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The proposed methods allow researchers to identify clusters of pathways sharing similar functions.
Hierarchically clustering the bipartite matrix, we observed two large clusters of pathways as well as 2 large clusters of miRs.
The clusters of pathways were identified and the related pathways were ranked by their dysfunctional scores.
Networks of such correlations often lead to clusters of pathways although their interpretation is not straightforward (Chi et al., 2008).
In the second article, we identified and described seven key clusters of pathways relevant to globalization's influence on SDH.
Genetic interactions were enriched within the clusters of pathways by a factor of 5.5, confirming the organisation of our pathway network is biologically significant.
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In multivariate analyses, genomic clusters of pathway deregulation illustrate prognostic value.
This was further confirmed in a multivariate analysis of clinico-pathologic variables and genomic clusters of pathway deregulation.
Although unique clusters of pathway deregulation are representative of distinct phenotypes of breast cancer survival, the purpose of our analysis was not to generate yet another prognostic strategy.
As a proof-of-principle, we then utilized genomic clusters of pathway deregulation (as described in Figures 1 and 2) and evaluated the likelihood of sensitivity by cytotoxic agent.
Additionally, negative ER status (HR 1.47, p = 0.25), higher grade tumors (HR 1.62, p = 0.13), positive lymph node status (HR 1.66, p = 0.10) and genomic clusters of pathway deregulation (HR 2.22, p = 0.10) remained in the model suggesting prognostic values of these variables.
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