Evidence map›Paper›PMID 29876834›Full record

ArticleDrug safety2018

Predicting Adverse Drug Effects from Literature- and Database-Mined Assertions.

Mary K La, Alexander Sedykh, Denis Fourches, Eugene Muratov, Alexander Tropsha

Abstract read
In one paragraph

Article in Drug safety, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Mary K LaDivision of Practice Advancement and Clinical Education, UNC Eshelman School of Pharmacy, 301 Pharmacy Lane, Chapel Hill, NC, 27599, USA.
Alexander SedykhLaboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, 301 Pharmacy Lane, Chapel Hill, NC, 27599, USA.
Denis FourchesDepartment of Chemistry, North Carolina State University, Raleigh, NC, 27695, USA.
Eugene MuratovLaboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, 301 Pharmacy Lane, Chapel Hill, NC, 27599, USA.
Alexander TropshaLaboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, 301 Pharmacy Lane, Chapel Hill, NC, 27599, USA. alex_tropsha@unc.edu.ORCID 0000-0003-3802-8896

Funding

Drug Repurposing for Cancer Therapy: From Man to Molecules to ManU01CA207160 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI TROPSHA, ALEXANDER · 2016 to 2018
$1.2M
NCI NIH HHS U01 CA207160NIH HHS 1U01CA207160
6 · The paper itself

Abstract

introductionGiven that adverse drug effects (ADEs) have led to post-market patient harm and subsequent drug withdrawal, failure of candidate agents in the drug development process, and other negative outcomes, it is essential to attempt to forecast ADEs and other relevant drug-target-effect relationships as early as possible. Current pharmacologic data sources, providing multiple complementary perspectives on the drug-target-effect paradigm, can be integrated to facilitate the inference of relationships between these entities.

objectiveThis study aims to identify both existing and unknown relationships between chemicals (C), protein targets (T), and ADEs (E) based on evidence in the literature. MATERIALS AND

methodsCheminformatics and data mining approaches were employed to integrate and analyze publicly available clinical pharmacology data and literature assertions interrelating drugs, targets, and ADEs. Based on these assertions, a C-T-E relationship knowledge base was developed. Known pairwise relationships between chemicals, targets, and ADEs were collected from several pharmacological and biomedical data sources. These relationships were curated and integrated according to Swanson's paradigm to form C-T-E triangles. Missing C-E edges were then inferred as C-E relationships.

resultsUnreported associations between drugs, targets, and ADEs were inferred, and inferences were prioritized as testable hypotheses. Several C-E inferences, including testosterone → myocardial infarction, were identified using inferences based on the literature sources published prior to confirmatory case reports. Timestamping approaches confirmed the predictive ability of this inference strategy on a larger scale.

conclusionsThe presented workflow, based on free-access databases and an association-based inference scheme, provided novel C-E relationships that have been validated post hoc in case reports. With refinement of prioritization schemes for the generated C-E inferences, this workflow may provide an effective computational method for the early detection of potential drug candidate ADEs that can be followed by targeted experimental investigations.

Indexed as

Databases, FactualData MiningDrug-Related Side Effects and Adverse ReactionsHumansPrescription DrugsProteinsPrescription DrugsProteins

Identifiers

PMID29876834
PMCPMC6212308

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.