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Poster PubMed-to-PubChem connectivity between GtoPdb and BJP

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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

Published in: Science
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Poster PubMed-to-PubChem connectivity between GtoPdb and BJP

  1. 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)

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