Which genes and signaling pathways does a cancer cell require to survive? And which of these could serve as therapeutic targets? The pan-European initiative PRECISE (Predictive Relationships Explaining Cancer Genetic Interactions and Synthetic Essentiality) aims to identify such vulnerabilities not only through labor-intensive laboratory experiments but also by predicting them using computational models. The University Hospital Bonn (UKB) and the University of Bonn, represented by Prof. Dr. Maximilian Billmann and Prof. Dr. Jonathan Schmid-Burgk, are among the founding partners of the consortium. The scientific vision of the initiative has now been published in a commentary in Nature Genetics.
Over the past several years, large-scale genetic screens have revealed numerous dependencies of cancer cells. The resulting dependency maps show, for example, which genes or molecular signaling pathways specific tumor cells rely on. However, these maps have so far been largely descriptive: they provide only limited insight into why a particular vulnerability arises, the biological context in which it occurs, and how it changes under the selective pressure of therapy. In addition, current findings can only be transferred to previously unstudied tumors and biological settings to a limited extent.
A central component of PRECISE is the investigation of genetic interactions. One example is synthetic lethality, where two genetic alterations or perturbations are each tolerated individually by a cell but become lethal when combined. Such interactions may reveal promising opportunities for targeted therapies. Beyond cell survival, PRECISE also investigates changes in cellular states, cellular programs, and adaptive responses using a range of molecular and imaging-based technologies.
The PRECISE consortium brings together more than 30 experimental and computational research groups from over 20 research institutes and universities across nine European countries. The partners combine data from patient cohorts and disease-relevant model systems, including cell lines and organoids, with targeted genetic perturbations using technologies such as CRISPR, multimodal molecular profiling, imaging, machine learning, and artificial intelligence. The goal is to derive general principles that enable the prediction of cancer cell vulnerabilities even in biological contexts that have not yet been experimentally investigated.
A defining feature of PRECISE is its continuous predict-test-learn cycle. Computational models not only analyze existing data but also prioritize the genetic perturbations and experiments expected to yield the greatest scientific insight. These predictions are then tested experimentally in the laboratory. The resulting data are fed back into the models, enabling their predictive performance to improve iteratively over time. This closed-loop approach is designed to make experimental planning more efficient and accelerate the discovery of therapeutically relevant cancer vulnerabilities.
In the long term, this strategy is expected to expand the scope of precision oncology, particularly for patients whose tumors currently lack clinically actionable targets based on existing molecular diagnostics. The models are also intended to help anticipate potential mechanisms of therapy resistance, identify rational combination therapies, and determine the biological contexts in which a given vulnerability is most likely to be therapeutically relevant.
Prof. Dr. Maximilian Billmann of the Institute of Human Genetics at UKB is a member of the University of Bonn's Transdisciplinary Research Areas (TRAs) "Modelling" and "Life and Health." "Europe is home to many of the leading scientists in our field. PRECISE now provides a framework that will allow us to address the challenges of precision oncology much more effectively together in the future," says Billmann. As senior author, he recently published a genome-wide map of genetic interactions in a human cell model in the journal Cell.
"In PRECISE, we are now trying to learn general principles from our own and other similar datasets - many of which were also generated by PRECISE members - to make predictions that can address concrete challenges in oncology," Billmann explains.
Prof. Dr. Jonathan Schmid-Burgk of the Institute of Clinical Chemistry and Clinical Pharmacology at UKB is also a founding member of the consortium. He conducts research within the ImmunoSensation³ Cluster of Excellence and the University of Bonn's "Life and Health" TRA and has been recognized multiple times as a Clarivate Highly Cited Researcher.
His laboratory contributes NIS-Seq, a novel light microscopy-based screening technology that was recently published in Nature Biotechnology. The method links microscopically observable characteristics of individual cells with targeted genetic perturbations. Within PRECISE, it will help systematically elucidate gene functions in tumor cells.
"Together with other laboratories in the PRECISE consortium, we want to study complex functions of protein-coding genes in tumor cells - not only genes that are absolutely essential for cell survival, but also those that program cellular behavior. Working closely with our clinical and tumor biology partners in the consortium, we aim to identify therapeutic targets that can be exploited to attack tumor cells while being less important in healthy cells," Schmid-Burgk explains, describing his role within the European collaboration.
PRECISE is coordinated by Francesco Iorio of Human Technopole in Milan and Mathew J. Garnett of the Wellcome Sanger Institute in the United Kingdom. The consortium is committed to shared experimental standards, harmonized analytical workflows, and the FAIR principles, ensuring that data and scientific tools are Findable, Accessible, Interoperable, and Reusable.
Further information about the consortium and its objectives is available on the PRECISE web portal: https://precise-eu.org/
Publication
Francesco Iorio et al. PRECISE as a European initiative for cancer-vulnerability mapping and prediction. Nature Genetics. DOI: 10.1038/s41588-026-02658-z
https://www.nature.com/articles/s41588-026-02658-z
Scientific Contacts
Prof. Dr. Jonathan Schmid-Burgk
Institute of Clinical Chemistry and Clinical Pharmacology
University Hospital Bonn
ImmunoSensation³ Cluster of Excellence and Transdisciplinary Research Area "Life & Health", University of Bonn
E-mail: jsb@uni-bonn.de
Jun.-Prof. Dr. Maximilian Billmann
Institute of Human Genetics
University Hospital Bonn
Transdisciplinary Research Areas "Modelling" & "Life and Health", University of Bonn
E-mail: m.billmann@uni-bonn.de
Press contact
Dr. Inka Väth
Deputy Press Officer, University Hospital Bonn (UKB)
Communications and Media Office, University Hospital Bonn (UKB)
Phone: +49 228 287-10596
E-mail: inka.vaeth@ukbonn.de
