PubChem BioAssay: Link chemical research to GenBank and beyond Yanli Wang PubChem BioAssay: Link chemical research to GenBank and beyond   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 *at PubChem we have several goals *public depo system *various sources

Chemical Biology Chemgenomics Medicinal Chemistry Drug Discovery PubChem BioAssay … support multiple research areas Chemical Biology Chemgenomics Medicinal Chemistry Drug Discovery Functional Genomics *at PubChem we have several goals *public depo system *various sources

PubChem BioAssay … data standard Meta data Test results Protocol Target Cell line Comment / Categorized comment Grant number Embargo date Cross reference publication taxonomy related assays gene, nucleotide etc. Sample ID / SID Bioactivity outcome / score/potency/dose response Phenotype annotation Bioactivity readout Cross reference Target Replicate Attributes

PubChem BioAssay … data content Statistics Data type 1,000, 000 records 3,000,000 tested substances 220,000,000 bioactivity outcomes 1,000,000,000 data points 200 chemical probes HTS experiment Literature curation Bioactivity Toxicity Selectivity Profiling

Links to many other databases PubMed 50,000 research data OMIM Protein 10,000 assay target BioSystems a pathway db Gene 50,000 assay target drug annotation MeSH Literature claasifiication Nucleotide assay target Depositor website *to this end *hosted by NCBI *providing additional annotation Nucleotide: AID 1637 GEO Taxonomy 3000 Structure a mirror of Protein Data Bank (PDB) CDD conserved protein family domain

Link Research Data to Molecular Target … BioAssay targets all test results specific to test reagent specific readout *at PubChem we have several goals *public depo system *various sources

Chemical Probe … 200 more F2RL3 antagonists IC50: 0.139 uM (CID: 2333) mGlu5 positive allosteric Potentiator EC50: 2.411 uM (CID: 1318633) EGFR inhibitor IC50: 0.7079 uM (CID: 2303746) Thyroid Hormone Receptor / Steroid Receptor Coregulator 2 interaction inhibitor Potency: 1.4uM (CID: 5184800) *here we show some examples of aspirin in … *generic name, brand name *same/different structure representation *but user just want one aspirin CHRM5 antagonists IC50: 0.44uM (CID: 42519285) STAR inhibitor IC50: 2.12 uM (CID: 45100448) mGluR3 modulator IC50: 2.611 uM (CID: 60210836) MRGPRX1 allosteric activator EC50: 0.19 uM (CID:71598556)

Protein BioAssay Target …

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 HTLV-I infection ko05166 165 Vascular smooth muscle contraction ko04270 Chemokine signaling pathway ko04062 163 Alzheimer's disease ko05010 161 Epstein-Barr virus infection ko05169 155 Adrenergic signaling in cardiomyocytes ko04261 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 -- assay count by Kingdom ;WITH z AS ( SELECT a.taxid, a.pTaxid AS pTaxid, 0 AS rn FROM BaTaxonomyLineage a UNION ALL SELECT z.taxid, x.pTaxid, z.rn+1 FROM z INNER JOIN BaTaxonomyLineage x ON z.pTaxid=x.taxid WHERE x.pTaxid>0 ), z2 AS ( SELECT z.taxid, z.pTaxid, ROW_NUMBER() OVER (PARTITION BY z.taxid ORDER BY z.rn DESC) AS rn FROM z ), z3 AS ( SELECT z2.taxid, y.sciName FROM z2 INNER JOIN BaTaxonomyLineage y ON y.taxid=z2.pTaxid WHERE z2.rn=1 ) SELECT z3.sciName, COUNT(DISTINCT a.aid) FROM z3 INNER JOIN BaXrefTaxon a ON a.taxid=z3.taxid GROUP BY z3.sciName SELECT TOP 20 a.taxid, COUNT(DISTINCT a.aid) cnt FROM BaXrefTaxon a GROUP BY a.taxid ORDER BY cnt DESC SELECT b.sciName, z.cnt FROM z INNER JOIN BaTaxonomyLineage b ON b.taxid=z.taxid ORDER BY z.cnt DESC

Gene Target and its relevance to disease …

BioAssay Descriptions & Data … https://pubchem. ncbi. nlm. nih

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 … Verify gene functions with RNAi data Identify drugs & chemical modulators

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: pubchem-help@ncbi.nlm.nih.gov pubchem-deposit-help@ncbi.nlm.nih.gov ywang@ncbi.nlm.nih.gov

Acknowledgement Steve Bryant Ben Shoemaker Paul Thiessen Jiyao Wang Evan Bolton Jie Chen Tiejun Cheng Gang Fu Haehnke Volker Lewis Geer Renata Geer Asta Gindulyte Lianyi Han Jane He Siqian He Sunghwan Kim Ben Shoemaker Paul Thiessen Jiyao Wang Bo Yu Jian Zhang