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Interactome fate controllability

Conference of Franck Delaplace, University of Paris Saclay on Friday, June 25, 2021 within the framework of the Scientific Animation Committee -CAS

During the last decade, a large amount of data on sequence alterations and biomolecular profiles for many human diseases were collected. They open up challenging prospects on their use in diagnosis, disease pathogenesis and treatment discovery. However, overcoming this challenge is currently hindered by the difficulties in assessing the functional consequences of disease-associated sequence variants and understanding how phenotype is affected by the combined effect of the genomic alterations. Therefore, we need to explore novel theoretic framework emphasizing an integrative and holistic view of biological systems for properly describing their functionalities with their phenotypic consequences. To this end, the interactome provides an appropriate representation for deciphering biological functionalities based on macro-molecular interactions. Accordingly, diseases correspond to perturbations affecting the structure of the network. The challenge is thus to infer these topological actions for controlling the cell fate change. We propose a theoretical framework, called Boolean control network, modeling the control resulting of the application of the topological actions to the interactome dynamics. The inference is based on abductive principle deducing from the effects, the expected cell fate, the parsimonious topological actions to reach this fate. The modeling framework can be applied to a large number of biological situations related to the cell fate alteration. In the talk we discuss the fundamental aspects of this framework and its application to cancer.

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