Navigating links between structures and papers: PubMed-to-PubChem connectivity between the IUPHAR/BPS Guide to PHARMACOLOGY and British Journal of Pharmacology A poster presented at Pharmacology 2017, London, December 2017

1. 3. PubChem < > PubMed < > BJP
2. GtoPdb ligand -to-journal mappings
6. References
Deanery of Biomedical Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK.
www.guidetopharmacology.org enquiries@guidetopharmacology.org @GuidetoPHARM
Navigating links between structures and papers:
PubMed-to-PubChem connectivity between the IUPHAR/BPS
Guide to PHARMACOLOGY and British Journal of Pharmacology
Supported by:
We especially thank all contributors, collaborators and NC-IUPHAR members
1. Introduction
The pharmacological literature connects activity data reported for drugs and
research compounds to their explicit chemical structures. However, the traditional
entombing of these relationships for millions of compounds among millions of PDFs
is retrospectively acknowledged as massively problematic. The situation is
ameliorated by a range of resources that extract the entity and data relationships the
authors put “in” to the PDFs back “out” into structured database records. The
IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb) has been doing this for over a
decade by expert curation of structures, activity data and targets [1]. Our cross-
reference total has reached 30,000 with an approximately equal split between
citations related to targets or associated with ligand interactions [2]. As a
collaboration, we have been submitting ligand related citations to PubChem (PC)
who then link these into PubMed (PM). This means pharmacologists can navigate
from our GtoPdb ligand entries “out” via the PubMed Identifier (PMID) and either the
PC Substance Identifiers (SIDs that are unique to us as a submitter) or Compound
Identifiers (CIDs that merge all submitters). This work outlines our linking process in
general and for the British Journal of Pharmacology (BJP) in particular.
There are multiple sources and different contexts of PC < > PM links [3]. Data
contributors provide chemical information extracted from the scientific literature through
manual curation or data mining. Table 1 summarises the top-4 contributors by the count
of depositor-provided cross-references between PC SIDs and PMIDs.
Table 1 (adapted from [3])
While GtoPdb ranks 3rd for the manually curated contributors we have the highest
stringency of target-ligand-PMID links. Note that the 14.3 K encompasses all the papers
represented by our complete Figure 1 list. Our own analysis drilled down to selected
individual journals. The results generated for BJP are shown below.
Table 2
The interpretation of all rows in Table 2 cannot be expanded here. However, the
GtoPdb SID counts (blue) establish we are the main contributor of BJP links in recent
years and for key compounds (i.e. what those publications are “about”) back to 2010.
We extract approximately 10% of BJP papers by our criteria for database records.
Figure 1. Examples of various kinase database tables
1. Harding SD, et al. (2018) The IUPHAR/BPS Guide to PHARMACOLOGY in 2018: Updates and expansion to encompass
the new Guide to IMMUNOPHARMACOLOGY. Nucl. Acids Res. 46 (Database Issue). doi: 10.1093/nar/gkx1121.
2. https://blog.guidetopharmacology.org/2017/10/18/gtopdb-nar-database-issue-2018-journal-to-database-connectivity-and-
journal-to-gtopdb-links/
3. Kim S. et al. (2016) Literature information in PubChem: associations between PubChem records and scientific articles. J
Cheminformatics. 8:32. doi: 10.1186/s13321-016-0142-6
4. McGrath JC et al (2015) BJP is linking articles to the IUPHAR/BPS Guide to PHARMACOLOGY. BJP, 172(12):2929-32.
GtoPdb is an ELIXIR UK node resource
4. Virtuous circle: BJP < > GtoPdb < >PubChem < > PubMed
This section illustrates how linkage navigation can be followed from our entry for
PXS4728A. This is retrievable from the GtoPdb search box as ligand 9346. Our
PubChem entry is SID 328083448 and the BJP paper is PMID: 27495192. The series
of connections that users can simply click on are shown below in Figure 2.
The navigation in Fig.2. can be explained as a series of steps;
1. From the GtoPdb ligand entry (A) clicking the “Reference” goes to across to PM and
the BJP abstract (B).
2. The abstract facet (C) shows “Related Information” that includes links to PC SIDs
and CIDs.
3. Clicking on the Substance link takes users to our SID entry. Going down to
“Depositor Comments” (D) displays the same information we curated into the
summary part of the GtoPdb ligand entry.
4. The “Depositor Supplied PubMed Citations” section of the SID (E) indicates the two
references. In this case J. Med. Chem. is our primary reference and the BJP paper a
secondary reference.
5. These links are reciprocal so users can navigate into the circle via any of them.
Christopher Southan, Elena Faccenda, Joanna L. Sharman, Simon D. Harding, Adam J. Pawson, Jamie A. Davies
5. Conclusions
• Traversing publications and bioactive chemistry databases is becoming a core
competence for pharmacologists and should thus be part of their education.
• For PC as the major source of links, understanding the different types is daunting.
• However, we show in Fig 2 that, starting from GtoPdb as an easy to use entry
point, users can simply click-navigate between PM and PC in an informative
virtuous circle
• For the example shown, both BJP and the article authors will benefit from user traffic
through these links
• As featured in [3] GtoPdb is a major contributor of curated links to key bioactive
structures inside PC not just for the BJP but all journals curated by us
• However, Table 2 shows PC connections for BJP papers are complex
• We have identified specificity issues for non-GtoPdb chemistry linking sources in PC
including for the automated extraction of abstracts via IBM patent processing
• Note our curated GtoPdb > BJP linking is complemented by the BJP > GtoPdb out-
links added since 2015 and recently converted to in-line links [4]
The PMIDs we link to ligands are
predominantly what we term
primary references, selected for
curation because they include
the quantitative in vitro activity
against target proteins along with
the specification of ligand
structures, generally related to
drug R&D. We also capture what
we term secondary papers that
specify in vivo activities (e.g.
rodent data) and in fewer cases
also tertiary references as clinical
reports. Figure 1 shows the
journal distribution of ligand
associated references. While J
Med. Chem. tops the primary
citations BJP is 6th with a mixture
of primary and secondary
papers.
´
Figure 1. Top-20 Journals for ligand citations
Figure 2. The arrows and highlighted
sections indicate inter-database links
(A)
(B)
(C)
(D)
(E)