Evidence map›Paper›PMID 42423409›Full record

ArticleInvestigative ophthalmology & visual science2026

Deep Proteomic Analysis With Machine Learning Identifies Aqueous Humor Biomarkers of ADAMTSL4-associated Congenital Ectopia Lentis.

Xinyao Chen, Xin Shen, Wannan Jia, Yalei Wang, Qiuyi Huo, Yanbo Xiao, Yulin Zhang, Linzhao Li, Xuqing Gao, Guangqi A and 8 more

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In one paragraph

Article in Investigative ophthalmology & visual science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

18 authors.

Xinyao ChenEye Institute and Department of Ophthalmology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.
Xin ShenEye Institute and Department of Ophthalmology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.
Wannan JiaEye Institute and Department of Ophthalmology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.
Yalei WangEye Institute and Department of Ophthalmology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.
Qiuyi HuoEye Institute and Department of Ophthalmology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.
Yanbo XiaoEye Institute and Department of Ophthalmology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.
Yulin ZhangEye Institute and Department of Ophthalmology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.
Linzhao LiEye Institute and Department of Ophthalmology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.
Xuqing GaoState Key Laboratory of Genetic Engineering, National Center for Experimental Biology Education, School of Life Sciences, Fudan University, Shanghai, China.
Guangqi AState Key Laboratory of Genetic Engineering, National Center for Experimental Biology Education, School of Life Sciences, Fudan University, Shanghai, China.
Fengjing YangState Key Laboratory of Genetic Engineering, National Center for Experimental Biology Education, School of Life Sciences, Fudan University, Shanghai, China.
Yilin ChenState Key Laboratory of Genetic Engineering, National Center for Experimental Biology Education, School of Life Sciences, Fudan University, Shanghai, China.
Tianhui ChenEye Institute and Department of Ophthalmology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.
Min ZhangEye Institute and Department of Ophthalmology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.
Jin YangEye Institute and Department of Ophthalmology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.
Yan PiState Key Laboratory of Genetic Engineering, National Center for Experimental Biology Education, School of Life Sciences, Fudan University, Shanghai, China.
Zexu ChenEye Institute and Department of Ophthalmology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.
Yongxiang JiangEye Institute and Department of Ophthalmology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: To systematically characterize aqueous humor (AH) proteomic alterations in ADAMTSL4-associated congenital ectopia lentis (CEL) and to identify disease-related molecular features. Methods: Mass spectrometry-based deep data-independent acquisition (deep DIA) proteomics was employed to profile AH proteomes from pediatric ADAMTSL4-associated CEL patients. Differentially expressed proteins (DEPs) were analyzed using functional enrichment and gene set enrichment analysis. Weighted gene co-expression network analysis (WGCNA) identified disease-related protein modules. Candidate biomarkers were prioritized using machine learning, followed by technical confirmation using intelligent parallel reaction monitoring (iPRM) and clinical correlation analysis. Transcriptional changes of selected candidates were assessed by quantitative PCR in ADAMTSL4-knockdown human retinal pigment epithelial cells, human fibroblasts, and adamtsl4-knockout zebrafish. Results: Deep DIA quantified 1865 AH proteins, among which 265 DEPs were identified and enriched in extracellular matrix (ECM) remodeling, complement-coagulation cascades, and lipid transport pathways. Expression-based stratification revealed tier-specific functional patterns. WGCNA identified modules significantly associated with ocular phenotypes. Machine learning prioritized six candidate biomarkers (ADAMTS3, APOC2, AMBP, KLKB1, SDC4, and ENPP2), of which APOC2, AMBP, KLKB1, and ENPP2 achieved targeted confirmation by iPRM; APOC2, KLKB1, and ENPP2 were correlated with axial length or choroidal thickness. In ADAMTSL4-knockdown cells, ENPP2, MYDGF, and CA2 were downregulated and LCAT was upregulated, consistent with proteomic findings. MYDGF further showed a concordant directional change in the zebrafish model. Conclusions: This study established a high-resolution AH proteomic profile of ADAMTSL4-associated CEL, revealing coordinated molecular alterations in ECM disruption, complement-coagulation activation, and dysregulated lipid homeostasis, providing integrated molecular insights and candidate molecular features for understanding this rare ocular disorder.

Indexed as

ADAMTS ProteinsAqueous HumorBiomarkersEctopia LentisMachine LearningProteomeProteomicsAnimalsFemaleHumansMass SpectrometryRetinal Pigment EpitheliumZebrafishADAMTSL4 protein, humanADAMTS ProteinsBiomarkersProteome

Identifiers

PMID42423409
PMCPMC13367205

What Socratic holds

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LicenceCC BY-NC-ND
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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.