Chemical Database

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D1388–D1395 Nucleic Acids Research, 2021, Vol. 49, Database issue
doi: 10.1093/nar/gkaa971
Published online 5 November 2020
PubChem in 2021: new data content and improved
web interfaces
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Department
of Health and Human Services, Bethesda, MD, 20894, USA
Received September 14, 2020; Revised October 06, 2020; Editorial Decision October 08, 2020; Accepted October 11, 2020
ABSTRACT
PubChem (https://pubchem.ncbi.nlm.nih.gov) is a
popular chemical information resource that serves
the scientific community as well as the general
public, with millions of unique users per month.
In the past two years, PubChem made substantial improvements. Data from more than 100 new
data sources were added to PubChem, including
chemical-literature links from Thieme Chemistry,
chemical and physical property links from SpringerMaterials, and patent links from the World Intellectual
Properties Organization (WIPO). PubChem’s homepage and individual record pages were updated to
help users find desired information faster. This update involved a data model change for the data objects used by these pages as well as by programmatic
users. Several new services were introduced, including the PubChem Periodic Table and Element pages,
Pathway pages, and Knowledge panels. Additionally,
in response to the coronavirus disease 2019 (COVID19) outbreak, PubChem created a special data collection that contains PubChem data related to COVID-19
and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
INTRODUCTION
PubChem (https://pubchem.ncbi.nlm.nih.gov) (1–4) is a
public chemical database at the National Library of
Medicine (NLM), an institute within the U.S. National Institutes of Health (NIH). It collects chemical information
from more than 750 data sources and disseminates it to the
public free of charge. With more than four million unique
interactive users per month at peak time (see Figure 1),
PubChem is one of the most visited chemistry web sites
in the world. PubChem serves as a key chemical informa-
tion resource for biomedical research communities in many
areas such as cheminformatics, chemical biology, medicinal chemistry and drug discovery. Importantly, PubChem is
widely used as a ‘big data’ source in machine learning and
data science studies for virtual screening (5–9), drug repurposing (10–13), chemical toxicity prediction (14–16), drug
side effect prediction (17,18) and metabolite identification
(19–22) and so on.
PubChem organizes its data into three databases (2): Substance, Compound and BioAssay. The Substance database
is a repository where depositor-provided chemical data are
archived. The Compound database stores unique chemical structures extracted from the Substance database. The
BioAssay database stores biological assay descriptions and
test results. For each record in these databases, PubChem
provides a dedicated web page that presents its available data. In addition, PubChem also provides alternative views through web pages that present the data related to a specific gene, protein, pathway, and patent (examples of these pages are listed in Table 1). PubChem
data can be downloaded interactively through web interfaces or programmatically through several web service access routes including PUG-REST (23,24) and PUG-View
(25).
As a public resource used by millions of users with diverse backgrounds, it is challenging for PubChem to satisfy the data needs of all users. For example, PubChem
needs to efficiently handle large amounts of heterogeneous
data collected from hundreds of data sources in various
scientific domains, while simultaneously striving to limit
data errors and handle important scientific data representation nuances. An increase in mobile users raises the
need for responsive webpages that are rendered appropriately on both large screens (e.g. desktops) and small
screens (e.g. tablets and smartphones). To address these
and other challenges, many changes have been made to
PubChem since our latest update paper published in this
journal (1).
* To whom correspondence should be addressed. Tel: +1 301 451 1811; Fax: +1 301 480 4559; Email: bolton@ncbi.nlm.nih.gov
Published by Oxford University Press on behalf of Nucleic Acids Research 2020.
This work is written by (a) US Government employee(s) and is in the public domain in the US.
