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Liquid-biopsy proteomics combined with AI identifies cellular drivers of eye aging and disease in vivo.
Wolf, Julian; Rasmussen, Ditte K; Sun, Young Joo; Vu, Jennifer T; Wang, Elena; Espinosa, Camilo; Bigini, Fabio; Chang, Robert T; Montague, Artis A; Tang, Peter H; Mruthyunjaya, Prithvi; Aghaeepour, Nima; Dufour, Antoine; Bassuk, Alexander G; Mahajan, Vinit B.
Affiliation
  • Wolf J; Molecular Surgery Laboratory, Stanford University, Palo Alto, CA 94304, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304, USA.
  • Rasmussen DK; Molecular 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.
  • Sun YJ; Molecular Surgery Laboratory, Stanford University, Palo Alto, CA 94304, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304, USA.
  • Vu JT; Molecular Surgery Laboratory, Stanford University, Palo Alto, CA 94304, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304, USA.
  • Wang E; Molecular Surgery Laboratory, Stanford University, Palo Alto, CA 94304, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304, USA.
  • Espinosa C; Department 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, St
  • Bigini F; Molecular Surgery Laboratory, Stanford University, Palo Alto, CA 94304, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304, USA.
  • Chang RT; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304, USA.
  • Montague AA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304, USA.
  • Tang PH; Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA; Retina Consultants of Minnesota, Edina, MN 55435, USA.
  • Mruthyunjaya P; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304, USA.
  • Aghaeepour N; Department 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, St
  • Dufour A; Departments of Physiology and Pharmacology & Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
  • Bassuk AG; Departments of Pediatrics and Neurology, The Iowa Neuroscience Institute (INI), University of Iowa, Iowa City, IA 52242, USA.
  • Mahajan VB; Molecular 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.
Cell ; 186(22): 4868-4884.e12, 2023 10 26.
Article in En | MEDLINE | ID: mdl-37863056
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Aqueous Humor / Aging / Artificial Intelligence / Proteomics / Liquid Biopsy Limits: Humans Language: En Journal: Cell Year: 2023 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Aqueous Humor / Aging / Artificial Intelligence / Proteomics / Liquid Biopsy Limits: Humans Language: En Journal: Cell Year: 2023 Type: Article Affiliation country: United States