Retrospective entity linking from the literature: IUPHAR allostery review

Many of you will have noticed a gradual blurring of the distinction between publications and databases. One manifestation of this is “live linking” where entities within the text of an open access manuscript connect directly to the URL of an extrinsic database record, typically a bioactive chemical structure or a protein entry. This facilitates seamless paper < > database navigation and is complemented by paper < > paper connectivity via live-linked references. Our own engagement arose from our collaboration with the BJP and Wiley for exactly this type of markup. The results can be seen in the CGTP 2013/14 series and most recently for the NC-IUPHAR review on epigenetic pathways  where a table format is used to display target and ligand links from the publication to their corresponding entries in our database.

Given the success of this, the curation team considered the possibility of being able to do this retrospectively i.e. for any relevant article that included entities potentially linkable to GtoPdb but that had no mark-up at publication time. This post describes what we came up with.

The step of listing our URLs on our blog was obvious, since we do this anyway. Less obvious perhaps, was to use the new PubMed Commons to “cross-point” interested readers between an article and our local mark-up. However, since we were already using this to spread the word about our BJP marked-up articles (since the availability of the linking is not flagged in PubMed or Europe PubMed Central), the logical connection was there.

Since it had a particularly high density of relevant entities, we chose a recent NC-IUPHAR review on allosteric ligands for our try-out. This was published in  Pharmacological Reviews, which does not currently support internal linking of entities to external resources. We hope you find our listing below a useful supplement to the open access article, particularly to explore expanded relationships (e.g. ligands to other targets, or vice versa, find simillar ligands etc). These entities already existed as expert-curated entries in our database, either with interaction data or mentions in comments sections on our target pages. Note that in the publication these ligands appear within the text or tables.

CP55940 (2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-5-(2-methyloctan-2-yl)phenol
McN-A-343 (4-[[[(3-chlorophenyl)amino]carbonyl]oxy]-N,N,N-trimethyl-2-butyn-1-aminium chloride
THRX160209 (4-{N-[7-(3-(S)-(1-carbamoyl-1,1-diphenylmethyl)pyrrolidin-1-yl)hept-1-yl]-N-(n-propyl)amino}-1-(2,6-dimethoxybenzyl)piperidine
LY2033298 (3-amino-5-chloro-N-cyclopropyl-6-methoxy-4-methyl-thieno[2,3-b]pyridine-2-carboxamide
CP376395 (N-(1-ethylpropyl)-3,6-dimethyl-2-(2,4,6-trimethylphenoxy)-4-pyridinamine hydrochloride
PNU-120596 (N-(5-chloro-2,4-dimethoxyphenyl)-N′-(5-methyl-3-isoxazolyl)-urea
LY2087101 (2-[(4-fluorophenyl)amino]-4-methyl-5-thiazolyl]-3-thienylmethanone
xanomeline maraviroc
plerixafor 17β-estradiol tamoxifen
rosiglitazone GABA CGP7930
glutamate CPCCOEt ADX-47273
MPEP morphine ticagrelor
cocaine diltiazem ethanol
charybdotoxin tetraethylammonium ivermectin
verapamil ω-agatoxin IVA ω-conotoxin GVIA
astemizole dofetilide tetrodotoxin
batrachotoxin saxitoxin 3,3,5-triiodothyroacetic acid
tretinoin GW0072 oxotremorine-M
alcuronium cinacalcet diazepam
strychnine gallamine glycine
picrotoxin aniracetam cyclothiazide
flumazenil ketamine FGF-1
IL-1β pertuzumab trastuzumab
GS39783 etomidate propofol
ifenprodil rapamycin FITM
galantamine iperoxo amlodipine
desflurane flurazepam gevokizumab
zopiclone hanatoxin

The following ligands from the article are new entries in the database

CX614 (2H,3H,6aH-pyrrolidino(2,1-3′,2′)1,3-oxazino(6′,5′-5,4)benzo(e)1,4-dioxan-10-one
TCN-201 (3-chloro-4-fluoro-N-[4-[[2-(phenylcarbonyl)hydrazino]
SSR1281129E (sodium 2-amino-5-(1-methoxy-2-methylindolizine-3-carbonyl)benzoate
Org27569 (5-chloro-3-ethyl-N-(4-(piperidin-1-yl)phenethyl)-1H-indole-2-carboxamide) CGP13501
bisphenol A andarine

A number of targets were also detailed in the paper, at which the ligands act allosterically. The table of links below directs readers to the corresponding entries on our database. The nomenclature used in the table is the same as in the publication.

GluN1 nicotinic acetylcholine receptor GABAA receptor
Glycine receptors 5-HT3 receptors M2 muscarinic receptor
α7nAChR Ca2+ (Cav) channels Kv channels
K+ channel encoded by the human ether-à-go-go (hERG) gene CHG and HCN channels KCa channels
TRPV1 channel TRPM8 TRP channels
Nav channels Muscarinic acetylcholine receptors A1 adenosine receptor subtype
corticotrophin releasing factor-1 receptor calcitonin receptor glucagon-like peptide receptor
δ-opioid receptor FGF receptor family HER2 receptor
Abl mitogen-activated protein kinase kinase, protein kinase B (AKT) insulin-like growth factor 1 receptor
hepatocyte nuclear factor 4α homodimer CCK1 receptor CXCR2

Contributed by Chris Southan and Helen Benson

P.S. It was interesting to see that PubMed Commons picked us up for a highlight


Posted in Technical

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