ChemProt-2.0: visual navigation in a disease chemical biology database

Abstract

ChemProt-2.0 (http://www.cbs.dtu.dk/services/ChemProt-2.0) is a public available compilation of multiple chemical-protein annotation resources integrated with diseases and clinical outcomes information. The database has been updated to >1.15 million compounds with 5.32 millions bioactivity measurements for 15 290 proteins. Each protein is linked to quality-scored human protein-protein interactions data based on more than half a million interactions, for studying diseases and biological outcomes (diseases, pathways and GO terms) through protein complexes. In ChemProt-2.0, therapeutic effects as well as adverse drug reactions have been integrated allowing for suggesting proteins associated to clinical outcomes. New chemical structure fingerprints were computed based on the similarity ensemble approach. Protein sequence similarity search was also integrated to evaluate the promiscuity of proteins, which can help in the prediction of off-target effects. Finally, the database was integrated into a visual interface that enables navigation of the pharmacological space for small molecules. Filtering options were included in order to facilitate and to guide dynamic search of specific queries.

Figure 1.

A workflow of the functionalities in ChemProt-2.0 is depicted. User can query ChemProt-2.0 using chemical, protein, disease, ATC code and SEs. Outcomes from the query are represented with the arrows.

Figure 2.

Example of the graphical interface output based on a compound query. On the top, user can specify the query using the display settings. The heatmap on the left represents the bioactivities gathered for the input compound (in blue) and structurally similar compounds (in pink) in the X-axis and the proteins in the Y-axis. A color spectrum from blue (low) to red (high) is used to represent the activity. If several binding data have been measured for the same chemical–protein interaction, intensity of the colors is represented inside the circle. It is shown for example for the dopamine transporter (Q63380). The heatmap on the right describes the disease categories annotated to a protein. The value inside the circle represents the number of diseases associated to a protein.

Figure 3.

Example of the disease complexes network representation for the dopamine receptor D2 (DRD2). Twenty-five proteins interact directly to the protein DRD2 and pointing the cursor to ‘Schizophrenia’, seven genes are associated to this disease.