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Sunghwan Kim , Jie Chen , Tiejun Cheng , Asta Gindulyte , Jia He , Siqian He ,
Qingliang Li , Benjamin A. Shoemaker , Paul A. Thiessen , Bo Yu , Leonid Zaslavsky ,
Jian Zhang and Evan E. Bolton *
Nucleic Acids Research, 2021, Vol. 49, Database issue D1389
Chemical-literature links
DATA CONTENTS
With data integration from over 100 new sources for the
past two years, PubChem now contains more than 293 million depositor-provided substance descriptions, 111 million
unique chemical structures, and 271 million bioactivity data
points from 1.2 million biological assays experiments (as
of August 2020). This corresponds to an increase in substances, compounds and bioactivities by 19%, 14% and
14%, respectively, compared to the statistics reported in our
previous paper two years ago (1). This section highlights
some of the notable new data added to PubChem.
COVID-19 data set
The coronavirus disease 2019 (COVID-19) outbreak (26–
28), which began in early 2020, caused a serious global
health crisis and scientific communities initiated various efforts to stop this deadly disease. This created a huge demand for convenient access to data pertinent to COVID19 and the severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2). In response to this urgent demand, PubChem created a special data collection, which contains PubChem data related to COVID-19 and SARS-CoV-2. This
COVID-19 data collection can be accessed either from the
PubChem homepage or via the following URL:
https://pubchem.ncbi.nlm.nih.gov/#query=covid-19.
The data in this collection are collected from various
authoritative sources, including several NCBI databases
(RefSeq, Gene, Protein, Structure, GenBank, ClinicalTrials.gov) (4,29,30) as well as other external resources
(UniProt (31), RCSB Protein Databank (PDB) (32),
IUPHAR/BPS Guide to PHARMACOLOGY (33),
WikiPathways (34), DrugBank (35), COVID-19 Disease
Map (https://fairdomhub.org/projects/190), CAS COVID19 Protein Target Thesaurus (https://www.cas.org/covid19-protein-target-thesaurus), European Clinical Trials
Register (https://www.clinicaltrialsregister.eu/ctr-search/
search?query=covid-19)). This data collection is updated
on a weekly basis and PubChem is actively seeking new
relevant data to add to it.
Links to molecular property data in SpringerMaterials
For >32 000 compounds, PubChem now provides links to
hundreds of chemical and physical properties pertinent to
material science and related fields, available from SpringerMaterials (https://go.usa.gov/xvqfq). The summary page of
a compound with the SpringerMaterials link has a list
of properties available at SpringerMaterials for that compound in the ‘SpringerMaterials Properties’ subsection in
the ‘Chemical and Physical Properties’ section. For example, the following link shows the list of the material properties for CID 702 (ethanol):
https://pubchem.ncbi.nlm.nih.gov/compound/
702#section=SpringerMaterials-Properties
Clicking on one of the properties in this list directs to the
SpringerMaterials web page showing a list of articles containing detailed information on that property. The SpringerMaterials links help users to locate property data and related literature available for chemicals.
Links to PATENTSCOPE at WIPO
The World Intellectual Property Organization (WIPO)
provided PubChem with >16 million chemical structures
searchable in its patent database called PATENTSCOPE
(https://go.usa.gov/xdhfK). For each chemical structure
contributed by WIPO, PubChem provides a direct link
to PATENTSCOPE, enabling PubChem users to search
PATENTSCOPE for patent documents relevant to that
chemical structure. For example, the following URL directs
users to the ‘WIPO PATENTSCOPE’ section of CID 3672
(ibuprofen):
https://pubchem.ncbi.nlm.nih.gov/compound/
3672#section=WIPO-PATENTSCOPE.
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Figure 1. Growth of the number of unique PubChem users per month, as
tracked by Google Analytics. The data shown here are for interactive users
who access PubChem through web browsers only and does not include
programmatic users.
