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SMT with Uninterpreted Functions and Monotonicity Constraints in Systems Biology

Authors: Ondřej Huvar, Martin Jonáš, and Samuel Pastva

Published in: LIPIcs, Volume 377, 29th International Conference on Theory and Applications of Satisfiability Testing (SAT 2026)


Abstract
Uninterpreted functions are a key modeling tool for systems with unknown or abstracted components. Certain domains, such as systems biology, additionally impose monotonicity constraints on these components, requiring specific inputs to have a consistently positive or negative effect on the output. In this paper, we tackle the model inference problem for biological systems by applying the theory of uninterpreted functions with monotonicity constraints. We compare the performance of naive quantified encodings of the problem and the performance of the existing approach based on eager quantifier instantiation, which is based on the fact that a finite set of quantifier-free monotonicity lemmas is sufficient to encode the monotonicity of uninterpreted functions. Additionally, we consider a lazy variant of the approach that introduces the monotonicity lemmas on demand. We evaluate the SMT-based approach to model inference using a large collection of systems biology benchmarks. The results demonstrate that the instantiation-based encodings significantly outperform quantified encodings, which typically struggle with large function arities and complex instances. As the key result, we show that our approach based on SMT with uninterpreted functions and monotonicity constraints significantly outperforms state-of-the-art domain-specific tools used in systems biology, such as the ASP-based Bonesis and the BDD-based AEON.

Cite as

Ondřej Huvar, Martin Jonáš, and Samuel Pastva. SMT with Uninterpreted Functions and Monotonicity Constraints in Systems Biology. In 29th International Conference on Theory and Applications of Satisfiability Testing (SAT 2026). Leibniz International Proceedings in Informatics (LIPIcs), Volume 377, pp. 19:1-19:18, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2026)


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@InProceedings{huvar_et_al:LIPIcs.SAT.2026.19,
  author =	{Huvar, Ond\v{r}ej and Jon\'{a}\v{s}, Martin and Pastva, Samuel},
  title =	{{SMT with Uninterpreted Functions and Monotonicity Constraints in Systems Biology}},
  booktitle =	{29th International Conference on Theory and Applications of Satisfiability Testing (SAT 2026)},
  pages =	{19:1--19:18},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-431-4},
  ISSN =	{1868-8969},
  year =	{2026},
  volume =	{377},
  editor =	{Ignatiev, Alexey and Szeider, Stefan},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.SAT.2026.19},
  URN =		{urn:nbn:de:0030-drops-263251},
  doi =		{10.4230/LIPIcs.SAT.2026.19},
  annote =	{Keywords: satisfiability modulo theories, uninterpreted function, monotonicity, boolean network, logic-based modeling}
}
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