Evidence map›Paper›PMID 39472987›Full record

ArticleJournal of translational medicine2024

Exploring potential therapeutic targets for asthma: a proteome-wide Mendelian randomization analysis.

Yuhan Jiang, Yifan Wang, Ju Guo, Zixuan Wang, Xuelin Wang, Xueming Yao, Hongxi Yang, Yingxue Zou

Abstract read
In one paragraph

Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

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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

8 authors.

Yuhan Jiang *Clinical School of Pediatrics, Tianjin Medical University, Tianjin, China.
Yifan Wang *Clinical School of Pediatrics, Tianjin Medical University, Tianjin, China.
Ju Guo *Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, 300052, China.
Zixuan WangClinical School of Pediatrics, Tianjin Medical University, Tianjin, China.
Xuelin WangDepartment of Pulmonology, Tianjin Children's Hospital (Children's Hospital of Tianjin University), Machang Compus, 225 Machang Road, Hexi District, Tianjin, 300074, China.
Xueming YaoDepartment of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, 300052, China.
Hongxi YangDepartment of Bioinformatics, School of Basic Medical Science, Tianjin Medical University, Tianjin, 300070, China. yanghongxi@tmu.edu.cn.
Yingxue ZouClinical School of Pediatrics, Tianjin Medical University, Tianjin, China. zouyingxue2015@tju.edu.cn.

Funding

Tianjin Municipal Health Commission Key Discipline Special Fund TJWJ2022XK038
6 · The paper itself

Abstract

backgroundAsthma poses a significant global health challenge, characterized by high rates of morbidity and mortality. Despite available treatments, many severe asthma patients remain poorly managed, highlighting the need for novel therapeutic strategies. This study aims to identify potential drug targets for asthma by examining the influence of circulating plasma proteins on asthma risk.

methodsThis study employs summary-data-based Mendelian randomization (MR) and two-sample MR methods to investigate the association between 2940 plasma proteins from the UK Biobank study and asthma. The analysis includes discovery (FinnGen cohort) and replication (GERA cohort) phases, with Bayesian colocalization used to validate the relationships between proteins and asthma. Furthermore, protein-protein interaction and druggability assessments were conducted on high-evidence strength protein biomarkers, and candidate drug prediction and molecular docking were performed for proteins without targeted drugs. Given the complexity of asthma pathogenesis, the study also explores the relationships between plasma proteins and asthma-related endpoints (e.g., obesity-related asthma, infection-related asthma, childhood asthma) to identify potential therapeutic targets for different subtypes.

resultsIn the discovery cohort, 75 plasma proteins were associated with asthma, including IL1RAP, IL1RL1, IL6, CXCL5, and CXCL8. Additionally, 6 proteins (IL4R, LTB, CASP8, MAX, PCDH12, and SCLY) were validated through co-localization analysis and validation cohort. The assessment of drug targetability revealed potential drug targets for IL4R, CASP8, and SCLY, while candidate drugs were predicted for LTB and MAX proteins. MAX exhibited strong binding affinity with multiple small molecules indicating a highly stable interaction and significant druggability potential. Analysis of the 75 proteins with 9 asthma-related endpoints highlighted promising targets such as DOK2, ITGAM, CA1, BTN2A1, and GZMB.

conclusionThese findings elucidate the link between asthma, its related endpoints, and plasma proteins, advancing our understanding of molecular pathogenesis and treatment strategies. The discovery of potential therapeutic targets offers new insights into asthma drug target research.

Indexed as

AsthmaMendelian Randomization AnalysisProteomeBayes TheoremBiomarkersCohort StudiesHumansMolecular Docking SimulationMolecular Targeted TherapyProtein Interaction MapsBiomarkersProteomeAsthmaDrug targetMendelian randomizationPlasma proteome

Identifiers

PMID39472987
PMCPMC11520847

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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 OpenQuestion graph.