pathways of the drug griseofulvin. We used the time-course microarray data of<br />

dosing 50 mg/mL, i.e., we used five microarrays corresponding to 0, 15, 30, 45,<br />

<strong>and</strong> 60 min. Figure 9A shows the identified drug-active pathways in the gene<br />

network estimated in Subheading 3.2.4. The identified drug-active pathways<br />

are colored red.<br />

The identified drug-active pathways are extracted as subnetworks shown in<br />

Fig. 9B. Note that we focus on the subnetworks from the root genes up to the<br />

third descendants. In these drug-active pathways, only nine distinct genes listed

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