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

Publication ,  Journal Article
Wolf, J; Rasmussen, DK; Sun, YJ; Vu, JT; Wang, E; Espinosa, C; Bigini, F; Chang, RT; Montague, AA; Tang, PH; Mruthyunjaya, P; Aghaeepour, N ...
Published in: Cell
October 26, 2023

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.

Duke Scholars

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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

October 26, 2023

Volume

186

Issue

22

Start / End Page

4868 / 4884.e12

Location

United States

Related Subject Headings

  • Proteomics
  • Parkinson Disease
  • Liquid Biopsy
  • Humans
  • Developmental Biology
  • Biopsy
  • Artificial Intelligence
  • Aqueous Humor
  • Aging
  • 32 Biomedical and clinical sciences
 

Citation

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Wolf, J., Rasmussen, D. K., Sun, Y. J., Vu, J. T., Wang, E., Espinosa, C., … Mahajan, V. B. (2023). Liquid-biopsy proteomics combined with AI identifies cellular drivers of eye aging and disease in vivo. Cell, 186(22), 4868-4884.e12. https://doi.org/10.1016/j.cell.2023.09.012
Wolf, Julian, Ditte K. Rasmussen, Young Joo Sun, Jennifer T. Vu, Elena Wang, Camilo Espinosa, Fabio Bigini, et al. “Liquid-biopsy proteomics combined with AI identifies cellular drivers of eye aging and disease in vivo.Cell 186, no. 22 (October 26, 2023): 4868-4884.e12. https://doi.org/10.1016/j.cell.2023.09.012.
Wolf J, Rasmussen DK, Sun YJ, Vu JT, Wang E, Espinosa C, et al. Liquid-biopsy proteomics combined with AI identifies cellular drivers of eye aging and disease in vivo. Cell. 2023 Oct 26;186(22):4868-4884.e12.
Wolf, Julian, et al. “Liquid-biopsy proteomics combined with AI identifies cellular drivers of eye aging and disease in vivo.Cell, vol. 186, no. 22, Oct. 2023, pp. 4868-4884.e12. Pubmed, doi:10.1016/j.cell.2023.09.012.
Wolf J, Rasmussen DK, Sun YJ, Vu JT, Wang E, Espinosa C, Bigini F, Chang RT, Montague AA, Tang PH, Mruthyunjaya P, Aghaeepour N, Dufour A, Bassuk AG, Mahajan VB. Liquid-biopsy proteomics combined with AI identifies cellular drivers of eye aging and disease in vivo. Cell. 2023 Oct 26;186(22):4868-4884.e12.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

October 26, 2023

Volume

186

Issue

22

Start / End Page

4868 / 4884.e12

Location

United States

Related Subject Headings

  • Proteomics
  • Parkinson Disease
  • Liquid Biopsy
  • Humans
  • Developmental Biology
  • Biopsy
  • Artificial Intelligence
  • Aqueous Humor
  • Aging
  • 32 Biomedical and clinical sciences