Evidence map›Paper›PMID 39954672›Full record

ArticleCell reports methods2025

Exploring common mechanisms of adverse drug reactions and disease phenotypes through network-based analysis.

Farzaneh Firoozbakht, Maria Louise Elkjaer, Diane E Handy, Rui-Sheng Wang, Zoe Chervontseva, Matthias Rarey, Joseph Loscalzo, Jan Baumbach, Olga Tsoy

Abstract read
In one paragraph

Article in Cell reports methods, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
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  3. Review
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  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Farzaneh FiroozbakhtInstitute for Computational Systems Biology, University of Hamburg, Albert-Einstein-Ring 8-10, 22761 Hamburg, Germany. Electronic address: farzaneh.firoozbakht@uni-hamburg.de.
Maria Louise ElkjaerInstitute for Computational Systems Biology, University of Hamburg, Albert-Einstein-Ring 8-10, 22761 Hamburg, Germany.
Diane E HandyDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Rui-Sheng WangDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Zoe ChervontsevaInstitute for Computational Systems Biology, University of Hamburg, Albert-Einstein-Ring 8-10, 22761 Hamburg, Germany.
Matthias RareyZBH - Center for Bioinformatics, University of Hamburg, Hamburg, Germany.
Joseph LoscalzoDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Jan BaumbachInstitute for Computational Systems Biology, University of Hamburg, Albert-Einstein-Ring 8-10, 22761 Hamburg, Germany; Department of Mathematics and Computer Science, University of Southern Denmark, 5000 Odense, Denmark.
Olga TsoyInstitute for Computational Systems Biology, University of Hamburg, Albert-Einstein-Ring 8-10, 22761 Hamburg, Germany.

Funding

Center for Integrated Approaches to Undiagnosed DiseasesU01HG007690 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI LOSCALZO, JOSEPH · 2014 to 2022
$10.4M
L-2-Hydroxyglutarate and Metabolic Remodeling in HypoxiaR01HL155107 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI Joseph Loscalzo · 2021 to 2026
$4.1M
Branched-chain Keto-acids and Aerobic Glycolysis in Vascular Smooth Muscle CellsR01HL166137 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI Joseph Loscalzo · 2023 to 2026
$2.8M
Personalized protein-protein interactomes and precision medicine in pulmonary arterial hypertensionR01HL155096 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI MARON, BRADLEY · 2021 to 2024
$1.6M
NHGRI NIH HHS U01 HG007690NHLBI NIH HHS R01 HL155096NHLBI NIH HHS R01 HL155107NHLBI NIH HHS R01 HL166137
6 · The paper itself

Abstract

The need for a deeper understanding of adverse drug reaction (ADR) mechanisms is vital for improving drug safety and repurposing. This study introduces Drug Adverse Reaction Mechanism Explainer (DREAMER), a network-based framework that uses a comprehensive knowledge graph to uncover molecular mechanisms underlying ADRs and disease phenotypes. By examining shared phenotypes of drugs and diseases and their effects on protein-protein interaction networks, DREAMER identifies proteins linked to ADR mechanisms. Applied to 649 ADRs, DREAMER identified molecular mechanisms for 67 ADRs, including ventricular arrhythmia and metabolic acidosis, and emphasized pathways like GABAergic signaling and coagulation proteins in personality disorders and intracranial hemorrhage. We further demonstrate the application of DREAMER in drug repurposing and propose sotalol, ranolazine, and diltiazem as candidate drugs to be repurposed for cardiac arrest. In summary, DREAMER effectively detects molecular mechanisms underlying phenotypes, emphasizing the importance of network-based analyses with integrative data for enhancing drug safety and accelerating the discovery of novel therapeutic strategies.

Indexed as

Drug-Related Side Effects and Adverse ReactionsDrug RepositioningHumansPhenotypeProtein Interaction Mapsadverse drug reactionclinical phenotypesCP: systems biologydisease phenotypedrug repurposingdrug safetynetwork-based analysisnetwork diffusion

Identifiers

PMID39954672
PMCPMC11955268

What Socratic holds

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Registered trials

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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.