Evidence mapPaperPMID 39719581Full record

ArticleJournal of translational medicine2024

Integration of multi-omics transcriptome-wide analysis for the identification of novel therapeutic drug targets in diabetic retinopathy.

Guoguo Yi, Zhengran Li, Yuxin Sun, Xinyu Ma, Zijin Wang, Jinken Chen, Dong Cai, Ziran Zhang, Zejun Chen, Fanye Wu and 2 more

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 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.

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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

12 authors.

Guoguo Yi *Department of Ophthalmology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Zhengran Li *Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, China.
Yuxin Sun *Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, China.
Xinyu MaDepartment of Ophthalmology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, China.
Zijin WangThe Second Clinical Medicine School, Southern Medical University, Guangzhou, Guangdong, China.
Jinken ChenSchool of Architecture, South China University of Technology, Guangzhou, Guangdong, China.
Dong CaiSchool of Computer Science and Engineering, Sun Yat-Sen University, Guangzhou, China.
Ziran ZhangThe Second Clinical Medicine School, Southern Medical University, Guangzhou, Guangdong, China.
Zejun ChenThe Second Clinical Medicine School, Southern Medical University, Guangzhou, Guangdong, China.
Fanye WuThe Second Clinical Medicine School, Southern Medical University, Guangzhou, Guangdong, China.
Mingzhe CaoDepartment of Ophthalmology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518107, Guangdong Province, China.
Min FuDepartment of Ophthalmology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, China. min_fu1212@163.com.ORCID 0000-0003-2638-1756

Funding

President's Fund of Zhujiang Hospital of Southern Medical University yzjj2023ms05Scientific Research Project of Guangdong Provincial Bureau of Traditional Chinese Medicine 20241201
6 · The paper itself

Abstract

backgroundDiabetic retinopathy (DR) is the most important complication of Type 2 Diabetes (T2D) in eyes. Despite its prevalence, the early detection and management of DR continue to pose considerable challenges. Our research aims to elucidate potent drug targets that could facilitate the identification of DR and propel advancements in its therapeutic strategies.

methodsA broad multi-omics exploration of DR was presented to decipher the drug targets of DR and proliferative diabetic retinopathy (PDR). Transcriptome-Wide Association Studies (TWAS), fine-mapping and conditional analysis were applied to unearth potential tissue-specific gene associations with DR. Summary Data-based Mendelian Randomization (SMR) provided secondary analysis of high confidence genes. Cis-instrument of druggable genes were extracted from the eQTLGen Consortium and PsychENCODE, facilitating drug-target MR supported by colocalization analysis. Phenome-Wide Association Studies (PheWAS) was conducted on the high confidence genes. Metabolomic and immunomic MR-profiling further augmented our research as complement.

resultsTWAS identified multiple robust genetic loci in both DR and PDR (WFS1, RPS26, and SRPK1) through genetic associations across different tissues. Meanwhile, we have delineated both the commonalities and discrepancies between DR and PDR at the transcriptomic level, represented by DCLRE1B as the hub gene that DR progressed into PDR. SMR revealed 92 key DR-related genes and 55 PDR-related genes. HLA-DQ family genes have a frequent occurrence, while RPS26, WFS1 and SRPK1 were validated as the genetic network's linchpins. Drug-target MR casted ERBB3 and SRPK1 as candidate effector genes for DR and PDR susceptibility. In addition, metabolomics and immunomics analyses also revealed multifaceted pathogenic factors for DR.

conclusionsOur research offers targeted therapeutic insights for early-stage DR and facilitates multi-omic comparisons of it and PDR.

Indexed as

Diabetic RetinopathyGene Expression ProfilingGenome-Wide Association StudyTranscriptomeHumansMendelian Randomization AnalysisMetabolomicsMolecular Targeted TherapyMultiomicsPhenotypeQuantitative Trait LociDiabetic retinopathy (DR)Drug-target MRImmunomicsMendelian randomization (MR)MetabolomicsMulti-omicsSummary data-based Mendelian randomisation (SMR)Transcriptome-wide association studies (TWAS)

Identifiers

PMID39719581
PMCPMC11667901

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.