Bidirectional linkage of DNA barcodes for the multiplexed mapping of higher-order protein interactions in cells.

Autor: Liu Y; Institute for Health Innovation and Technology, National University of Singapore, Singapore, Singapore.; Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, Singapore., Sundah NR; Institute for Health Innovation and Technology, National University of Singapore, Singapore, Singapore.; Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, Singapore., Ho NRY; Institute for Health Innovation and Technology, National University of Singapore, Singapore, Singapore., Shen WX; Department of Pharmacy and Pharmaceutical Sciences, Faculty of Science, National University of Singapore, Singapore, Singapore., Xu Y; Institute for Health Innovation and Technology, National University of Singapore, Singapore, Singapore.; Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, Singapore., Natalia A; Institute for Health Innovation and Technology, National University of Singapore, Singapore, Singapore.; Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, Singapore., Yu Z; Institute for Health Innovation and Technology, National University of Singapore, Singapore, Singapore.; Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, Singapore., Seet JE; Department of Pathology, National University Hospital, Singapore, Singapore., Chan CW; Department of Surgery, National University Hospital, Singapore, Singapore.; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Loh TP; Institute for Health Innovation and Technology, National University of Singapore, Singapore, Singapore.; Department of Laboratory Medicine, National University Hospital, Singapore, Singapore., Lim BY; Institute for Health Innovation and Technology, National University of Singapore, Singapore, Singapore. brianlim@comp.nus.edu.sg.; Department of Computer Science, School of Computing, National University of Singapore, Singapore, Singapore. brianlim@comp.nus.edu.sg., Shao H; Institute for Health Innovation and Technology, National University of Singapore, Singapore, Singapore. huilin.shao@nus.edu.sg.; Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, Singapore. huilin.shao@nus.edu.sg.; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. huilin.shao@nus.edu.sg.; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore. huilin.shao@nus.edu.sg.
Jazyk: angličtina
Zdroj: Nature biomedical engineering [Nat Biomed Eng] 2024 Jul; Vol. 8 (7), pp. 909-923. Date of Electronic Publication: 2024 Jun 19.
DOI: 10.1038/s41551-024-01225-3
Abstrakt: Capturing the full complexity of the diverse hierarchical interactions in the protein interactome is challenging. Here we report a DNA-barcoding method for the multiplexed mapping of pairwise and higher-order protein interactions and their dynamics within cells. The method leverages antibodies conjugated with barcoded DNA strands that can bidirectionally hybridize and covalently link to linearize closely spaced interactions within individual 3D protein complexes, encoding and decoding the protein constituents and the interactions among them. By mapping protein interactions in cancer cells and normal cells, we found that tumour cells exhibit a larger diversity and abundance of protein complexes with higher-order interactions. In biopsies of human breast-cancer tissue, the method accurately identified the cancer subtype and revealed that higher-order protein interactions are associated with cancer aggressiveness.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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