PubChem BioAssay – Connecting chemical genomics and genomic information resources at NCBI Yanli Wang Biocuration 2015 Beijing, China April 25, 2015 Battle against disease … No sharing Data was locked in 3 PubChem … http://pubchem.ncbi.nlm.nih.gov Small molecule and RNAi Three connected databases … A public resource providing chemical structures and comprehensive information on the biological activities of small molecules and other reagents including RNAi PubChem goals • a public repository for molecular structures and bioassay data • integrate information from various sources to provide value added annotation • develop data search, analysis, and retrieval tools to facilitate the use of chemical structures and bioactivity results 9 PubChem history: the MLI initiative (http://mli.nih.gov/mli/ 2004-2014) • • • identify and develop small-molecule chemical probes through highthroughput screening (HTS) expand the use of chemical probes for basic research (e.g. understanding the unknown biological systems, rare diseases) all data must be deposited into PubChem to be public Science, 2004, 306:1138-1139 14 PubChem: go beyond the MLI 300 sources for substance 60 sources for bioassay 16 MLI sources academic institution (Broad Institute, Harvard U., John Hopkins U.) government agency (FDA, EPA, NCATS, NIAID, NIST) pharmaceutical company (Sigma-Aldrich, GlaxoSmithKline, Abbott) journal publisher (Nature Publishing Group, Web of Science) database provider (DrugBank, ChEMBL, KEGG, SureChem, NMRShiftDB) other See full list at: http://pubchem.ncbi.nlm.nih.gov/sources/ 15 PubChem is a community hub PubChem Growth … - Substances & Chemical Structure PubChem Growth … - BioAssay Data Entries (AID count) 1,000,000 bioassay records HTS experiment Chemical biology research Medicinal chemistry study Toxicology Literature based data Selectivity profiling Physicochemical property profiling Small Molecule RNAi Literature Based BioAssay Data Content – Data from 54,000 publications Journal Name Number of unique Pubmed ID (pmid) Number of BioAssay records (AID) Journal of medicinal chemistry 17516 319947 Bioorganic & medicinal chemistry 15313 166466 Journal of natural products 5438 41378 Bioorganic & medicinal chemistry 4954 67392 European journal of medicinal 3192 51580 2125 67750 The Journal of biological chemistry 179 3410 Nature chemical biology 171 6559 ACS medicinal chemistry letters 155 2524 Proceedings of the National Academy 117 4154 99 663 Science (New York, N.Y.) 17 970 Nature 14 501 letters chemistry Antimicrobial agents and chemotherapy of Sciences of the United States of America The Journal of pharmacology and experimental therapeutics Literature Based BioAssay Data Content – RNAi screens Journal Name Number of unique Pubmed ID (pmid) Number of BioAssay records (AID) Nature 4 5 Science (New York, N.Y.) 4 4 Proceedings of the National Academy 3 3 Nature cell biology 3 3 Genes & development 2 2 Molecular cell 2 2 Cancer research 1 2 Science signaling 1 1 The Journal of biological chemistry 1 1 The Journal of cell biology 1 1 Genome research 1 1 Nature genetics 1 1 Journal of cell science 1 2 Molecular biology of the cell 1 1 PLoS genetics 1 1 of Sciences of the United States of America Growth In PubChem Usage PubChem Usage PubChem links to many other databases PubMed Protein a literature db OMIM BioSystems a pathway db Gene MeSH Nucleotide Depositor links GEO Taxonomy CDD a conserved domain db Structure a mirror of Protein Data Bank (PDB) 25 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) Surface antigen (20) Adhesion (15) Other cytosolic protein (256) Other membrane protein (18) Other nuclear protein (18) Unclassified protein (1170) Protein class for MLP probe targets Enzyme (27) Membrane receptor (25) Transporter (6) 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 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 more EGFR inhibitor IC50: 0.7079 uM (CID: 2303746) mGluR3 modulator IC50: 2.611 uM (CID: 60210836) Thyroid Hormone Receptor / Steroid Receptor Coregulator 2 interaction inhibitor Potency: 1.4uM (CID: 5184800) MRGPRX1 allosteric activator EC50: 0.19 uM (CID:71598556) 30 A Small Molecule BioAssay Record… http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=1284 BioAssay Descriptions & Data … http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=1284 BioAssay Target … http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=1284 A RNAi BioAssay Record… http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=720703 Gene target PubChem Search http://PubChem.ncbi.nlm.nih.gov/ http://www.ncbi.nlm.nih.gov/ 37 BioAssay search by target name 39 BioAssay from NCBI Protein search GI , accession, UniProt 40 BioAssay from NCBI Gene search Select RNAi data 41 BioAssay tool: related bioassays Assays related by target 43 Upload screening results • • • • • Spreadsheet load File or web Include all test results E.g. an article table Auto-validations On-hold Record Flexibility • Time the public release of your data • Satisfy journals and funding agencies • Receive PubChem Ids up-front • Create View Keys to privately share URLs with collaborators • Keep data on-hold as long as necessary 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
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