1. 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

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. Chemical Probe … 200 more F2RL3 antagonists IC50: 0.139 uM (CID: 2333)
mGlu5 positive
allosteric
Potentiator
EC50: uM
(CID: )
EGFR inhibitor
IC50: uM
(CID: )
Thyroid Hormone Receptor /
Steroid Receptor Coregulator 2
interaction inhibitor
Potency: 1.4uM
(CID: )
*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: )
STAR inhibitor
IC50: 2.12 uM
(CID: )
mGluR3 modulator
IC50: uM
(CID: )
MRGPRX1
allosteric activator
EC50: 0.19 uM
(CID: )

9. Protein BioAssay Target …

10. 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

11. 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

12. Gene Target and its relevance to disease …

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

14. A RNAi BioAssay Record… http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=720703
Gene target

15. Kinase selectivity profiling assay…

16. BioAssay Search … classification tool for research data

17. BioAssay Target Search …

18. Link BioAssay data to Entrez Gene …
Verify gene functions with RNAi data
Identify drugs & chemical modulators

19. 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

20. PubChem … Open & Public Resource http://pubchem.ncbi.nlm.nih.gov
Send questions to:

21. 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