Abundance of high throughput target oriented and high content phenotypical screens are deposited at PubChem. According to PubChem data model the results of the screens are reduced to Active (i.e. compound producing effect at reasonably low concentrations) vs. Inactive compounds.

Figure 1. PHENOTHERA data

PHENOTHERA: intergrating target oriented assays

PHENOTHERA integrates target oriented screens: for protein targets being screened active compounds are selected. In total, more than 300 proteins are covered with at least 100 active molecules. The number of active molecules varied significantly across different targets. In total, more than half million unique molecules are covered. Active molecules also split into inhibitors, activators, .. if such information has been provided in PubChem.

Figure 2. PHENOTHERA: intergrating target oriented assays

PHENOTHERA: intergrating target oriented assays

In the next step of data integration, PHENOTHERA unite active molecules in the groups if the corresponding targets belong to the same pathway (Reactome) or functional group (Gene Ontology). Thus, molecules targeting pathway or GO term are formed.

Figure 3. PHENOTHERA: creating sets of molecules targeting pathway/GO term

Phenotypical screens : in vivo desease models

On the other hand - in about 200 high content phenotypical screens reports active vs. inactive molecules for libraries covering from 10 000 to 500 000 compounds. Many BioAssays model important disease related or toxic conditions.

Figure 4. PHENOTHERA: Phenotypical screens

PHENOTHERA: inference of enriched targets or pathways for a phenotypic screen

PHENOTHERA is using standard enrichment analyses to link protein/pathway/GO term with a phenotypical Bioassay. Enrichment among molecules known to target protein/pathway/GO term is indicative that protein/pathway/GO term could represent therapeutic target for the treatment of modeled conditions (By BioAssay). In this case, we directly observe in the data that targeting protein/pathway/GO term increases chances for a molecule to produce desired effect.

Figure 5. PHENOTHERA: linking Target/Pathway to Phenotypical Bioassay (compound enrichment principle)