Observable-Reduction-Guided Sparse Regression for Partially Observed Active-Quiescent Systems

Abstract

Active-quiescent switching occurs in biological populations in which growth is confined to a proliferative active state, while cells may reversibly enter a nonproliferative quiescent state. Experiments often observe only part of this process, through active-state markers, aggregate population measurements, or aggregate data supplemented by sparse active-state observations. Such measurements arise when marker panels are limited, active-state assays require fixation or endpoint sampling, or only total cell number, optical density, tumor burden, or aggregate fluorescence is reported. These observation choices complicate sparse regression methods such as sparse identification of nonlinear dynamics (SINDy), because the measured variable may satisfy a different equation from the underlying active-quiescent system. A library chosen for the wrong observable may therefore fit a trajectory without preserving mechanistic interpretation or transferability. We study this issue using a two-compartment ordinary differential equation model. We define observable reduction as the elimination of hidden states to obtain the differential equation satisfied by the measured variable. For several biologically relevant growth laws, we derive observation-specific reductions and use them to construct sparse-regression libraries. Using synthetic data, we compare these structured libraries with standard polynomial SINDy. Polynomial libraries can match training trajectories while failing coefficient-relation and transfer tests, whereas reduction-guided libraries recover interpretable coefficient maps when the observed regime is informative. These results show that interpretable equation learning in hidden-compartment systems requires matching both the regression target and candidate library to the observation process.