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Under review as a conference paper at ICLR 2027

Beyond Action Entropy: Quotient-Space Exploration for Genome-Scale Metabolic Model Repair

Abstract

Repairing scientific models from functional observations differs fundamentally from supervised prediction: feedback may certify a solution without revealing which structural correction is responsible. We study this setting for genome-scale metabolic model (GEM) repair, where multiple reaction edits can explain the same phenotypes and many apparently distinct edits correspond to the same biological mechanism. This many-to-one structure creates a hidden failure mode for conventional exploration: diversity in the output space need not translate into diversity of scientific hypotheses. We introduce **QuotientPO**, which collapses equivalent repairs into canonical mechanisms and optimizes exploration directly over the resulting quotient space. To make quotient exploration informative under finite rollouts, we derive a kernelized R\'enyi estimator that resolves graded crowding among distinct repair cores beyond coarse exact-match counts. On 2,212 held-out GEMs, QuotientPO improves Success@32 from 17.93% to 20.10% (+12.1% relative) while consistently increasing distinct successful-core discovery under the same sampling budget. These results establish quotient-space exploration as a principled approach to mechanism-level discovery under verifier-induced equivalence.

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