[HTML][HTML] Identification of dynamic driver sets controlling phenotypical landscapes

SD Werle, N Ikonomi, JD Schwab, JM Kraus… - Computational and …, 2022 - Elsevier
SD Werle, N Ikonomi, JD Schwab, JM Kraus, FM Weidner, KL Rudolph, AS Pfister, R Schuler
Computational and Structural Biotechnology Journal, 2022Elsevier
Controlling phenotypical landscapes is of vital interest to modern biology. This task becomes
highly demanding because cellular decisions involve complex networks engaging in
crosstalk interactions. Previous work on control theory indicates that small sets of
compounds can control single phenotypes. However, a dynamic approach is missing to
determine the drivers of the whole network dynamics. By analyzing 35 biologically motivated
Boolean networks, we developed a method to identify small sets of compounds sufficient to …
Abstract
Controlling phenotypical landscapes is of vital interest to modern biology. This task becomes highly demanding because cellular decisions involve complex networks engaging in crosstalk interactions. Previous work on control theory indicates that small sets of compounds can control single phenotypes. However, a dynamic approach is missing to determine the drivers of the whole network dynamics. By analyzing 35 biologically motivated Boolean networks, we developed a method to identify small sets of compounds sufficient to decide on the entire phenotypical landscape. These compounds do not strictly prefer highly related compounds and show a smaller impact on the stability of the attractor landscape. The dynamic driver sets include many intervention targets and cellular reprogramming drivers in human networks. Finally, by using a new comprehensive model of colorectal cancer, we provide a complete workflow on how to implement our approach to shift from in silico to in vitro guided experiments.
Elsevier
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