INTEGRATE | Integrated Mechanistic Modelling and Analysis of Large-scale Biomedical Data

Summary
Modern cancer therapeutics target signalling processes within the cancer cells and the interaction of cancer and immune cells. A comprehensive understanding of these signalling processes is therefore essential to identify drug targets, plan clinical trials, and to select suitable drugs, drug combinations and drug dosages for a specific patient. Yet, most of the available mathematical models capture only a small number of molecular species and pathways, thereby ignoring important crosstalk and feedback loops. Furthermore, these models are usually based on experimental data for cell lines, which behave differently from complex cancer tissues.

In INTEGRATE, I will develop computational methods for the full process of data-driven modelling of signalling processes in cancer, ranging from model development to parameterisation all the way to uncertainty analysis. To this end, I will combine methods from the fields of mathematical modelling, machine learning, and signal processing with established approaches in systems biology. The model development will employ natural language processing and an automatic testing framework. For federated model inference, I will develop scalable mini-batch optimisation and marginalisation based uncertainty quantification. To refine models, I will exploit tools from signal processing, such as blind identification of latent variables. I will apply the developed scalable mechanistic modelling approach to integrate large-scale biomedical data for molecular phenotyping studies and clinical trials across sites. This will provide mechanistic models reconciling the available data.

The study will, for the first time, combine mechanistic modelling and machine learning for the integrated analysis of patient-derived omics and phenotypic data. By linking these data sources, INTEGRATE will deepen our understanding of biological signal processing and provide the basis for the development of digital twins.
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Web resources: https://cordis.europa.eu/project/id/101126146
Start date: 01-05-2024
End date: 30-04-2029
Total budget - Public funding: 1 854 546,00 Euro - 1 854 546,00 Euro
Cordis data

Original description

Modern cancer therapeutics target signalling processes within the cancer cells and the interaction of cancer and immune cells. A comprehensive understanding of these signalling processes is therefore essential to identify drug targets, plan clinical trials, and to select suitable drugs, drug combinations and drug dosages for a specific patient. Yet, most of the available mathematical models capture only a small number of molecular species and pathways, thereby ignoring important crosstalk and feedback loops. Furthermore, these models are usually based on experimental data for cell lines, which behave differently from complex cancer tissues.

In INTEGRATE, I will develop computational methods for the full process of data-driven modelling of signalling processes in cancer, ranging from model development to parameterisation all the way to uncertainty analysis. To this end, I will combine methods from the fields of mathematical modelling, machine learning, and signal processing with established approaches in systems biology. The model development will employ natural language processing and an automatic testing framework. For federated model inference, I will develop scalable mini-batch optimisation and marginalisation based uncertainty quantification. To refine models, I will exploit tools from signal processing, such as blind identification of latent variables. I will apply the developed scalable mechanistic modelling approach to integrate large-scale biomedical data for molecular phenotyping studies and clinical trials across sites. This will provide mechanistic models reconciling the available data.

The study will, for the first time, combine mechanistic modelling and machine learning for the integrated analysis of patient-derived omics and phenotypic data. By linking these data sources, INTEGRATE will deepen our understanding of biological signal processing and provide the basis for the development of digital twins.

Status

SIGNED

Call topic

ERC-2023-COG

Update Date

22-11-2024
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Horizon Europe
HORIZON.1 Excellent Science
HORIZON.1.1 European Research Council (ERC)
HORIZON.1.1.0 Cross-cutting call topics
ERC-2023-COG ERC CONSOLIDATOR GRANTS
HORIZON.1.1.1 Frontier science
ERC-2023-COG ERC CONSOLIDATOR GRANTS