PubChem added more than 1.35 million links between
chemicals and scientific articles that mention them, thanks
to data contributed by the publisher Thieme Chemistry
(https://go.usa.gov/xEDCA). These data contain about 745
000 chemicals, along with relevant articles and their metadata (including the digital object identifier (DOI), publication title, name of the journal or book, publication type,
language, and publication year). The summary page of each
compound contributed by Thieme Chemistry includes a
table containing document links from Thieme Chemistry,
as shown in the following example (for CID 9568614, esomeprazole):
https://pubchem.ncbi.nlm.nih.gov/compound/
9568614#section=Thieme-References
The addition of Thieme Chemistry information drastically increased the number of chemical structures in PubChem with links to the scientific literature. Of the 750 000
chemicals, >40% were new to PubChem and 90% previously lacked literature links. Importantly, because many
of these articles are about chemical synthesis, they are
often not found in PubMed, which focuses on literature
in biomedical and life sciences. Therefore, these chemicalliterature links dramatically expand the findability, accessibility, interoperability, and reusability (FAIR) of synthesisrelated chemical information.
D1390 Nucleic Acids Research, 2021, Vol. 49, Database issue
Table 1. Links to examples of the pages that present data for various types of PubChem records
Example ID
Link
Compound
CID 1983
Chemical name ‘ibuprofen’
SID 138460
AID 248
Gene ID 1956
Gene name ‘EGFR’
Accession P00533
PDB Chain ID 1XKK A
Reactome ID R-BTA-177929
US7651687
AID 248 & SID 553777
Accession P00533 & CID 5328245
Gene ID 1956 & CID 5328245
https://pubchem.ncbi.nlm.nih.gov/compound/1983
https://pubchem.ncbi.nlm.nih.gov/compound/ibuprofen
https://pubchem.ncbi.nlm.nih.gov/substance/138460
https://pubchem.ncbi.nlm.nih.gov/bioassay/248
https://pubchem.ncbi.nlm.nih.gov/gene/1956
https://pubchem.ncbi.nlm.nih.gov/gene/egfr
https://pubchem.ncbi.nlm.nih.gov/protein/P00533
https://pubchem.ncbi.nlm.nih.gov/protein/1XKK A
https://pubchem.ncbi.nlm.nih.gov/pathway/Reactome:R-BTA-177929
https://pubchem.ncbi.nlm.nih.gov/patent/US7651687
https://pubchem.ncbi.nlm.nih.gov/bioassay/248#sid=553777
https://pubchem.ncbi.nlm.nih.gov/protein/P00533#cid=5328245
https://pubchem.ncbi.nlm.nih.gov/gene/1956#cid=5328245
Substance
BioAssay
Gene
Protein
Pathway
Patent
Bioactivity
The link presented in this section allows users to search
PATENTSCOPE for patent documents relevant to ibuprofen and further analyze returned hits using the tools available at PATENTSCOPE. The integration of WIPO’s chemical information with PubChem makes it easier for PubChem users to find pertinent patent information about
chemicals.
databases, but also hits from other collections (e.g., proteins,
genes, pathways, assays, scientific articles, patents). In addition, the new search box accepts chemical structure queries,
allowing users to perform various types of structure search,
including identity, similarity, substructure and superstructure searches (Figure 3). The query structure can be provided as SMILES (45–47) or InChI strings (48) or drawn
using the PubChem Sketcher (49).
ToxNet migration
ToxNet (36) was a collection of NLM databases that provided a wide range of toxicological information. As part of
a broad reorganization at NLM, ToxNet was retired in December 2019 and PubChem is now hosting chemical toxicology information for several ToxNet databases, including
the Chemical Carcinogenesis Research Information System (CCRIS), Genetic Toxicology Data Bank (Gene-Tox)
(37,38), and Hazardous Substances Data Bank (HSDB)
(39,40). Text data from HSDB, ChemIDplus (41), LactMed
(42,43) and LiverTox (44) are integrated as annotations into
compound records in PubChem. Chemical toxicity test results of chemicals from CCRIS and Gene-Tox are archived
as bioassay records and substances tested in them. More
detailed information on the ToxNet integration into PubChem can be found at: https://pubchemdocs.ncbi.nlm.nih.
gov/toxnet.
