scholarly journals Windowed Granger causal inference strategy improves discovery of gene regulatory networks

2018 ◽  
Vol 115 (9) ◽  
pp. 2252-2257 ◽  
Author(s):  
Justin D. Finkle ◽  
Jia J. Wu ◽  
Neda Bagheri

Accurate inference of regulatory networks from experimental data facilitates the rapid characterization and understanding of biological systems. High-throughput technologies can provide a wealth of time-series data to better interrogate the complex regulatory dynamics inherent to organisms, but many network inference strategies do not effectively use temporal information. We address this limitation by introducing Sliding Window Inference for Network Generation (SWING), a generalized framework that incorporates multivariate Granger causality to infer network structure from time-series data. SWING moves beyond existing Granger methods by generating windowed models that simultaneously evaluate multiple upstream regulators at several potential time delays. We demonstrate that SWING elucidates network structure with greater accuracy in both in silico and experimentally validated in vitro systems. We estimate the apparent time delays present in each system and demonstrate that SWING infers time-delayed, gene–gene interactions that are distinct from baseline methods. By providing a temporal framework to infer the underlying directed network topology, SWING generates testable hypotheses for gene–gene influences.

2004 ◽  
Vol 02 (04) ◽  
pp. 765-783 ◽  
Author(s):  
GUILLAUME BOURQUE ◽  
DAVID SANKOFF

We present a method for gene network inference and revision based on time-series data. Gene networks are modeled using linear differential equations and a generalized stepwise multiple linear regression procedure is used to recover the interaction coefficients. Our system is designed for the recovery of gene interactions concurrently in many gene regulatory networks related by a tree or a more general graph. We show how this comparative framework can facilitate the recovery of the networks and improve the quality of the solutions inferred.


Author(s):  
Christopher A. Penfold ◽  
Ahmed Shifaz ◽  
Paul E. Brown ◽  
Ann Nicholson ◽  
David L. Wild

AbstractHere we introduce the causal structure identification (CSI) package, a Gaussian process based approach to inferring gene regulatory networks (GRNs) from multiple time series data. The standard CSI approach infers a single GRN via joint learning from multiple time series datasets; the hierarchical approach (HCSI) infers a separate GRN for each dataset, albeit with the networks constrained to favor similar structures, allowing for the identification of context specific networks. The software is implemented in MATLAB and includes a graphical user interface (GUI) for user friendly inference. Finally the GUI can be connected to high performance computer clusters to facilitate analysis of large genomic datasets.


2020 ◽  
Vol 36 (19) ◽  
pp. 4885-4893 ◽  
Author(s):  
Baoshan Ma ◽  
Mingkun Fang ◽  
Xiangtian Jiao

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.


2016 ◽  
Vol 26 (4) ◽  
pp. 043102 ◽  
Author(s):  
E. Bianco-Martinez ◽  
N. Rubido ◽  
Ch. G. Antonopoulos ◽  
M. S. Baptista

2020 ◽  
Author(s):  
Michaël Pierrelée ◽  
Ana Reynders ◽  
Fabrice Lopez ◽  
Aziz Moqrich ◽  
Laurent Tichit ◽  
...  

Abstract Integrating -omics data with biological networks such as protein-protein interaction networks is a popular and useful approach to interpret expression changes of genes in changing conditions, and to identify relevant cellular pathways, active subnetworks or network communities. Yet, most -omics data integration tools are restricted to static networks and therefore cannot easily be used for analyzing time-series data. Determining regulations or exploring the network structure over time requires time-dependent networks which incorporate time as one component in their structure. Here, we present a method to project time-series data on sequential layers of a multilayer network, thus creating a temporal multilayer network (tMLN). We implemented this method as a Cytoscape app we named TimeNexus. TimeNexus allows to easily create, manage and visualize temporal multilayer networks starting from a combination of node and edge tables carrying the information on the temporal network structure. To allow further analysis of the tMLN, TimeNexus creates and passes on regular Cytoscape networks in form of static versions of the tMLN in three different ways: i) over the entire set of layers, ii) over two consecutive layers at a time, iii) or on one single layer at a time. We combined TimeNexus with the Cytoscape apps PathLinker and AnatApp/ANAT to extract active subnetworks from tMLNs. To test the usability of our app, we applied TimeNexus together with PathLinker or ANAT on temporal expression data of the yeast cell cycle and were able to identify active subnetworks relevant for different cell cycle phases. We furthermore used TimeNexus on our own temporal expression data from a mouse pain assay inducing hindpaw inflammation and detected active subnetworks relevant for an inflammatory response to injury, including immune response, cell stress response and regulation of apoptosis. TimeNexus is freely available from the Cytoscape app store at https://apps.cytoscape.org/apps/TimeNexus.


Author(s):  
Mara A. Freilich ◽  
Rolando Rebolledo ◽  
Derek Corcoran ◽  
Pablo A. Marquet

Ecosystems functioning is based on an intricate web of interactions among living entities. Most of these interactions are difficult to observe, especially when the diversity of interacting entities is large and they are of small size and abundance. To sidestep this limitation, it has become common to infer the network structure of ecosystems from time series of species abundance, but it is not clear how well can networks be reconstructed, especially in the presence of stochasticity that propagates through ecological networks. We evaluate the effects of intrinsic noise and network topology on the performance of different methods of inferring network structure from time-series data. Analysis of seven different four-species motifs using a stochastic model demonstrates that star-shaped motifs are differentially detected by these methods while rings are differentially constructed. The ability to reconstruct the network is unaffected by the magnitude of stochasticity in the population dynamics. Instead, interaction between the stochastic and deterministic parts of the system determines the path that the whole system takes to equilibrium and shapes the species covariance. We highlight the effects of long transients on the path to equilibrium and suggest a path forward for developing more ecologically sound statistical techniques.


2021 ◽  
Author(s):  
Marzieh Emadi ◽  
Farsad Zamani Boroujeni ◽  
jamshid Pirgazi

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.


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