Database Commons

a catalog of worldwide biological databases

ChemProt is a publicly available compilation of chemical-protein-disease annotation resources that enables the study of systems pharmacology for a small molecule across multiple layers of complexity from molecular to clinical levels. In this third version, ChemProt has been updated to more than 1.7 million compounds with 7.8 million bioactivity measurements for 19,504 proteins. Here, we report the implementation of global pharmacological heatmap, supporting a user-friendly navigation of chemogenomics space. This facilitates the visualization and selection of chemicals that share similar structural properties. In addition, the user has the possibility to search by compound, target, pathway, disease and clinical effect. Genetic variations associated to target proteins were integrated, making it possible to plan pharmacogenetic studies and to suggest human response variability to drug. Finally, Quantitative Structure-Activity Relationship models for 850 proteins having sufficient data were implemented, enabling secondary pharmacological profiling predictions from molecular structure. Database URL: http://potentia.cbs.dtu.dk/ChemProt/. © The Author(s) 2016. Published by Oxford University Press.

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.

Systems pharmacology is an emergent area that studies drug action across multiple scales of complexity, from molecular and cellular to tissue and organism levels. There is a critical need to develop network-based approaches to integrate the growing body of chemical biology knowledge with network biology. Here, we report ChemProt, a disease chemical biology database, which is based on a compilation of multiple chemical-protein annotation resources, as well as disease-associated protein-protein interactions (PPIs). We assembled more than 700,000 unique chemicals with biological annotation for 30,578 proteins. We gathered over 2-million chemical-protein interactions, which were integrated in a quality scored human PPI network of 428,429 interactions. The PPI network layer allows for studying disease and tissue specificity through each protein complex. ChemProt can assist in the in silico evaluation of environmental chemicals, natural products and approved drugs, as well as the selection of new compounds based on their activity profile against most known biological targets, including those related to adverse drug events. Results from the disease chemical biology database associate citalopram, an antidepressant, with osteogenesis imperfect and leukemia and bisphenol A, an endocrine disruptor, with certain types of cancer, respectively. The server can be accessed at http://www.cbs.dtu.dk/services/ChemProt/.