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Connor McShaffrey

Publications and source records attributed to Connor McShaffrey.

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Viability Space Decomposition: A geometric partition of survival outcomes in single- and multi-agent systems

What determines whether an organism or collective will survive under particular conditions? This question is asked across the life sciences when determining adaptive fit, developing efficacious treatments for diseases, and assessing the risks posed by ecological shifts. To aid their investigations, researchers employ models of agents which must respect particular constraints to remain alive. By constraining the dynamics of these agents to bounded viability regions, these models form a class of extended dynamical systems where transient dynamics can lead to death, making traditional attractors and separatrices insufficient for characterizing the global space of possible behaviors. To remedy this, we develop viability space decomposition, an analysis framework for ordinary differential equation models of agents with viability constraints. We first introduce the general theory, revealing how several new classes of manifolds (mortality, ordering, and collapse) permit a complete decomposition of state space into regions of qualitatively similar survival outcomes: a viability portrait. We then demonstrate the method by completely analyzing the global behavior of three models: a subcellular network, a behaving cell with the same physiology, and two coupled cell networks. Finally, we finish by discussing how the framework scales and future directions for its development and application.

q-bio.QM

Matters of Life and Death in Computational Cell Biology

Nearly all cell models explicitly or implicitly deal with the biophysical constraints that must be respected for life to persist. Despite this, there is almost no systematicity in how these constraints are implemented, and we lack a principled understanding of how cellular dynamics interact with them and how they originate in actual biology. Computational cell biology will only overcome these concerns once it treats the life-death boundary as a central concept, creating a theory of cellular viability. We lay the foundation for such a development by demonstrating how specific geometric structures can separate regions of qualitatively similar survival outcomes in our models, offering new global organizing principles for cell fate. We also argue that idealized models of emergent individuals offer a tractable way to begin understanding life's intrinsically generated limits.

q-bio.CB