Fig 4. Variation in functional annotation enrichment with increasing tightness between the predicted targets and the ECCN.

The significance of 28 enriched GO terms (A) and 16 KEGG terms (B) for genes connected to the CCN steadily decreases for most terms as the minimum number connections is increased (this number of connections between a gene and a gene set is here defined as "tightness"). As the minimum tightness between the predicted targets and the ECCN increases, the enrichment and rank of functional annotation changes. We observe an overall decrease in enrichment but little in rank. The greatest changes in rank occur between a tightness of 2 and 3. At a tightness of two and above, the rank of the majority of significant GO terms such as "mitotic cell cycle" and "nuclear mRNA splicing, via spliceosome", and KEGG terms such as "Spliceosome", "Ubiquitin mediated proteolysis" and "RNA degradation" remain largely stable suggesting a natural threshold on tightness at this point.