It follows that microRNAs with involvement in many pathways – universe microRNAs – might be able to produce large changes within the cell, resulting in measurable outcomes compared to controls.
Curation-free biomodules classification derived from congruent gene expression activation breaks from the paradigm of recapitulating the known curated pathway mechanism universe.
The extension of our FAIME methodology with curation-free biomodules ("Cancer Module") derived from the dynamic and congruent activation and/or deactivation of gene expression across numerous cancers breaks from the paradigm of recapitulating the known curated pathway mechanism universe.
In attempts to validate this classification of microRNAs into intra-pathway and universe classes, we went to the literature.
Typically in Mr. Ritchie's work, those stories map a metaphoric pathway through the expanding universe, taken here by a single "character" in the form of an amorphous blue swath, called "The Swimmer".
In contrast, the circular genomic permutation, which is also performed at the SNP-level where the number of significant genes in the pathway and in the universe are not fixed (similarly to the SNP-level random permutations), seems to capture the genomic structure and shows how likely an outcome is expected according to this structure.
We identify two distinct classes of microRNAs, suggesting a hierarchical organization of microRNAs co-targeting genes both within and between pathways, and implying differential involvement of universe and intra-pathway microRNAs at the disease level.
Overlaying universe and intra-pathway microRNAs with the Pathways in Cancer Network built for Figure 5, we see that universe microRNAs have much higher degree than intra-pathway microRNAs in the Pathways in Cancer network (p<0.0001) (Figure 7B).
The identification of two distinct classes of microRNAs – universe and intra-pathway microRNAs – lays the frame work for possibly hierarchical organization of pathway- and gene-level control and execution of gene regulation.
Further, we have identified two novel classes of microRNAs: universe and intra-pathway microRNAs, which are significantly differentiated by the degree of their involvement in signalling pathways within the cell and their association with cancer (p<0.0001) and human disease (p<0.0001).
