Evidence mapPaperPMID 30002366Full record

ArticleNature communications2018

Network-based approach to prediction and population-based validation of in silico drug repurposing.

Feixiong Cheng, Rishi J Desai, Diane E Handy, Ruisheng Wang, Sebastian Schneeweiss, Albert-László Barabási, Joseph Loscalzo

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 279 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
279citing papers in PubMed, 1 pooled it
23.5field-weighted citation impact, top 1% of its field
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

279 citing papers in PubMed, 1 synthesis or guideline pooled it, 558 citations in OpenAlex.

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219 more citing papers are in PubMed but not listed here.

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

7 authors at 2 institutions in 2 countries.

Feixiong ChengCenter for Complex Networks Research and Department of Physics, Northeastern University, Boston, MA, 02115, USA.
Rishi J DesaiDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.ORCID http://orcid.org/0000-0003-0299-7273
Diane E HandyDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Ruisheng WangDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Sebastian SchneeweissDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Albert-László BarabásiCenter for Complex Networks Research and Department of Physics, Northeastern University, Boston, MA, 02115, USA.
Joseph LoscalzoDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. jloscalzo@rics.bwh.harvard.edu.
Brigham and Women's Hospital · USNortheastern University · US

Funding

NHGRI NIH HHS P50 HG004233NHGRI NIH HHS U01 HG001715NHGRI NIH HHS U01 HG007690NHGRI NIH HHS U41 HG001715NHLBI NIH HHS K99 HL138272NHLBI NIH HHS P01 HL083069NHLBI NIH HHS R37 HL061795NHLBI NIH HHS RC2 HL101543NHLBI NIH HHS U01 HL108630NIGMS NIH HHS P50 GM107618Patient-Centered Outcomes Research Institute (PCORI) ME-1303-5638U.S. Department of Health & Human Services | National Institutes of Health (NIH) GM 107618U.S. Department of Health & Human Services | National Institutes of Health (NIH) HG007690U.S. Department of Health & Human Services | National Institutes of Health (NIH) HL016795U.S. Department of Health & Human Services | National Institutes of Health (NIH) HL106373U.S. Department of Health & Human Services | National Institutes of Health (NIH) HL108630
6 · The paper itself

Abstract

Here we identify hundreds of new drug-disease associations for over 900 FDA-approved drugs by quantifying the network proximity of disease genes and drug targets in the human (protein-protein) interactome. We select four network-predicted associations to test their causal relationship using large healthcare databases with over 220 million patients and state-of-the-art pharmacoepidemiologic analyses. Using propensity score matching, two of four network-based predictions are validated in patient-level data: carbamazepine is associated with an increased risk of coronary artery disease (CAD) [hazard ratio (HR) 1.56, 95% confidence interval (CI) 1.12-2.18], and hydroxychloroquine is associated with a decreased risk of CAD (HR 0.76, 95% CI 0.59-0.97). In vitro experiments show that hydroxychloroquine attenuates pro-inflammatory cytokine-mediated activation in human aortic endothelial cells, supporting mechanistically its potential beneficial effect in CAD. In summary, we demonstrate that a unique integration of protein-protein interaction network proximity and large-scale patient-level longitudinal data complemented by mechanistic in vitro studies can facilitate drug repurposing.

Indexed as

Computer SimulationCarbamazepineCoronary Artery DiseaseDatabases, FactualDrug RepositioningHumansHydroxychloroquinePrognosisPropensity ScoreProportional Hazards ModelsProtein Interaction MapsReproducibility of ResultsRisk AssessmentRisk FactorsCarbamazepineHydroxychloroquine

Identifiers

PMID30002366
PMCPMC6043492
OpenAlexW2826750344

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.