Temporary and Permanent Control of Partially Specified Boolean Networks

BRIM, Luboš, Samuel PASTVA, David ŠAFRÁNEK and Eva ŠMIJÁKOVÁ. Temporary and Permanent Control of Partially Specified Boolean Networks. BIOSYSTEMS. Elsevier, 2023, vol. 223, JAN, p. 104795-104808. ISSN 0303-2647. Available from: https://dx.doi.org/10.1016/j.biosystems.2022.104795.

Basic information

• Original name: Temporary and Permanent Control of Partially Specified Boolean Networks
• Authors: BRIM, Luboš (203 Czech Republic, belonging to the institution), Samuel PASTVA (703 Slovakia, belonging to the institution), David ŠAFRÁNEK (203 Czech Republic, guarantor, belonging to the institution) and Eva ŠMIJÁKOVÁ (703 Slovakia, belonging to the institution).
• Edition: BIOSYSTEMS, Elsevier, 2023, 0303-2647.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10201 Computer sciences, information science, bioinformatics
• Country of publisher: Ireland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 1.600 in 2022
• RIV identification code: RIV/00216224:14330/23:00130043
• Organization unit: Faculty of Informatics
• Doi: http://dx.doi.org/10.1016/j.biosystems.2022.104795
• UT WoS: 000890559900005
• Keywords in English: Boolean network; Perturbation; Temporary Control; Permanent Control; Symbolic Algorithm
• Tags: International impact, Reviewed

Abstract

Boolean networks (BNs) are a well-accepted modelling formalism in computational systems biology. Neverthe-less, modellers often cannot identify only a single BN that matches the biological reality. The typical reasons for this is insufficient knowledge or a lack of experimental data. Formally, this uncertainty can be expressed using partially specified Boolean networks (PSBNs), which encode the wide range of network candidates into a single structure. In this paper, we target the control of PSBNs. The goal of BN control is to find perturbations which guarantee stabilisation of the system in the desired state. Specifically, we consider variable perturbations (gene knock-out and over-expression) with three types of application time-window: one-step, temporary, and permanent. While the control of fully specified BNs is a thoroughly explored topic, control of PSBNs introduces additional challenges that we address in this paper. In particular, the unspecified components of the model cause a significant amount of additional state space explosion. To address this issue, we propose a fully symbolic methodology that can represent the numerous system variants in a compact form. In fully specified models, the efficiency of a perturbation is characterised by the count of perturbed variables (the perturbation size). However, in the case of a PSBN, a perturbation might work only for a subset of concrete BN models. To that end, we introduce and quantify perturbation robustness. This metric characterises how efficient the given perturbation is with respect to the model uncertainty. Finally, we evaluate the novel control methods using non-trivial real-world PSBN models. We inspect the method's scalability and efficiency with respect to the size of the state space and the number of unspecified components. We also compare the robustness metrics for all three perturbation types. Our experiments support the hypothesis that one-step perturbations are significantly less robust than temporary and permanent ones.

Links

• GA22-10845S, research and development project: Name: Studium role polyhydroxyalkanoátů u bakterie Schlegelella thermodepolymerans – slibného bakteriálního kandidáta pro biotechnologie nové generace (Acronym: PHAST)

Investor: Czech Science Foundation, Unraveling the role of polyhydroxyalkanoates in Schlegelella thermodepolymerans – promising environmental bacterium for next generation biotechnology

• MUNI/A/1081/2022, interní kód MU: Name: Modelování, analýza a verifikace (2023)

Investor: Masaryk University