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Proteomics

DISCO-MS combines spatial proteomics with whole-organ imaging

Nature Biotechnology volume 41, page 194 (2023)Cite this article

Recent years have seen rapid advances in spatial technologies, both for sequencing-based methods and for spatially resolved mass spectrometry. However, both types of method deliver two-dimensional information, and the third dimension can be added by analyzing adjacent slices of a tissue with downstream computational alignment and integration. Writing in Cell, Bhatia et al. combine whole-organ or whole-specimen clearing and imaging techniques with robotic sample extraction, deep-learning-based image analysis, and high-sensitivity mass spectrometry optimized for small sample sizes.

The authors identified clearing protocols compatible with mass spectrometry-based proteome analysis and demonstrated that robotic sample extraction could be performed for regions of interest identified by fluorescent labeling and computational image analysis. Applied to brain samples of an Alzheimer’s disease mouse model, a U-net-based deep learning architecture identified amyloid-β plaques and a proteomic comparison of regions with and without plaques and between samples from young and old mice identified differentially enriched proteins, including known disease-related proteins as well as new candidates. Another application investigated the proteome of early plaque formation along the coronary artery of the human heart.

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  1. Nature Biotechnology https://www.nature.com/nbt

    Anne Doerr

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  1. Anne Doerr
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Doerr, A. DISCO-MS combines spatial proteomics with whole-organ imaging. Nat Biotechnol 41, 194 (2023). https://doi.org/10.1038/s41587-023-01699-7

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