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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: Breinig, Marco (VerfasserIn) , Lomakin, Artem (VerfasserIn) , Heidari, Elyas (VerfasserIn) , Ritter, Michael (VerfasserIn) , Rukhovich, Gleb (VerfasserIn) , Böse, Lio (VerfasserIn) , Butthof, Luise (VerfasserIn) , Wendler-Link, Lena (VerfasserIn) , Wiethoff, Hendrik (VerfasserIn) , Poth, Tanja (VerfasserIn) , Sahm, Felix (VerfasserIn) , Schirmacher, Peter (VerfasserIn) , Stegle, Oliver (VerfasserIn) , Gerstung, Moritz (VerfasserIn) , Tschaharganeh, Darjus-Felix (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 28 July 2025
In: Nature biomedical engineering

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
Volltext
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
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 10.12.2025
Beschreibung:Online Resource
ISSN:2157-846X
DOI:10.1038/s41551-025-01437-1

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