MOTIVATION: Interaction graphs are able to describe regulatory dependencies between compounds without capturing dynamics. In contrast, mathematical models that are based on interaction graphs allow to investigate the dynamics of biological systems. However, since dynamic complexity of these models grows exponentially with their size, exhaustive analyses of the dynamics and consequently screening all possible interventions eventually becomes infeasible. Thus, we designed an approach to identify dynamically relevant compounds based on the static network topology. RESULTS: Here, we present a method only based on static properties to identify dynamically influencing nodes. Coupling vertex betweenness and determinative power, we could capture relevant nodes for changing dynamics with an accuracy of 75% in a set of 35 published logical models. Further analyses of the selected compounds' connectivity unravelled a new class of not highly connected nodes with high impact on the networks' dynamics, which we call gatekeepers. We validated our method's working concept on logical models, which can be readily scaled up to complex interaction networks, where dynamic analyses are not even feasible. SUPPLEMENTARY INFORMATION: Supplementary data are available online. AVAILABILITY AND IMPLEMENTATION: Code is freely available at https://github.com/sysbio-bioinf/BNStatic.
MOTIVATION: Interaction graphs are able to describe regulatory dependencies between compounds without capturing dynamics. In contrast, mathematical models that are based on interaction graphs allow to investigate the dynamics of biological systems. However, since dynamic complexity of these models grows exponentially with their size, exhaustive analyses of the dynamics and consequently screening all possible interventions eventually becomes infeasible. Thus, we designed an approach to identify dynamically relevant compounds based on the static network topology. RESULTS: Here, we present a method only based on static properties to identify dynamically influencing nodes. Coupling vertex betweenness and determinative power, we could capture relevant nodes for changing dynamics with an accuracy of 75% in a set of 35 published logical models. Further analyses of the selected compounds' connectivity unravelled a new class of not highly connected nodes with high impact on the networks' dynamics, which we call gatekeepers. We validated our method's working concept on logical models, which can be readily scaled up to complex interaction networks, where dynamic analyses are not even feasible. SUPPLEMENTARY INFORMATION: Supplementary data are available online. AVAILABILITY AND IMPLEMENTATION: Code is freely available at https://github.com/sysbio-bioinf/BNStatic.
Authors: Felix M Weidner; Julian D Schwab; Silke D Werle; Nensi Ikonomi; Ludwig Lausser; Hans A Kestler Journal: Bioinformatics Date: 2022-05-13 Impact factor: 6.931
Authors: Silke D Werle; Nensi Ikonomi; Julian D Schwab; Johann M Kraus; Felix M Weidner; K Lenhard Rudolph; Astrid S Pfister; Rainer Schuler; Michael Kühl; Hans A Kestler Journal: Comput Struct Biotechnol J Date: 2022-04-02 Impact factor: 6.155