## 3 Results and Discussion
### Network Visual Mining
#### 3.2.1 Visual Mining of HSPNs; The Most Central and Atypical ABFPs
This observation supports that changes in the HSPN topology by removing edges (similarity relations) not only produce sparser networks with an increased number of clusters, but also lead to a variation in peptides' centrality measures and therefore the networks' topological distribution. However, a small set made up of likely the most relevant peptides was identified for four and three centrality measures in both HSPNs. These are the cases of starPep_00048, starPep_03668, starPep_10922 and starPep_0000. These peptides seem to be very important within the ABF chemical space. The starPep_00048 is a human defensin derivative (HNP1) of 30 amino acid length, with several reported interesting bioactivities (antiviral, anti-Gram+/-, antifungal, anticancer, enzymatic inhibitor) alongside its antibiofilm action, which is probably exerted by its ability to disrupt membranes and interfere in biological processes involved in interspecies interaction [50; 51]. The starPep_03668 and starPep_10922 peptides are synthetic constructions of 35 and 12 aa length, respectively. The starPep_03668 was designed as pathogen-selective peptide, based on the fusion of a species-specific targeting peptide domain with a wide-spectrum antimicrobial peptide domain. Thus, it showed activity against several communities of _Streptococcus_ species [52]. By contrast, starPep_10922 was designed as a D-enantiomeric peptide aiming to resist proteases' degradation and also to prevent the accumulation of (p)pPGPp, which is a key messenger for biofilm formation. StarPep_10922 was able to prevent biofilm formation from _P. aeruginosa_ as well as to disperse and eradicate the bacteria in the resulting mature biofilm [53]. So far, these three central peptides have not been reported as toxic to mammalian cells, and are lead peptides for developing ABFP drugs. The peptide starPep_0000, a 26 aa length ABFP that was derived from melittin (bee venom), appears to be a promising candidate, since several pharmacological activities have been assigned to it quite apart from its antibiofilm activity; it has also been extensively evaluated against many targets [54; 55]. However, starPep_0000 has also shown haemolytic activity and toxicity to eukaryotic cells, which may limit its therapeutic potential unless its toxicity can be relieved by optimization procedures [55]. The ABFP space is not only represented by the central peptides; there also exist peptides that are disconnected from the giant component of the network and which bear low values of node degree. These peptides are categorized as atypical because they share very low sequence similarities with the central or popular ones, which prevents the estimation of their properties. However, they are remote members of the ABFP family and they also account for the antibiofilm chemical space. In this sense, the HSPN with similarity cutoff is very useful for uncovering atypical peptides. The cutoff of AF similarity at 0.65 was the optimal for retaining a reasonable trade-off between the number of communities and singletons; where the simplest community is considered to be when two nodes (peptides) are connected, and singletons are those that are not connected with any other in the network. Atypical peptides represent singular structures that may represent privilege scaffolds for designing antibiofilm agents.