Project 1: Predictive Modeling for Biomarker Identification and In-Silico Therapy Design in Pediatric Diffuse Midline Glioma
Background:
Recent advances in pediatric neuro-oncology have made new therapies, such as the DRD2 antagonist Modeyso (ONC201), available for children with DMG. However, individual responses vary substantially, and there is a need for computational tools to predict treatment outcomes and identify biomarkers of resistance and sensitivity.
Project Description:
This PhD project will develop and validate AI-based prediction models that link molecular tumor profiles to drug response, integrating multi-omics data (transcriptomics, methylation, CNV, mutational data) and preclinical screening results. The goal is to establish a clinically relevant framework for predicting treatment response and for in-silico identification of combination therapies in pediatric DMG. This project is suggested to compare two possible tracks to assess model generalization: foundation models and mechanistic learning to guide the selection of training regimes, included features and architecture design based on the current understanding of the drug's mechanism of action.
Methods and Data:
- Multi-omics data integration from pediatric and pan-cancer datasets including public and private data provided by our collaborators
- Deep learning and explainable AI approaches for drug response prediction
- Benchmarking of foundation models vs. meachnistic learning approaches for drug response modelling
- Model interpretation to identify molecular determinants of treatment sensitivity and resistance to recommend combination therapies
Candidate Profile:
- MSc in computer science, data science, bioinformatics, or a related field
- Experience in computational biology and the processing of different types of omics data
- Interest in translational applications of AI in pediatric oncology
Project 2: Personalized Radiotherapy for Pediatric Diffuse Midline Glioma
Background:
Radiotherapy remains the cornerstone of palliation and improved overall survival for DMG, yet its effect varies widely across patients. Predicting individual response before treatment and optimizing therapy delivery could improve both survival and quality of life.
Project Description:
This project aims to develop and test computational models that predict individual RT response based on pre-treatment imaging data and explore personalized adaptations of fractionation and dose distribution. Combining mechanistic modeling with AI-based image analysis, the project will contribute to a framework for individualized RT planning in pediatric brain tumors. Key challenges, such as limited data imply a dedicated training scheme and exploration of relevant transfer learning scenarios from adult GBM data available both publicly and at Inselspital.
Methods and Data:
- MRI-based prediction of RT response using MRI foundation models
- Mechanistic learning frameworks for tumor growth and radiosensitivity modeling
- Counterfactual simulations of alternative fractionation schemes
- Generative space-time modeling for anatomical prediction of tumor recurrence for a given radiotherapy treatment plan
Candidate Profile:
- MSc in (medical) physics, biomedical engineering, computer vision, or a related discipline
- Experience with medical image analysis and/or generative modeling
- Interest in radiotherapy modeling and quantitative imaging
