Efficient reduction of Kappa models by static inspection of the rule-set

DOI10.1007/978-3-319-26916-0_10zbMATH Open1412.92075arXiv1501.00440OpenAlexW2962791474MaRDI QIDQ5376909FDOQ5376909

Authors: Andreea Beica, Călin C. Guet, Tatjana Petrov 

Publication date: 21 May 2019

Published in: Hybrid Systems Biology (Search for Journal in Brave)

Abstract: When designing genetic circuits, the typical primitives used in major existing modelling formalisms are gene interaction graphs, where edges between genes denote either an activation or inhibition relation. However, when designing experiments, it is important to be precise about the low-level mechanistic details as to how each such relation is implemented. The rule-based modelling language Kappa allows to unambiguously specify mechanistic details such as DNA binding sites, dimerisation of transcription factors, or co-operative interactions. However, such a detailed description comes with complexity and computationally costly execution. We propose a general method for automatically transforming a rule-based program, by eliminating intermediate species and adjusting the rate constants accordingly. Our method consists of searching for those interaction patterns known to be amenable to equilibrium approximations (e.g. Michaelis-Menten scheme). The reduced model is efficiently obtained by static inspection over the rule-set, and it represents a particular theoretical limit of the original model. The Bhattacharyya distance is proposed as a metric to estimate the reduction error for a given observable. The tool is tested on a detailed rule-based model of a $lambda$-phage switch, which lists $96$ rules and $16$ agents. The reduced model has $11$ rules and $5$ agents, and provides a dramatic reduction in simulation time of several orders of magnitude.

Full work available at URL: https://arxiv.org/abs/1501.00440

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zbMATH Keywords

DNA binding sitesgene interaction graphsKappa model

Mathematics Subject Classification ID

Biochemistry, molecular biology (92C40) Computational methods for problems pertaining to biology (92-08)

Cited In (8)

• Tropical abstraction of biochemical reaction networks with guarantees
• Long lived transients in gene regulation
• Complete characterization for the fit-preserving data refinement of mass-action reaction networks
• Compact representation of photosynthesis dynamics by rule-based models
• Combining model reductions
• Formal reduction for rule-based models
• Automated deep abstractions for stochastic chemical reaction networks
• Modelling patterns of gene regulation in the bond-calculus

Uses Software

• KAPPA

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