Integrated in vivo combinatorial functional genomics and spatial transcriptomics of tumours to decode genotype-to-phenotype relationships
Advancing spatially resolved in vivo functional genomes will link complex genetic alterations prevalent in cancer to critical disease phenotypes within tumour ecosystems. To this end, we developed PERTURB-CAST, a method to streamline the identification of perturbations at the tissue level. By adapti...
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| Hauptverfasser: | , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
28 July 2025
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| In: |
Nature biomedical engineering
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| ISSN: | 2157-846X |
| DOI: | 10.1038/s41551-025-01437-1 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41551-025-01437-1 Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41551-025-01437-1 
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| Verfasserangaben: | Marco Breinig, Artem Lomakin, Elyas Heidari, Michael Ritter, Gleb Rukhovich, Lio Böse, Luise Butthof, Lena Wendler-Link, Hendrik Wiethoff, Tanja Poth, Felix Sahm, Peter Schirmacher, Oliver Stegle, Moritz Gerstung, and Darjus F. Tschaharganeh |
MARC
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| 520 | |a Advancing spatially resolved in vivo functional genomes will link complex genetic alterations prevalent in cancer to critical disease phenotypes within tumour ecosystems. To this end, we developed PERTURB-CAST, a method to streamline the identification of perturbations at the tissue level. By adapting RNA-templated ligation probes, PERTURB-CAST leverages commercial 10X Visium spatial transcriptomics to integrate perturbation mapping with transcriptome-wide phenotyping in the same tissue section using a widely available single-readout platform. In addition, we present CHOCOLAT-G2P, a scalable framework designed to study higher-order combinatorial perturbations that mimic tumour heterogeneity. We apply it to investigate tissue-level phenotypic effects of combinatorial perturbations that induce autochthonous mosaic liver tumours. | ||
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