The Integration of Chemistry with Everything Else

ACS National Meeting , August 2020Ian Wetherbee, Lutz Weber, Evan Bolton, Vihang Mehta, Stephen Boyer, Jane Frommer

Contributions directed toward the identification, organization and FAIR availability of the world's molecular content

Previously at ACS San Diego...

Google Patents

Patent corpusGoogle Scholar Google Books

computer curation processes

Google Patents

Worldwide patent corpus

~ 50 Billion mentions of scientific entities

New today:Donating annotated data to the public

Google Translate

computer curation processes

Google BigQueryDataset

NIH

Other

SciWalker

(Your application)

DataCC BY 4.0

“Google Patents Research Data” by Google, based on data provided by IFI CLAIMS Patent Services and OntoChem, is licensed under a Creative Commons Attribution 4.0 International License.

Natural language processing

Name to structure

Image to structure

Map to ontology

Table# of rows 47,676,364,297publication_number ocid preferred_name domainsourceconfidencecharacter_offset_startcharacter_offset_endinchiinchi_keysmiles

Schema

Data

count distinct domain samples

14,187,900,687 8,512 substances Fluoxastrobin|ougon|Sulfosulfuron

6,245,936,990 6,935 methods electrochemical analysis|ultrasonication|slugging

4,863,317,264 10,770 effects pro-activator|glycemic|vasopressic

3,891,972,531 13,629,554 chemCompound sulfur|3-(3-methoxypropoxy)propan-1-ol|Iprindole

1,921,140,121 20,124 inorgmatTc alloys|Ferromolybdenum|Li[Ni1/3Co1/3Mn1/3]O2 (NCM 111)

1,711,449,095 2,652,600 chemGroup stabilizer|1,1,1-trifluoroethane|3-pyrrolidinyl group

1,636,858,964 5,996 polymers4-(hydroxymethyl)-1,3-dioxolan-2-one|dodecyl group|NoRC associated RNA

1,376,553,092 571,320 chemClass α-D-xylose|Pyrylium salt|Isophorone

1,364,950,542 141,500 proteins GLP1R family|C1QT3 family|Amphiregulin

1,167,892,259 10,704 nutritionPteridium aquilinum subsp pseudocaudatum|vanilla syrup|Basella

1,074,276,820 108,928 humangenes AP3D1|IARS|EHD4

936,819,010 2,668 anatomyMegakaryocytes|Neurofibrillary Tangles|Satellite Cells, Skeletal Muscle

906,061,800 29,624 drugs Guanine|atovaquone|aminoxytriphene

835,712,433 199,070 species Geotrichum candidum|Nezara|Abutilon

696,195,364 22,159 diseasesFibromyalgia|Social avoidant behaviour|Adenocarcinoma pancreas

271,303,308 8,808 natprod Vinblastine|Physagulin M|Indol-3-propionic acid

73,346,722 936 toxicity aquatic toxicology|Ames test|ribotoxic

42,923,635 26,160,939 chem

N1(*)*N2C(C1=O)C(C(c1c2nc(Nc2**c*c2)nc1)(*)*)(*)*|C(N(I)CC)([C](#N)CCCCCCCC)CCC(=*)*|OC(=O)[C@]1(C[C@@H](C(*)C(C2(C(C2)C(C)CC)[C@@H](CO)O)O1)C)F

Google Patents extracts data from both text & images

Table# of rows 47,676,364,297publication_number ocid preferred_name domainsourceconfidencecharacter_offset_startcharacter_offset_endinchiinchi_keysmiles

