FAMoS: A Flexible and dynamic Algorithm for Model Selection to analyse complex systems dynamics

Most biological systems are difficult to analyse due to a multitude of interacting components and the concomitant lack of information about the essential dynamics. Finding appropriate models that provide a systematic description of such biological systems and that help to identify their relevant factors and processes can be challenging given the sheer number of possibilities. Model selection algorithms that evaluate the performance of a multitude of different models against experimental data provide a useful tool to identify appropriate model structures. However, many algorithms addressing the analysis of complex dynamical systems, as they are often used in biology, compare a preselected number of models or rely on exhaustive searches of the total model space which might be unfeasible dependent on the number of possibilities. Therefore, we developed an algorithm that is able to perform model selection on complex systems and searches large model spaces in a dynamical way. Our algorithm includes local and newly developed non-local search methods that can prevent the algorithm from ending up in local minima of the model space by accounting for structurally similar processes. We tested and validated the algorithm based on simulated data and showed its flexibility for handling different model structures. We also used the algorithm to analyse experimental data on the cell proliferation dynamics of CD4+ and CD8+ T cells that were cultured under different conditions. Our analyses indicated dynamical changes within the proliferation potential of cells that was reduced within tissue-like 3D ex vivo cultures compared to suspension. Due to the flexibility in handling various model structures, the algorithm is applicable to a large variety of different biological problems and represents a useful tool for the data-oriented evaluation of complex model spaces.Author summary: Identifying the systematic interactions of multiple components within a complex biological system can be challenging due to the number of potential processes and the concomitant lack of information about the essential dynamics. Selection algorithms that allow an automated evaluation of a large number of different models provide a useful tool in identifying the systematic relationships between experimental data. However, many of the existing model selection algorithms are not able to address complex model structures, such as systems of differential equations, and partly rely on local or exhaustive search methods which are inappropriate for the analysis of various biological systems. Therefore, we developed a flexible model selection algorithm that performs a robust and dynamical search of large model spaces to identify complex systems dynamics and applied it to the analysis of T cell proliferation dynamics within different culture conditions. The algorithm, which is available as an R-package, provides an advanced tool for the analysis of complex systems behaviour and, due to its flexible structure, can be applied to a large variety of biological problems.