Cover Image

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Breinig, Marco (Author) , Lomakin, Artem (Author) , Heidari, Elyas (Author) , Ritter, Michael (Author) , Rukhovich, Gleb (Author) , Böse, Lio (Author) , Butthof, Luise (Author) , Wendler-Link, Lena (Author) , Wiethoff, Hendrik (Author) , Poth, Tanja (Author) , Sahm, Felix (Author) , Schirmacher, Peter (Author) , Stegle, Oliver (Author) , Gerstung, Moritz (Author) , Tschaharganeh, Darjus-Felix (Author)
Format: Article (Journal)
Language:English
Published: 28 July 2025
In: Nature biomedical engineering

ISSN:2157-846X
DOI:10.1038/s41551-025-01437-1
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41551-025-01437-1
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41551-025-01437-1
Get full text
Author Notes: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
Description
Summary: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.
Item Description:Gesehen am 10.12.2025
Physical Description:Online Resource
ISSN:2157-846X
DOI:10.1038/s41551-025-01437-1

Similar Items