J 2022

Exploring attractor bifurcations in Boolean networks

BENEŠ, Nikola, Luboš BRIM, Jakub KADLECAJ, Samuel PASTVA, David ŠAFRÁNEK et. al.

Základní údaje

Originální název

Exploring attractor bifurcations in Boolean networks

Autoři

BENEŠ, Nikola (203 Česká republika, domácí), Luboš BRIM (203 Česká republika, domácí), Jakub KADLECAJ (703 Slovensko, domácí), Samuel PASTVA (703 Slovensko, domácí) a David ŠAFRÁNEK (203 Česká republika, garant, domácí)

Vydání

BMC Bioinformatics, 2022, 1471-2105

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10201 Computer sciences, information science, bioinformatics

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 3.000

Kód RIV

RIV/00216224:14330/22:00125836

Organizační jednotka

Fakulta informatiky

DOI

UT WoS

000793836800001

Klíčová slova anglicky

Boolean networks; Attractor bifurcation; Symbolic computation; Software tool; type-1 interferons

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 28. 3. 2023 10:53, RNDr. Pavel Šmerk, Ph.D.

Anotace

V originále

Background Boolean networks (BNs) provide an effective modelling formalism for various complex biochemical phenomena. Their long term behaviour is represented by attractors–subsets of the state space towards which the BN eventually converges. These are then typically linked to different biological phenotypes. Depending on various logical parameters, the structure and quality of attractors can undergo a significant change, known as a bifurcation. We present a methodology for analysing bifurcations in asynchronous parametrised Boolean networks. Results In this paper, we propose a computational framework employing advanced symbolic graph algorithms that enable the analysis of large networks with hundreds of Boolean variables. To visualise the results of this analysis, we developed a novel interactive presentation technique based on decision trees, allowing us to quickly uncover parameters crucial to the changes in the attractor landscape. As a whole, the methodology is implemented in our tool AEON. We evaluate the method’s applicability on a complex human cell signalling network describing the activity of type-1 interferons and related molecules interacting with SARS-COV-2 virion. In particular, the analysis focuses on explaining the potential suppressive role of the recently proposed drug molecule GRL0617 on replication of the virus. Conclusions The proposed method creates a working analogy to the concept of bifurcation analysis widely used in kinetic modelling to reveal the impact of parameters on the system’s stability. The important feature of our tool is its unique capability to work fast with large-scale networks with a relatively large extent of unknown information. The results obtained in the case study are in agreement with the recent biological findings.

Návaznosti

MUNI/A/1145/2021, interní kód MU
Název: Rozsáhlé výpočetní systémy: modely, aplikace a verifikace XI. (Akronym: SV-FI MAV XI.)
Investor: Masarykova univerzita, Rozsáhlé výpočetní systémy: modely, aplikace a verifikace XI.
MUNI/G/1771/2020, interní kód MU
Název: Computational reconstruction of mechanistic framework underlying receptor tyrosine kinase function in signal transduction (Akronym: FGFSIGMOD)
Investor: Masarykova univerzita, Computational reconstruction of mechanistic framework underlying receptor tyrosine kinase function in signal transduction, INTERDISCIPLINARY - Mezioborové výzkumné projekty