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In addition to our observation that the modules identified using the graph partitioning approach were related to foldons, we had also been able to identify residues critical for folding [19].
In order to test our two contentions, namely, that the modules identified using our procedure correspond to foldons and that residues that act as connector hubs are protected early in transition phase and hence are more stable, we took recourse to molecular dynamics (MD) simulations by studying the unfolding of ubiquitin.
The three modules identified using
All the other analyses presented below were based on the RMP modules identified by applying Tc = 1.5 and Tg = 3.0 (Actually, the modules identified using other parameters showed similar results regarding the interspecies differences, but these modules were not suitable for the analysis of evolutionary pattern due to their limited number).
The most highly connected gene within each transcription modules identified using average linkage hierarchical clustering.
We showed that majority of identified modules have significant functional and transcriptional enrichment, higher than that observed in modules identified using only a single type of genomic data.
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Additional file 1: Additional tables referenced in the text as well as the reaction composition of each module identified using ShReD-based partitioning of the Hepatonet1 liver network.
While the miRmR module (comprising miR-15, miR-16 and miR-195) identified using the timecourse data set had 84 mRNAs, the module identified using the Gutierrez et al. data set had 35 mRNAs.
Network modules were identified using spectral clustering and Pathway Enrichment computed for each module using the Reactome FI plugin functions.
To confirm whether or not the two modules in the CCA network have distinct functions, the enriched molecular functions (MFs), biological processes (BPs), and cellular components (CCs) for genes in the two modules were identified using the DAVID software [23] and setting all cancer genes in the two modules as the background population.
All the tissue-related modules were identified using the ISA algorithm proposed by Bergmann et al. [20] which over-performs many traditional clustering approaches in two main aspects: 1) the modules identified by ISA are highly self-consistent; 2) the genes within a module are allowed to be involved in alternative modules [19].
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