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Evaluating valid parameter regimes for biocircuits

Liu, Q.; Xiao, F.

2026-01-21 synthetic biology
10.64898/2026.01.19.700491 bioRxiv
Show abstract

Biocircuits often realize their functions only within specific parameter regimes, yet identifying those regimes and quantifying how difficult they are to satisfy remain challenging. Powered by the recently developed Reaction Order Polyhedra (ROP) framework enabling a holistic analysis of the behavior in biomolecular networks, we are now able to analyze these questions in a systematic way. In this work, we use ROP to derive the conditions under which Hill-like behaviors and adaptation in enzymatic negative feedback biocircuits can emerge. We also introduce the Realizability Index (R-index), i.e. the volume fraction of valid parameter regions, to quantify how hard it is for a biocircuit to achieve a desired function. We envision ROP theory and the R-index as important components of a new validity-aware conceptual language for studying and designing functional biocircuits.

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