WEB INTERFACES
Redesigned webpages
To provide users with easier access to its content, we redesigned the PubChem homepage and the pages dedicated
to individual records (e.g. compound, substance, bioassay,
gene, protein and patent) (Table 1). The new pages use responsive design that works on both desktop computers and
mobile devices like smartphones and tablets. In addition,
color-themes were introduced for different collections. For
example, compound pages have a light blue theme, while
substance pages use a yellow theme.
Importantly, the new PubChem homepage provides improved search capabilities. The new homepage has a single
search box that allows users to search multiple data collections simultaneously using a single query (Figure 2). For
example, a text query ‘glucose’ in the search box returns
not only hit chemicals from the Compound and Substance
Knowledge panels
To help users quickly find important relationships among
chemicals, genes, and diseases, we introduced knowledge
panels. They show a list of a few selected chemicals, genes, or
diseases that are most commonly mentioned together with a
given chemical or gene in scientific articles. For example, the
Compound summary page of CID 1983 (acetaminophen)
has the following three knowledge panels:
• Chemical–chemical co-occurrences: https://pubchem.
ncbi.nlm.nih.gov/compound/1983#section=ChemicalCo-Occurrences-in-Literature
• Chemical–gene co-occurrences: https://pubchem.ncbi.
nlm.nih.gov/compound/1983#section=Chemical-GeneCo-Occurrences-in-Literature
• Chemical–disease co-occurrences: https://pubchem.
ncbi.nlm.nih.gov/compound/1983#section=ChemicalDisease-Co-Occurrences-in-Literature
For each co-occurring entity listed on the knowledge
panel, a sample of relevant PubMed records is displayed as
evidence (with a link to the full set). The content displayed
in knowledge panels is generated from statistical analysis
of mentions of chemicals, genes, and diseases in PubMed
records. This analysis involves annotating PubMed records
using natural-language processing (NLP) software, called
LeadMine (50), and matching the annotations with information in PubChem and other databases. More detailed information on this co-occurrence analysis can be found at:
https://pubchemdocs.ncbi.nlm.nih.gov/knowledge-panels.
PubChem Pathway View page
The PubChem Pathway page for a given biological pathway provides information on chemicals, proteins, genes and
diseases involved in or associated with that pathway, and
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Record type
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Figure 2. Partial screen shot of the page returned from a text query ‘glucose’ (https://pubchem.ncbi.nlm.nih.gov/#query=glucose). PubChem interprets
the query and suggest the best record pertinent to the query (Box A). The new search interface allows the user to simultaneously search multiple collections
and hits returned from different collections can be viewed by click the corresponding tabs (Box B). Clicking one of the returned hits directs the user to the
page dedicated to the record (Box C). The user can perform additional tasks using the buttons available on the right column of the page (Box D).
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Figure 3. Searching PubChem using a chemical structure input. The user can provide a chemical structure query by either using a line notation (e.g. SMILES
or InChI) or by drawing the input molecule with the PubChem Sketcher (Box A). The new search interface performs different types of structure searches,
including identity, similarity, substructure and superstructure searches (Box B).
Nucleic Acids Research, 2021, Vol. 49, Database issue D1393
PubChem Periodic Table and Element pages
The PubChem Periodic Table and Element pages (61) were
introduced to help users navigate the abundant chemical elemental data within PubChem, while providing a convenient entry point to explore additional chemical content,
such as biological activities and health and safety data available in PubChem Compound pages for specific elements
and their isotopes. The Periodic Table can be accessed from
the PubChem homepage, from which Element pages for individual elements can be reached. The Periodic Table and
Element pages are also available as widgets, enabling one
to display PubChem’s element data on external web pages.
Because the widgets load data directly from PubChem, it
always shows the most current information in PubChem.
The data presented on the Periodic Table and Element
pages are integrated from scientific articles and authoritative data sources. The elemental data can be downloaded
in common file formats and imported into data analysis
programs (spreadsheet software like Microsoft Excel and
Google Sheets or computer scripts in python or R). In addition, these data are not only available through the web
interfaces but also programmatically through PUG-REST
(23,24) and PUG-View (25).
