Evidence map›Paper›PMID 40721510›Full record

ArticleNature biomedical engineering2026

Integrated in vivo combinatorial functional genomics and spatial transcriptomics of tumours to decode genotype-to-phenotype relationships.

Marco Breinig, Artem Lomakin, Elyas Heidari, Michael Ritter, Gleb Rukhovich, Lio Böse, Luise Butthof, Lena Wendler-Link, Hendrik Wiethoff, Tanja Poth and 5 more

Abstract read
In one paragraph

Article in Nature biomedical engineering, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Marco Breinig *Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. marco.breinig@gmail.com.ORCID http://orcid.org/0009-0000-9740-2986
Artem Lomakin *Artificial Intelligence in Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Elyas Heidari *Artificial Intelligence in Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Michael RitterDepartment of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.
Gleb RukhovichArtificial Intelligence in Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Lio BöseInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Luise ButthofInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Lena Wendler-LinkInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Hendrik WiethoffInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-8450-653X
Tanja PothCenter for Model System and Comparative Pathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Felix SahmDepartment of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-5441-1962
Peter SchirmacherInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Oliver StegleComputational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Moritz GerstungArtificial Intelligence in Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. moritz.gerstung@dkfz.de.ORCID http://orcid.org/0000-0001-6709-963X
Darjus F TschaharganehInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. d.tschaharganeh@dkfz.de.

Funding

Deutsche Forschungsgemeinschaft (German Research Foundation) TS 293/3-1
6 · The paper itself

Abstract

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.

Indexed as

Gene Expression ProfilingGenomicsLiver NeoplasmsNeoplasmsTranscriptomeAnimalsGene Expression Regulation, NeoplasticGenotypeHumansMicePhenotype

Identifiers

PMID40721510
PMCPMC12823398

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.