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PubChem BioAssay: Link chemical research to GenBank and beyond Yanli Wang 251st American Chemical Society National Meeting San Diego, California March 13th-17th, 2016 PubChem BioAssay … • Public Data Repository at NCBI • Open Research Database • Small Molecule Bioactivity Data • RNAi Screening • Connect to PubChem Substance • Integrated with Other Biomedical Resources 2 PubChem BioAssay … support multiple research areas • Chemical Biology • Chemgenomics • Medicinal Chemistry • Drug Discovery • Functional Genomics 3 PubChem BioAssay … data standard Meta data Test results • • • • • • • • Sample ID / SID • Bioactivity outcome / score/potency/dose response • Phenotype annotation • Bioactivity readout • Cross reference • Target • Replicate • Attributes Protocol Target Cell line Comment / Categorized comment Grant number Embargo date Cross reference publication taxonomy related assays gene, nucleotide etc. PubChem BioAssay … data content Statistics • 1,000, 000 records • 3,000,000 tested substances • 220,000,000 bioactivity outcomes • 1,000,000,000 data points • 200 chemical probes Data type • HTS experiment • Literature curation • Bioactivity • Toxicity • Selectivity Profiling Links to many other databases PubMed Protein 50,000 OMIM BioSystems 10,000 a pathway db drug annotation Gene MeSH Literature claasifiication 50,000 Nucleotide Depositor website GEO Taxonomy 3000 CDD conserved protein family domain Structure a mirror of Protein Data Bank (PDB) 6 Link Research Data to Molecular Target … BioAssay targets all test results specific to test reagent specific readout 7 Chemical Probe F2RL3 antagonists IC50: 0.139 uM (CID: 2333) CHRM5 antagonists IC50: 0.44uM (CID: 42519285) mGlu5 positive allosteric Potentiator EC50: 2.411 uM (CID: 1318633) STAR inhibitor IC50: 2.12 uM (CID: 45100448) … 200 EGFR inhibitor IC50: 0.7079 uM (CID: 2303746) mGluR3 modulator IC50: 2.611 uM (CID: 60210836) more Thyroid Hormone Receptor / Steroid Receptor Coregulator 2 interaction inhibitor Potency: 1.4uM (CID: 5184800) MRGPRX1 allosteric activator EC50: 0.19 uM (CID:71598556) 8 Protein BioAssay Target … Protein class for BioAssay targets Enzyme (4399) Membrane receptor (705) Ion channel (409) Transcription factor (224) Transporter (180) Epigenetic regulator (166) Secreted protein (63) Structural protein (53) Auxiliary transport protein (32) Protein class for MLP probe targets Surface antigen (20) Adhesion (15) Other cytosolic protein (256) Other membrane protein (18) Enzyme (27) Membrane receptor (25) Other nuclear protein (18) Transporter (6) Unclassified protein (1170) Transcription factor (5) Ion channel (3) Epigenetic regulator (1) Other cytosolic protein (1) Unclassified protein (19) Biological Pathways for Protein Target … BioSystems name KEGG id (conserved pathway) Count of genes Neuroactive ligand-receptor interaction ko04080 623 Calcium signaling pathway ko04020 329 cAMP signaling pathway ko04024 299 PI3K-Akt signaling pathway ko04151 279 MAPK signaling pathway ko04010 252 Ribosome ko03010 220 Proteoglycans in cancer ko05205 194 cGMP-PKG signaling pathway ko04022 190 Focal adhesion ko04510 189 Rap1 signaling pathway ko04015 186 Oxytocin signaling pathway ko04921 181 Retrograde endocannabinoid signaling ko04723 168 Inflammatory mediator regulation of TRP channels ko04750 168 HTLV-I infection ko05166 165 Vascular smooth muscle contraction ko04270 165 Chemokine signaling pathway ko04062 163 Alzheimer's disease ko05010 161 Epstein-Barr virus infection ko05169 155 Adrenergic signaling in cardiomyocytes ko04261 155 Dopaminergic synapse ko04728 153 Organisms … Organism Assay Count Rattus norvegicus 391714 Homo sapiens 260507 Mus musculus 118398 Staphylococcus aureus 17767 Canis lupus familiaris 16884 Escherichia coli 13513 Cavia porcellus 12341 Human immunodeficiency virus 1 9075 Pseudomonas aeruginosa 6654 Oryctolagus cuniculus 6574 Candida albicans 6206 Bos taurus 5277 Plasmodium falciparum 5037 Macaca mulatta 4412 Streptococcus pneumoniae 3604 Mycobacterium tuberculosis 3562 Macaca fascicularis 3244 Klebsiella pneumoniae 3031 Saccharomyces cerevisiae 2900 Cricetulus griseus 2889 Gene Target and its relevance to disease … Linking Gene target to MedGene 3000 2500 2000 1500 1000 500 0 BioAssay Descriptions & Data … https://pubchem.ncbi.nlm.nih.gov/bioassay/1202 A RNAi BioAssay Record… http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=720703 Gene target Kinase selectivity profiling assay… BioAssay Search … - classification tool for research data https://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi BioAssay Target Search … Link BioAssay data to Entrez Gene … Identify drugs Verify gene & chemical functions with modulators RNAi data 18 Summary • Repository of chemistry & functional genomics research data • Cross link chemical biology data to genomic resources providing access to chemical tools • Identify gene functions • Predict target and off-targets • Evaluate selectivity, promiscuity, toxicity • Construct drug target network • Drug repositioning PubChem … Open & Public Resource http://pubchem.ncbi.nlm.nih.gov Send questions to: [email protected] [email protected] [email protected] Acknowledgement Steve Bryant Evan Bolton Ben Shoemaker Jie Chen Paul Thiessen Tiejun Cheng Jiyao Wang Gang Fu Bo Yu Haehnke Volker Jian Zhang Lewis Geer Renata Geer Asta Gindulyte Lianyi Han Jane He Siqian He Sunghwan Kim