DATA MODEL CHANGE
Among the multiple programmatic access routes to PubChem data is PUG-View (25), which is a Representational
State Transfer (REST)-style interface (62,63). It serves information necessary to render interactive web pages but
also allows one to programmatically access the chemical
annotations and summary information in PubChem. In
2019, major changes were made to the data model for
JSON/XML objects returned by the PUG-View server.
More detailed information on these changes can be found
at https://go.usa.gov/xEHXj. While these changes do not directly affect web users, programmatic users need to update
the programs that retrieve and interpret data from PUG
View.
SUMMARY
The present paper describes the updates made to PubChem
over the past two years. The data integration from more
than 100 new sources to PubChem has greatly broadened
the scope of its information content. Notable additions include the chemical-literature links from Thieme Chemistry,
links to property data available from SpringerMaterials and
links to PATENTSCOPE at WIPO. In addition, a substantial amount of chemical toxicological information from several ToxNet databases has been integrated into PubChem.
These new additions significantly improved the FAIR-ness
of chemical information. It is also noteworthy that the special data collection for COVID-19 was created to provide
scientists with quick access to data critical to their efforts to
stop this deadly disease.
There were major changes to PubChem’s web interfaces.
The PubChem homepage and pages dedicated to individual records were redesigned to provide users with an easier,
mobile-friendly access to PubChem data. These changes involve a data model change for the objects used by the new
web pages as well as for programmatic users. Therefore, the
programs that retrieve and interpret data from PUG-View
should be updated accordingly.
In addition, several new services were introduced. The
new search interface allows users to search multiple data
collections within PubChem simultaneously. It also accepts
structure queries and supports different types of structure search (i.e. identity, similarity, substructure and superstructure searches). The knowledge panels, which display
chemicals, genes, or diseases most-frequently mentioned in
PubMed articles together with a given chemical or gene,
were introduced to help users quickly identify important relationships between these entities. The Pathway pages provide information on chemicals, proteins, genes, and diseases
involved in each pathway. The PubChem Periodic Table and
Element pages assist users in exploring the abundant chemical element data.
DATA AVAILABILITY
All PubChem data, tools, and services are provided to the
public free of charge.
ACKNOWLEDGEMENTS
We appreciate the hundreds of data contributors for making their data openly accessible within PubChem. Special
thanks go to the entire NCBI staff (especially to the help
desk and systems support teams).
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can be very important to provide a context to observed biological activity. All pathway records were integrated from
existing pathway resources (34,51–59) without any attempt
to merge or combine them, meaning that a pathway may
have multiple records within PubChem, with each originating from a different source. Each page for a given pathway
can be accessed via an URL of the form:
https://pubchem.ncbi.nlm.nih.gov/pathway/SOURCE:
PATHID
where SOURCE is the information source for the pathway and PATHID is the record identifier used by that
source. For instance, the following URL directs to the pathway page for the human glycolysis pathway from PathBank
(ID: SMP0000040):
https://pubchem.ncbi.nlm.nih.gov/pathway/PathBank:
SMP0000040
PubChem Pathways resource supersedes the NCBI
BioSystems database (60), which is no longer being updated. Many records in the BioSystems database are also
available via PubChem Pathways. The Pathway pages for
those records can be accessed via an URL containing NCBI
BioSystems identifiers (BSIDs), as shown in the following
example (for BSID 1458456):
https://pubchem.ncbi.nlm.nih.gov/pathway/BSID:
1458456
Chemicals, proteins, and genes presented on PubChem
Pathway pages are linked to the corresponding PubChem
pages, providing quick access to more detailed information
on these entities. In addition, the Pathway pages provide information on the interactions or reactions among these entities. The Pathway pages are searchable within PubChem
Search.
D1394 Nucleic Acids Research, 2021, Vol. 49, Database issue
FUNDING
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