Exploring attractor bifurcations in Boolean networks

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14330%2F22%3A00125836" target="_blank" >RIV/00216224:14330/22:00125836 - isvavai.cz</a>

Výsledek na webu

<a href="https://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-022-04708-9" target="_blank" >https://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-022-04708-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12859-022-04708-9" target="_blank" >10.1186/s12859-022-04708-9</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Exploring attractor bifurcations in Boolean networks

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Exploring attractor bifurcations in Boolean networks

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10201 - Computer sciences, information science, bioinformathics (hardware development to be 2.2, social aspect to be 5.8)

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

BMC Bioinformatics

ISSN

1471-2105

e-ISSN

—

Svazek periodika

23

Číslo periodika v rámci svazku

173

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

18

Strana od-do

1-18

Kód UT WoS článku

000793836800001

EID výsledku v databázi Scopus

2-s2.0-85130638799