Evidence map›Paper›PMID 37863056›Full record

ArticleCell2023

Liquid-biopsy proteomics combined with AI identifies cellular drivers of eye aging and disease in vivo.

Julian Wolf, Ditte K Rasmussen, Young Joo Sun, Jennifer T Vu, Elena Wang, Camilo Espinosa, Fabio Bigini, Robert T Chang, Artis A Montague, Peter H Tang and 5 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 3 pooled it
21.1field-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

86 citing papers in PubMed, 3 syntheses or guidelines pooled it, 93 citations in OpenAlex.

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26 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

15 authors at 6 institutions in 3 countries.

Julian WolfMolecular Surgery Laboratory, Stanford University, Palo Alto, CA 94304, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304, USA.
Ditte K RasmussenMolecular Surgery Laboratory, Stanford University, Palo Alto, CA 94304, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304, USA; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
Young Joo SunMolecular Surgery Laboratory, Stanford University, Palo Alto, CA 94304, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304, USA.
Jennifer T VuMolecular Surgery Laboratory, Stanford University, Palo Alto, CA 94304, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304, USA.
Elena WangMolecular Surgery Laboratory, Stanford University, Palo Alto, CA 94304, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304, USA.
Camilo EspinosaDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA 94305, USA.
Fabio BiginiMolecular Surgery Laboratory, Stanford University, Palo Alto, CA 94304, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304, USA.
Robert T ChangDepartment of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304, USA.
Artis A MontagueDepartment of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304, USA.
Peter H TangDepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA; Retina Consultants of Minnesota, Edina, MN 55435, USA.
Prithvi MruthyunjayaDepartment of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304, USA.
Nima AghaeepourDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA 94305, USA.
Antoine DufourDepartments of Physiology and Pharmacology & Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Alexander G BassukDepartments of Pediatrics and Neurology, The Iowa Neuroscience Institute (INI), University of Iowa, Iowa City, IA 52242, USA.
Vinit B MahajanMolecular Surgery Laboratory, Stanford University, Palo Alto, CA 94304, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA. Electronic address: vinit.mahajan@stanford.edu.
Palo Alto University · USSmith-Kettlewell Eye Research Institute · USStanford Medicine · USUniversity of Calgary · CAUniversity of Iowa · USUniversity of Minnesota · US

Funding

University of Iowa Hawkeye Intellectual and Developmental Disabilities Research Center (Hawk-IDDRC)P50HD103556 · NICHD · UNIVERSITY OF IOWA · PI EDWIN TED G. ABEL, Lane Strathearn · 2021 to 2026
$8.5M
Stanford Vision Research CoreP30EY026877 · NEI · STANFORD UNIVERSITY · PI Jeffrey L Goldberg · 2017 to 2026
$8.0M
Improving rigor and reproducibility in adaptive optics ophthalmoscopyR01EY031360 · NEI · STANFORD UNIVERSITY · PI DUBRA, ALFREDO · 2020 to 2023
$2.3M
Machine Learning for Integrative Modeling of the Immune System in Clinical SettingsR35GM138353 · NIGMS · STANFORD UNIVERSITY · PI AGHAEEPOUR, NIMA · 2020 to 2024
$2.2M
Inflammatory Gene Transcription in the RetinaR01EY030151 · NEI · STANFORD UNIVERSITY · PI BASSUK, ALEXANDER G, MAHAJAN, VINIT B · 2020 to 2024
$2.0M
Proteomic Biomarkers of Intraocular InfectionR01EY031952 · NEI · STANFORD UNIVERSITY · PI BASSUK, ALEXANDER G, FERGUSON, POLLY J · 2020 to 2023
$1.6M
NEI NIH HHS P30 EY026877NEI NIH HHS R01 EY030151NEI NIH HHS R01 EY031360NEI NIH HHS R01 EY031952NICHD NIH HHS P50 HD103556NIGMS NIH HHS R35 GM138353
6 · The paper itself

Abstract

Single-cell analysis in living humans is essential for understanding disease mechanisms, but it is impractical in non-regenerative organs, such as the eye and brain, because tissue biopsies would cause serious damage. We resolve this problem by integrating proteomics of liquid biopsies with single-cell transcriptomics from all known ocular cell types to trace the cellular origin of 5,953 proteins detected in the aqueous humor. We identified hundreds of cell-specific protein markers, including for individual retinal cell types. Surprisingly, our results reveal that retinal degeneration occurs in Parkinson's disease, and the cells driving diabetic retinopathy switch with disease stage. Finally, we developed artificial intelligence (AI) models to assess individual cellular aging and found that many eye diseases not associated with chronological age undergo accelerated molecular aging of disease-specific cell types. Our approach, which can be applied to other organ systems, has the potential to transform molecular diagnostics and prognostics while uncovering new cellular disease and aging mechanisms.

Indexed as

AgingAqueous HumorArtificial IntelligenceLiquid BiopsyProteomicsBiopsyHumansParkinson Diseaseagingartificial intelligencediabetic retinopathyliquid biopsylongevityParkinson’s diseaseproteomicsretinitis pigmentosasingle-cell analysisuveitis

Identifiers

PMID37863056
PMCPMC10720485
OpenAlexW4387783953

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.