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Bhatia, H.S. ; Brunner, A.D.* ; Öztürk, F. ; Kapoor, S. ; Rong, Z. ; Mai, H. ; Thielert, M.* ; Ali, M. ; Al-Maskari, R.* ; Paetzold, J.C. ; Kofler, F. ; Todorov, M.I. ; Molbay, M. ; Kolabas, Z.I. ; Negwer, M. ; Höher, L. ; Steinke, H.* ; Dima, A.* ; Gupta, B. ; Kaltenecker, D. ; Caliskan, Ö.S. ; Brandt, D. ; Krahmer, N. ; Müller, S.* ; Lichtenthaler, S.F.* ; Hellal, F. ; Bechmann, I.* ; Menze, B.* ; Theis, F.J. ; Mann, M.* ; Ertürk, A.

Spatial proteomics in three-dimensional intact specimens.

Cell 185, 5040-5058.e19 (2022)
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Spatial molecular profiling of complex tissues is essential to investigate cellular function in physiological and pathological states. However, methods for molecular analysis of large biological specimens imaged in 3D are lacking. Here, we present DISCO-MS, a technology that combines whole-organ/whole-organism clearing and imaging, deep-learning-based image analysis, robotic tissue extraction, and ultra-high-sensitivity mass spectrometry. DISCO-MS yielded proteome data indistinguishable from uncleared samples in both rodent and human tissues. We used DISCO-MS to investigate microglia activation along axonal tracts after brain injury and characterized early- and late-stage individual amyloid-beta plaques in a mouse model of Alzheimer's disease. DISCO-bot robotic sample extraction enabled us to study the regional heterogeneity of immune cells in intact mouse bodies and aortic plaques in a complete human heart. DISCO-MS enables unbiased proteome analysis of preclinical and clinical tissues after unbiased imaging of entire specimens in 3D, identifying diagnostic and therapeutic opportunities for complex diseases. Video abstract: [Figure presented]
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Ai ; Alzheimer's ; Deep Learning ; Human Heart ; Mass Spectrometry ; Proteomics ; Robotics ; Spatial-omics ; Tbi ; Tissue Clearing; Alzheimers-disease; Mouse Model; Gene-expression; A-beta; Brain; Normalization; Resolution; Platform; Complex; Plaques
ISSN (print) / ISBN 0092-8674
e-ISSN 1097-4172
Journal Cell
Quellenangaben Volume: 185, Issue: 26, Pages: 5040-5058.e19 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute for Tissue Engineering and Regenerative Medicine (ITERM)
Helmholtz Artifical Intelligence Cooperation Unit (HAICU)
Institute of Diabetes and Cancer (IDC)
Institute of Diabetes and Obesity (IDO)
Institute of Computational Biology (ICB)
Grants Max Planck Society for the Advancement of Science
Helmholtz AI program through grant Deeproad
Nomis Heart Atlas Project Grant (Nomis Foundation)
ERC Consolidator Grant (AE)
Bundesministerium fur Bildung und Wissenschaft (BMBF)
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy
Vascular Dementia Research Foundation
International Max Planck Research School for Life Sciences (IMPRS-LS)