Data

count distinct domain source

3,891,972,531 13,629,554 chemCompoundtitle,abstract,claims,description

1,711,449,095 2,652,600 chemGrouptitle,abstract,claims,description

1,376,553,092 571,320 chemClasstitle,abstract,claims,description

21,291,227 14,912,387 chem pdf *16,987,431 11,183,893 chem image *

4,644,977 2,711,658 chem mol

* still processing

Total number of chemistry entities

extracted 36 full text countries Data

country_code description claims abstract pdf * image * title mol Grand Total

US 1,409,208,212 145,488,707 10,651,425 6,504,233 6,640,303 1,425,365 4,644,977 1,584,563,222

JP 1,059,614,185 93,795,657 14,312,034 3,136,333 3,051,411 1,319,277 1,175,228,897

CN 880,335,706 130,838,122 25,630,032 1,869,214 1,180,255 2,573,546 1,042,426,875

EP 680,356,821 87,966,443 5,377,765 1,595,481 1,972,898 840,088 778,109,496

WO 522,361,876 71,891,448 4,733,108 2,332,337 2,367,645 537,893 604,224,307

KR 445,605,239 49,543,964 5,263,342 1,299,386 1,118,158 516,001 503,346,090

CA 292,648,762 45,117,787 2,855,808 1,196,171 431,672 342,250,200

AU 258,294,420 46,518,099 441,824 1,224,705 193,271 327,160 306,999,479

TW 173,408,881 19,402,002 1,259,332 947,090 51,152 144,676 195,213,133

DE 78,908,305 11,580,392 1,213,910 162,209 460,756 92,325,572

ES 65,087,386 7,723,456 2,081,943 269,099 38,847 141,399 75,342,130

RU 41,438,558 11,637,908 2,211,258 151,414 169,750 146,552 55,755,440

HU 29,630,553 4,311,374 375,805 104,216 68,077 34,490,025

BR 26,326,881 3,065,815 658,663 103,517 26,257 144,139 30,325,272

GB 17,906,597 3,136,854 6,741,940 40,357 532 299,648 28,125,928

FR 21,874,630 3,797,415 672,698 53,555 13,107 154,800 26,566,205

CZ 18,422,163 3,750,093 247,458 65,715 25,433 22,510,862

DK 19,854,711 1,309,738 22,895 96,009 144 84,597 21,368,094

EA 14,802,787 1,759,257 336,897 86,134 27,593 17,012,668

PT 14,069,417 1,881,382 73,238 48,035 48,439 16,120,511

SK 10,616,113 2,204,289 128,483 35,653 13,119 12,997,657

FI 8,985,958 1,029,199 24,540 26,695 40 33,119 10,099,551

SU 5,638,012 1,197,129 410,553 7,567 90,371 7,343,632

CH 5,229,765 902,985 107,427 14,020 13 19,554 6,273,764

DD 4,547,354 742,071 183,256 12,317 17,961 5,502,959

NL 4,386,277 728,270 72,673 9,146 372 35,251 5,231,989

BG 3,142,521 665,065 66,290 14,842 9,970 3,898,688

CS 3,131,663 486,895 127,412 7,119 23,594 3,776,683

OA 2,938,019 627,075 68,314 13,236 4,853 3,651,497

AT 1,567,123 282,784 19,963 2,250 5 101,882 1,974,007

RO 1,439,864 233,016 107,070 5,079 14,563 1,799,592

BE 1,453,407 233,066 45,029 3,660 931 10,387 1,746,480

SI 899,347 274,808 19,133 3,729 14,236 1,211,253

LU 806,646 160,527 3,934 1,978 131 3,614 976,830

LV 588,528 124,227 9,173 5,151 2,177 729,256

AP 551,743 94,321 6,079 1,792 5,036 658,971

MX 485,287 65,869 551,156

LT 449,403 82,608 10,841 1,455 4,008 548,315

Start OCID End OCID Domain Sub-domain229910000000 229914999999 chem inorganic materials229915000000 229915999999 chem alloys229920000000 229929999999 chem polymers229930000000 229939999999 chem natural products229940000000 229969999999 chem drugs239000000000 239999999999 chem substances       200000000000 209999999999 diseases main200000000000 200999999999 diseases diseases::OIS201000000000 201999999999 diseases diseases::hdo202000000000 202999999999 diseases diseases::icd9203000000000 203999999999 diseases diseases::icd10204000000000 204999999999 diseases diseases::snomed205000000000 205999999999 diseases diseases::elsevier206000000000 206999999999 diseases diseases::MedDRA208999000000 208999999999 diseases diseases::MeSH209000000000 209999999999 diseases diseases::syno_ocids

Table

# of rows 47, 571, 142, 272publication_number ocid preferred_name domainsourceconfidencecharacter_offset_startcharacter_offset_endinchiinchi_keysmiles

OCID : a unique identifier for every entity

OCIDs provided by OntoChem

Data

Website

● Easy to use● Limited feature

scope/breadth● Limit to

configurability/extensibility

Publication

Patent

Compound

Disease

Clinical trial

Assay

Classification

Target

Side effect

Entity graph

Previously at ACS San Diego...

Database

● More complex configuration (uploading, maintenance)

● Private data, other data outside of scope

Dataset scopeGoogle BigQuery

Confidential + Proprietary

Project 2

Project 1

SQL interface1 TB query free / month

10 GB storage free / month

Google BigQuery

No server setupAnalyze, download results

A single huge, relational database

Compound -> MW, LogP, etc.

Patent -> Compound, Target

Patent -> Company, Class, Text, etc.

ACLs

etc.

