scholarly journals A survey of gene regulatory networks modelling methods: from differential equations, to Boolean and qualitative bioinspired models

2020 ◽  
Vol 2 (3) ◽  
pp. 207-226 ◽  
Author(s):  
Roberto Barbuti ◽  
Roberta Gori ◽  
Paolo Milazzo ◽  
Lucia Nasti
Keyword(s):  
Differential Equations ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Quantitative Methods ◽  
Environmental Changes ◽  
Boolean Networks ◽  
Specific Cell ◽  
Qualitative Approaches ◽  
Gene Regulatory ◽  
Gillespie’S Algorithm

Abstract Gene Regulatory Networks (GRNs) represent the interactions among genes regulating the activation of specific cell functionalities, such as reception of (chemical) signals or reaction to environmental changes. Studying and understanding these processes is crucial: they are the fundamental mechanism at the basis of cell functioning, and many diseases are based on perturbations or malfunctioning of some gene regulation activities. In this paper, we provide an overview on computational approaches to GRN modelling and analysis. We start from the biological and quantitative modelling background notions, recalling differential equations and the Gillespie’s algorithm. Then, we describe more in depth qualitative approaches such as Boolean networks and some computer science formalisms, including Petri nets, P systems and reaction systems. Our aim is to introduce the reader to the problem of GRN modelling and to guide her/him along the path that goes from classical quantitative methods, through qualitative methods based on Boolean network, up to some of the most relevant qualitative computational methods to understand the advantages and limitations of the different approaches.

Encoding Threshold Boolean Networks into Reaction Systems for the Analysis of Gene Regulatory Networks

2021 ◽  
Vol 179 (2) ◽  
pp. 205-225
Author(s):  
Roberto Barbuti ◽  
Pasquale Bove ◽  
Roberta Gori ◽  
Damas Gruska ◽  
Francesca Levi ◽  
...  
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Boolean Network ◽  
Reaction System ◽  
Boolean Networks ◽  
Specific Cell ◽  
Reaction Systems ◽  
Gene Regulatory ◽  
Closed Reaction System

Gene regulatory networks represent the interactions among genes regulating the activation of specific cell functionalities and they have been successfully modeled using threshold Boolean networks. In this paper we propose a systematic translation of threshold Boolean networks into reaction systems. Our translation produces a non redundant set of rules with a minimal number of objects. This translation allows us to simulate the behavior of a Boolean network simply by executing the (closed) reaction system we obtain. This can be very useful for investigating the role of different genes simply by “playing” with the rules. We developed a tool able to systematically translate a threshold Boolean network into a reaction system. We use our tool to translate two well known Boolean networks modelling biological systems: the yeast-cell cycle and the SOS response in Escherichia coli. The resulting reaction systems can be used for investigating dynamic causalities among genes.

Inference of gene regulatory networks based on nonlinear ordinary differential equations

2020 ◽  
Vol 36 (19) ◽  
pp. 4885-4893 ◽  
Author(s):  
Baoshan Ma ◽  
Mingkun Fang ◽  
Xiangtian Jiao
Keyword(s):  
Gene Expression ◽  
Time Series ◽  
Steady State ◽  
Differential Equations ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Time Series Data ◽  
Series Data ◽  
State Data ◽  
Gene Regulatory

Abstract Motivation Gene regulatory networks (GRNs) capture the regulatory interactions between genes, resulting from the fundamental biological process of transcription and translation. In some cases, the topology of GRNs is not known, and has to be inferred from gene expression data. Most of the existing GRNs reconstruction algorithms are either applied to time-series data or steady-state data. Although time-series data include more information about the system dynamics, steady-state data imply stability of the underlying regulatory networks. Results In this article, we propose a method for inferring GRNs from time-series and steady-state data jointly. We make use of a non-linear ordinary differential equations framework to model dynamic gene regulation and an importance measurement strategy to infer all putative regulatory links efficiently. The proposed method is evaluated extensively on the artificial DREAM4 dataset and two real gene expression datasets of yeast and Escherichia coli. Based on public benchmark datasets, the proposed method outperforms other popular inference algorithms in terms of overall score. By comparing the performance on the datasets with different scales, the results show that our method still keeps good robustness and accuracy at a low computational complexity. Availability and implementation The proposed method is written in the Python language, and is available at: https://github.com/lab319/GRNs_nonlinear_ODEs Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Modelling Three Dimensional Gene Regulatory Networks

2021 ◽  
Vol 16 ◽  
pp. 755-763
Author(s):  
Inna Samuilik ◽  
Felix Sadyrbaev
Keyword(s):  
Differential Equations ◽  
Gene Regulatory Networks ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Linear Part ◽  
Three Dimensional ◽  
Special Kind ◽  
Sigmoidal Function ◽  
Solution Vector ◽  
Gene Regulatory

