Evidence map›Paper›PMID 42400003›Full record

ArticleGenome medicine2026

Multi-modal data integration reveals functionally credible predictive biomarkers in ovarian cancer.

Taru A Muranen, Andreas Hainari, Daria Afenteva, Wojciech Senkowski, Jaana Oikkonen, Johann Dreo, Kyriaki Driva, Susanna Holmström, Veli-Matti Isoviita, Alexandra Lahtinen and 20 more

Abstract read
In one paragraph

Article in Genome medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

30 authors.

Taru A MuranenResearch Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Andreas HainariResearch Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Daria AfentevaResearch Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Wojciech SenkowskiBiotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
Jaana OikkonenResearch Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Johann DreoComputational Systems Biomedicine Lab, Institut Pasteur, Universite Paris Cité, Paris, France.
Kyriaki DrivaBiotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
Susanna HolmströmResearch Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Veli-Matti IsoviitaResearch Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Alexandra LahtinenResearch Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Kari LavikkaResearch Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Yilin LiResearch Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Marta LovinoDepartment of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Ilari MaaralaResearch Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Giovanni MarchiResearch Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Francesca MiccolisDepartment of Engineering, Enzo Ferrari, University of Modena and Reggio Emilia, Modena, Italy.
Giulia MicoliResearch Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Matthieu NajmComputational Systems Biomedicine Lab, Institut Pasteur, Universite Paris Cité, Paris, France.
Ann-Christin OstwaldtResearch Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Pablo Rodriguez-MierFaculty of Medicine and Heidelberg University Hospital, Institute for Computational Biomedicine, Heidelberg University, Heidelberg, Germany.
Jenni SöderlundDepartment of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland.
Sakari HietanenDepartment of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland.
Anni VirtanenDepartment of Pathology, University of Helsinki and HUS Diagnostic Center, Helsinki, Finland.
Julio Saez-RodriguezFaculty of Medicine and Heidelberg University Hospital, Institute for Computational Biomedicine, Heidelberg University, Heidelberg, Germany.
Elisa FicarraDepartment of Engineering, Enzo Ferrari, University of Modena and Reggio Emilia, Modena, Italy.
Benno SchwikowskiComputational Systems Biomedicine Lab, Institut Pasteur, Universite Paris Cité, Paris, France.
Erika AlanneDepartment of Oncology, Turku University Hospital and Western Finland Cancer Center, Turku, Finland.
Krister WennerbergBiotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
Sampsa HautaniemiResearch Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland. sampsa.hautaniemi@helsinki.fi.
Johanna HynninenDepartment of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland. mijohy@utu.fi.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPrecision oncology aims to tailor treatment according to tumor-specific molecular alterations, but the success of aberration-guided therapies has been limited in clinical trials. Here, we develop an integrated whole-genome and transcriptome workflow to systematically distinguish functionally credible, predictive driver aberrations from non-functional alterations across all classes of genomic events.

methodsWe applied the integrated omics workflow to 335 patients with ovarian high-grade serous carcinoma (HGSC) enrolled in the observational DECIDER study. Tumor samples were collected from multiple cancer sites as part of the standard cancer care. DNA and RNA were extracted together from snap-frozen tumor samples and sent to whole-genome and transcriptome sequencing. Sequencing data were processed with the Anduril 2 pipeline for detection and validation of short somatic changes and with the HMW toolkit and the nf-core/rnafusion pipeline for assessment of structural changes. Aberration-specific drug sensitivity was tested in patient-derived organoids with a drug screen combining targeted agents and chemotherapy.

resultsUsing an agnostic integrated omics analysis, we identified clinically relevant ESCAT Tier II-III alterations in more than 40% of the patients, even though 58% of all nominally pathogenic variants proved to be false positives. Credible aberrations were predominantly clonal, detected across anatomical sites, and preserved from diagnosis to relapse, indicating early establishment during tumor evolution. The most recurrent actionable event was NF1 deficiency, which was associated with a robust transcriptional footprint and marked sensitivity to KRAS- and MEK-inhibition in patient-derived organoids. Notably, integrated DNA-RNA analysis enabled discrimination of treatment-guiding aberrations from false-positive findings that would otherwise misinform treatment selection and confound clinical trial outcomes.

conclusionsOur findings provide a strategy for more reliable biomarker detection in precision oncology, inform biomarker-guided clinical trial design, and reveal unexploited therapeutic vulnerabilities in HGSC.

Indexed as

Biomarkers, TumorOvarian NeoplasmsFemaleGene Expression ProfilingGenomicsHumansMultiomicsMutationTranscriptomeBiomarkers, TumorBiomarkerHigh-grade serous carcinomaMulti-omicsMutationOvarian cancerPrecision oncologyTargeted therapy

Identifiers

PMID42400003
PMCPMC13579925

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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.