Transgenic mice for the IGF-I pathway, over-expressing IGF-I, IGF-IR, or IRS1 and IRS2 in the mammary gland, all develop breast adenocarcinomas [ 12, 13, 48, 49].
As seen in the PSA parameter rankings in Figure 6 and following the insights offered by the iPSA in Figure 7, the effect of perturbing early response processes, including type-I pathway, was integrated over time in the PSA.
Although, there are diagnostic platforms who can investigate EGFR mutations using just 3 cells, this does not allow the investigation of other molecular pathway over-expressions [9].
Axon guidance was the other major pathway over-represented in our enrichment analysis.
In parallel, an independent pathway over-representation analysis was also performed using the GeneSpring program.
Gene Ontology and pathway over-representation analysis yielded many of the same pathways and processes as did the earlier analysis of the complete geneset; however the involvement of the type I IFN pathway in the H5N1 response became more evident.
The significance value for pathway over-representation was calculated using a right-tailed Fisher's exact test.
To determine the common and distinct pathways to which these genes aligned, we performed pathway over-representation analysis with the tool GO-Elite (Figures 7C E).
GO and pathway over-representation analysis as well as further analysis of protein:protein and other interactions and were carried out using the InnateDB platform (http://www.innatedb.ca) [17].
Gene Ontology and pathway over-representation analysis was then performed on this subset of genes, as well as the 49 genes differentially expressed in response to H5N1 only.
Because each cluster may contain genes involved in a common molecular pathway, over-represented KEGG pathways for each cluster were identified using the log-odds ratio (see Methods).