We consider the three-dimensional gene regulatory network (GRN in short). This model consists of ordinary differential equations of a special kind, where the nonlinearity is represented by a sigmoidal function and the linear part is present also. The evolution of GRN is described by the solution vector X(t), depending on time. We describe the changes that system undergoes if the entries of the regulatory matrix are perturbed in some way.

scholarly journals A Nullclines Approach to the Study of 2D Artificial Network

2019 ◽  
Vol 1 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Felikss Sadirbajevs
Keyword(s):  
Vector Field ◽  
Differential Equations ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Field Analysis ◽  
Geometrical Approach ◽  
Full Generality ◽  
First Order ◽  
Gene Regulatory ◽  
Artificial Network

The system of two the first order ordinary differential equations arising in the gene regulatory networks theory is studied. The structure of attractors for this system is described for three important behavioral cases: activation, inhibition, mixed activation-inhibition. The geometrical approach combined with the vector field analysis allows treating the problem in full generality. A number of propositions are stated and the proof is geometrical, avoiding complex analytic. Although not all the possible cases are considered, the instructions are given what to do in any particular situation.

Improved Fuzzy Cognitive Maps for Gene Regulatory Networks Inference Based on Time Series Data

2021 ◽  
Author(s):  
Marzieh Emadi ◽  
Farsad Zamani Boroujeni ◽  
jamshid Pirgazi
Keyword(s):  
Time Series ◽  
Compressed Sensing ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Time Series Data ◽  
Cognitive Maps ◽  
Boolean Networks ◽  
Fuzzy Cognitive Maps ◽  
Series Data ◽  
Gene Regulatory

Abstract Recently with the advancement of high-throughput sequencing, gene regulatory network inference has turned into an interesting subject in bioinformatics and system biology. But there are many challenges in the field such as noisy data, uncertainty, time-series data with numerous gene numbers and low data, time complexity and so on. In recent years, many research works have been conducted to tackle these challenges, resulting in different methods in gene regulatory networks inference. A number of models have been used in modeling of the gene regulatory networks including Boolean networks, Bayesian networks, Markov model, relational networks, state space model, differential equations model, artificial neural networks and so on. In this paper, the fuzzy cognitive maps are used to model gene regulatory networks because of their dynamic nature and learning capabilities for handling non-linearity and inherent uncertainty. Fuzzy cognitive maps belong to the family of recurrent networks and are well-suited for gene regulatory networks. In this research study, the Kalman filtered compressed sensing is used to infer the fuzzy cognitive map for the gene regulatory networks. This approach, using the advantages of compressed sensing and Kalman filters, allows robustness to noise and learning of sparse gene regulatory networks from data with high gene number and low samples. In the proposed method, stream data and previous knowledge can be used in the inference process. Furthermore, compressed sensing finds likely edges and Kalman filter estimates their weights. The proposed approach uses a novel method to decrease the noise of data. The proposed method is compared to CSFCM, LASSOFCM, KFRegular, ABC, RCGA, ICLA, and CMI2NI. The results show that the proposed approach is superior to the other approaches in fuzzy cognitive maps learning. This behavior is related to the stability against noise and offers a proper balance between data error and network structure.

scholarly journals SYMBOLIC APPROACHES FOR FINDING CONTROL STRATEGIES IN BOOLEAN NETWORKS

2009 ◽  
Vol 07 (02) ◽  
pp. 323-338 ◽  
Author(s):  
CHRISTOPHER JAMES LANGMEAD ◽  
SUMIT KUMAR JHA
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Transfer Functions ◽  
Control Strategies ◽  
Exact Algorithm ◽  
Boolean Networks ◽  
Qualitative Behavior ◽  
Control Policies ◽  
Target Time ◽  
Gene Regulatory

We present an exact algorithm, based on techniques from the field of Model Checking, for finding control policies for Boolean Networks (BN) with control nodes. Given a BN, a set of starting states, I, a set of goal states, F, and a target time, t, our algorithm automatically finds a sequence of control signals that deterministically drives the BN from I to F at, or before time t, or else guarantees that no such policy exists. Despite recent hardness-results for finding control policies for BNs, we show that, in practice, our algorithm runs in seconds to minutes on over 13,400 BNs of varying sizes and topologies, including a BN model of embryogenesis in Drosophila melanogaster with 15,360 Boolean variables. We then extend our method to automatically identify a set of Boolean transfer functions that reproduce the qualitative behavior of gene regulatory networks. Specifically, we automatically learn a BN model of D. melanogaster embryogenesis in 5.3 seconds, from a space containing 6.9 × 1010 possible models.

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