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To fulfill this goal, we employed the significantly changed genes by each compound that have been known to be associated with liver function to build gene networks based on Ingenuity knowledge base.
Ingenuity network modeling based on "Ingenuity Knowledge" database prioritized five significant gene networks with score ≥ 32.
* Expression of the respective gene is known to be regulated by IL1, TNF, IL6, and/or IRF7 (based on Ingenuity Knowledge Database).
IPA analyzes various bioinformatics tools including functional annotation, clustering, and network discovery based on Ingenuity Knowledge Base, which is the core technology of all IPA systems and the p-value developed from Right-tailed Fisher's exact test were mainly considered to interpret the interaction and functions of the differentially expressed genes [ 85, 86].
* bold letters, part of a network connected by the IPA relationship "Expression" (Fig 3B) ** bold numbers, fc > 1.5, p < 0.005 *** italic number, fc > 1.5, p > 0.005 NC, No change fc < 1.5 **** Expression of the respective gene is known to be regulated by IL1, TNF, IL6, and/or IRF7 (based on Ingenuity Knowledge Database).
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Gene function interpretation was based on Ingenuity Pathway Analysis (IPA, Ingenuity Systems).
* ) Annotation based on Ingenuity Pathway Analysis ® by Ingenuity Systems.
Gene networks were constructed based on the Ingenuity knowledge base.
The criteria are based on the ingenuity knowledge base and on our statistical filters as described above.
IPA is a software used to connect molecules based on the Ingenuity Knowledge Base, its database of information on biomolecules and their relationships [ 19].
Core analysis was performed in IPA using significantly expressed genes from the statistical analysis based on the Ingenuity Knowledge Base with the reference set "Genes + Endogenous Chemicals".
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