Using a Novel Ontology to Inform the Discovery of Therapeutic Peptides from Animal Venoms

Abstract

Venoms and venom-derived compounds constitute a rich and largely unexplored source of potentially therapeutic compounds. To facilitate biomedical research, it is necessary to design a robust informatics infrastructure that will allow semantic computation of venom concepts in a standardized, consistent manner. We have designed an ontology of venom-related concepts - named Venom Ontology - that reuses an existing public data source: UniProt's Tox-Prot database. In addition to describing the ontology and its construction, we have performed three separate case studies demonstrating its utility: (1) An exploration of venom peptide similarity networks within specific genera; (2) A broad overview of the distribution of available data among common taxonomic groups spanning the known tree of life; and (3) An analysis of the distribution of venom complexity across those same taxonomic groups. Venom Ontology is publicly available on BioPortal at http://bioportal.bioontology.org/ontologies/CU-VO.

Figure 1.

A schematic diagram of classes and class relationships in the Venom Ontology. Blue arrows denote “is_a ” relationships, while other colors denote object property relationships. Diagram automatically generated by the Protégé plugin “OBO Graph View”.

Figure 2.

Two sequence similarity networks for venom peptides within the same genus. a.) shows peptides from species in genus Loxosceles, and b.) shows peptides from species in genus Bungarus. Relative node size is based on the degree of the node, and length of the edges is based on the inverse BLASTp score (see eq. (1)). Nodes of the same color are peptides from the same species of animal. Red arrows indicate “clusters” with high species diversity (i.e., similar peptides found in a number of closely related species).

Figure 3.

Violin plots showing distributions of venom complexity in 7 common taxonomic groups. Numeric summary statistics are listed in Table 2 for each of the groups shown. Complexity is measured as the number of venom peptides in Venom Ontology for a single species — the vertical axis is the complexity measure for a given species, and the widths of individual plots correspond to the density of the distribution at that complexity measure. Individual species are shown as transparent dots — they are spread horizontally (“jittered”) to better visualize dense groups of data points.