Epistasis on Networks

  • Research questions/goals:The biochemical and molecular mechanisms underlying epistatic phenomena observed in various living organisms are poorly understood. Epistasis, or genetic interactions, refers to functional relationships between genes. It describes the phenotypic effect of perturbing (e.g., knocking down or knocking out) two genes separately versus jointly relative to the unperturbed system. Thus, epistasis is a property of the underlying network of biochemical interactions in the cell.
    In this project, we use a mathematical framework linking epistatic gene interactions to the redundancy of biological networks. This approach is based on network reliability, an engineering concept that allows for computing the probability of functional network operation under different network perturbations, such as the failure of specific components, which, in a genetic system, correspond to the knock-out or knock-down of specific genes. Using this framework, we want to study how to infer functional constraints in biological networks from observed genetic interactions.
  • Current main results and/or publications: Preliminary work in collaboration with Prof. Dr. Niko Beerenwinkel (D-BSSE, ETH Zürich) led to a formal definition of epistasis in terms of network reliability. These initial steps are presented in a book chapter contained in the book Systems Genetics, Linking Genotypes and Phenotypes, edited by Dr. Florian Markowetz and Prof. Dr. Michael Boutros.
  • Collaborators: Dr. Michael Shapiro at the Francis Crick Institute, London, UK.