Compound -> Toxicity

Example of use in cloudBigQuery

1,074 patents in the D06M15/00 patent classification mention perfluorooctanoic acid

Example of use in webPubChem

PubChem is a chemical information resource

• 100s of data fields about chemicals

• Biological activities• Programmatic access interfaces• FTP site for bulk downloads• Extensive integration with

chemistry-related websites

• Millions of monthly users

https://pubchem.ncbi.nlm.nih.gov

https://pubchem.ncbi.nlm.nih.gov/

Google Patent contribution to PubChem

• +45B CSV rows available on the PubChem FTP site ‘as-is’

• +16K gzip compressed CSV files (subdirectories each with up to 1000 files)

• +4TB content uncompressed

• Structures via SMILES added to PubChem Substance (+9M)

• Association of patent to structure (billions of links)

Google Patent contribution to PubChem

• +45B CSV rows available on the PubChem FTP site ‘as-is’

• +16K gzip compressed CSV files (subdirectories each with up to 1000 files)

• +4TB content uncompressed

• Structures via SMILES added to PubChem Substance (+9M)

• Association of patent to structure (billions of links) Accessible via:

https://ftp.ncbi.nlm.nih.gov/pubchem/Other/GooglePatents/ftp://ftp.ncbi.nlm.nih.gov/pubchem/Other/GooglePatents/

https://ftp.ncbi.nlm.nih.gov/pubchem/Other/GooglePatents/ftp://ftp.ncbi.nlm.nih.gov/pubchem/Other/GooglePatents/

Google Patent contribution to PubChem

• +45B CSV rows available on the PubChem FTP site ‘as-is’

• +16K gzip compressed CSV files (subdirectories each with up to 1000 files)

• +4TB content uncompressed

• Structures via SMILES added to PubChem Substance (+9M)

• Association of patent to structure (billions of links)

1•• Extract SMILES

2•• Add as PubChem

Substance records

3•• Associate patent

identifiers to records

Processing of Google Patent contribution

Google Patent contribution to PubChem

• To be integrated with other patent links within PubChem

• Searchable collection• Patent section of compounds• Accessible by programmatic interfaces• Downloadable per record• Associated to metadata about a given

patent

}aid_sid_cid_acname_acvalue_aidname243,326,686

30.2 GBaidsidcidacnameacvalueaidname

SQL in BQ

SELECT distinct(acname), count(acname) as count_acn FROM `ncbi-research-pubchem.pubchem.aid_sid_cid_acname_acvalue_aidname` GROUP BY acnameORDER BY count_acn DESC

acname count_acnPotency 51,654,071IC50 12,947,417EC50 2,664,101Ki 559,067IC90 334,633AC50 209,578GI50 132,714Kd 88,048CC50 75,027MIC 64,718LC50 38,073TGI 33,396Activity 27,139AbsAC40_uM 21,374ED50 16,745LD50 3,018

‘starting material’ = PubChem tables ‘reagents’ = SQL query

product = answers to queries

ExampleWhat types of assays are in PubChem ?

partial list

} 554.3 MB processed, could run ~1800 times (= 1TB) per month for free

}

Kaggle +

ExampleWhat compounds have assays for targets MDM2, MEK, KRAS, & IL17?

Ass

ay #

, lo

gAssay type

Assay Counts by Target

Free Python notebooks

5TB / month free BQ quota

Acknowledgements We would like to acknowledge our colleagues who help make this work possible.

● Vihang Mehta

● Robert Frommer

● Brodrick Arneson

● Stephen S. Walker

● Igor Filippov

● Members of the OntoChem team

● The Intramural Research Program of the National Library of Medicine, National Institutes of Health.

● The entire PubChem team and all PubChem contributors and collaborators

Thank you!

BigQuery: "Google Patents Public Datasets"patents-public-data.google_patents_research.publications

PubChem download: https://ftp.ncbi.nlm.nih.gov/pubchem/Other/GooglePatents/

Google Patents: patents.google.comPubChem: pubchem.ncbi.nlm.nih.govSciWalker: www.sciwalker.com

Backup

This Kaggle Script will query PubChem to answer the following question:What bio assay data is available for a specific target or list of targets? e.g. MDM2,MEK, KRAS,IL17. etc.

Example

Pubchem ChemBlTarget Central

EPA

Clinical Trials

FDA Medline Drug Central

~ 250 tables from ~ 15 dbs

cluster

machine-learning

AI

visualization

post processing

How the data are used

Kaggle + BQ

aid_sid_cid_acname_acvalue_aidname243326686aidsidcidacnameacvalueaidnameinchikeysmiles

How many molecules have EC50 assays for SGLT2 ? What are they ?

or Kaggle Table 1

Answer: 143 unique molecules 20 duplicate compounds

output

SELECT cid, acname, acvalue, aidname FROM `google.com:skb1-228101.NIH_Data.PUBCHEM_AID_CID_SMILES_EC50_Data` WHERE acname = 'EC50' AND UPPER(aidname) LIKE '%SGLT2%'

Example

Kaggle in BQ+

Results for 3,443 assays for MDM2

Output file opened with DataWarrior

Example

Biomarkers co-occurring in the same document or clinical trial

Most frequently mentioned pairs of biomarkers within the same document

Example

Opportunities for partners

Google

• Patents• Scholar• Books

BigQuery

Middleware

to be developed

Front end

Integrity

GWAS

PMCMedLine COSMIC

Patents

Text sources Databases

Your Applications

Data Studio

Client Data

Looker

Knime

Other

Open Data

Example