Flux-species sampling enables holistic exploration of biocircuit behavior
Flux-species sampling enables holistic exploration of biocircuit behavior
Liu, Q.; Zhou, W.; Ren, X.; Marken, J. P.; Xiao, F.
AbstractBiocircuit behavior is usually discovered by drawing uncertain kinetic parameters and simulating, but the scored phenotypes are functions of steady-state species, catalytic fluxes, dominance relations, and local response matrices. We introduce flux-species sampling (FSS), which samples that functional layer directly and algebraically inverts to parameters. This coordinate change turns regulatory modes into simple dominance chambers, gives every full-dimensional behavior-realizing regime positive measure, and can replace the sampling stage of existing pipelines without changing downstream stability or phenotype tests. A sequestration toy shows how a large species regime can collapse into a narrow parameter strip. In an enzymatic feedback motif, FSS rescues free-A* adaptation missed by parameter sampling and identifies the regime as non-Michaelian and complex-dominated. In MultiFate-N, FSS separates a sampling limitation from a structural limitation and rescues parameter sets realizing all 2N states.