Dresden 2020 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 11: Data analytics for dynamical systems I (Focus Session joint with DY and BP) (joint session SOE/BP/CPP/DY)

BP 11.1: Topical Talk

Dienstag, 17. März 2020, 09:30–10:00, GÖR 226

One model to rule them all — •Jens Timmer — Institute of Physics, University of Freiburg, Germany

A major goal in systems biology is to reveal potential drug targets for cancer therapy. A common property of cancer cells is the alteration of signaling pathways triggering cell-fate decisions resulting in uncontrolled proliferation and tumor growth. However, addressing cancer-specific alterations experimentally by investigating each node in the signaling network one after the other is difficult or even not possible at all. Here, we use quantitative time-resolved data from different cell lines for non-linear modeling under L1 regularization, which is capable of detecting cell-type specific parameters. To adapt the least-squares numerical optimization routine to L1 regularization, sub-gradient strategies as well as truncation of proposed optimization steps were implemented. Likelihood-ratio tests were used to determine the optimal penalization strength resulting in a sparse solution in terms of a minimal number of cell-type specific parameters that is in agreement with the data. The uniqueness of the solution is investigated using the profile likelihood. Based on the minimal set of cell-type specific parameters experiments were designed for improving identifiability and to validate the model. The approach constitutes a general method to infer an overarching model with a minimum number of individual parameters for the particular models.