Inference and analysis of gene regulatory networks using data mining techniques

2020 ◽  
Vol 10 (1) ◽  
pp. 1-2
Author(s):  
Syed Sazzad Ahmed ◽  
Swarup Roy
2007 ◽  
Vol 05 (03) ◽  
pp. 651-668 ◽  
Author(s):  
PATRICK C. H. MA ◽  
KEITH C. C. CHAN

Recent development in DNA microarray technologies has made the reconstruction of gene regulatory networks (GRNs) feasible. To infer the overall structure of a GRN, there is a need to find out how the expression of each gene can be affected by the others. Many existing approaches to reconstructing GRNs are developed to generate hypotheses about the presence or absence of interactions between genes so that laboratory experiments can be performed afterwards for verification. Since, they are not intended to be used to predict if a gene in an unseen sample has any interactions with other genes, statistical verification of the reliability of the discovered interactions can be difficult. Furthermore, since the temporal ordering of the data is not taken into consideration, the directionality of regulation cannot be established using these existing techniques. To tackle these problems, we propose a data mining technique here. This technique makes use of a probabilistic inference approach to uncover interesting dependency relationships in noisy, high-dimensional time series expression data. It is not only able to determine if a gene is dependent on another but also whether or not it is activated or inhibited. In addition, it can predict how a gene would be affected by other genes even in unseen samples. For performance evaluation, the proposed technique has been tested with real expression data. Experimental results show that it can be very effective. The discovered dependency relationships can reveal gene regulatory relationships that could be used to infer the structures of GRNs.


Author(s):  
Nikolas Bernaola ◽  
Mario Michiels ◽  
Pedro Larrañaga ◽  
Concha Bielza

AbstractWe present FGES-Merge, a new method for learning the structure of gene regulatory networks via merging locally learned Bayesian networks, based on the fast greedy equivalent search algorithm. The method is competitive with the state of the art in terms of the recall of the true structure while also improving upon it in terms of speed, scaling up to the tens of thousands of variables and being able to use empirical knowledge about the topological structure of gene regulatory networks. We apply this method to learning the gene regulatory network for the full human genome using data from samples of different brain structures (from the Allen Human Brain Atlas). Our goal is to develop a Bayesian network model that predicts interactions between genes in a way that is clear to experts, following the current trends in interpretable artificial intelligence. To achieve this, we also present a new open-access visualization tool that facilitates the exploration of massive networks and can aid in finding nodes of interest for experimental tests.


2018 ◽  
Vol 34 (20) ◽  
pp. 3470-3478 ◽  
Author(s):  
Wenping Deng ◽  
Kui Zhang ◽  
Sanzhen Liu ◽  
Patrick X Zhao ◽  
Shizhong Xu ◽  
...  

2018 ◽  
Author(s):  
Claude Gérard ◽  
Mickaël Di-Luoffo ◽  
Léolo Gonay ◽  
Stefano Caruso ◽  
Gabrielle Couchy ◽  
...  

AbstractAlterations of individual genes variably affect development of hepatocellular carcinoma (HCC), prompting the need to characterize the function of tumor-promoting genes in the context of gene regulatory networks (GRN). Here, we identify a GRN which functionally links LIN28B-dependent dedifferentiation with dysfunction of CTNNB1 (β-CATENIN). LIN28B and CTNNB1 form a functional GRN with SMARCA4 (BRG1), Let-7b, SOX9, TP53 and MYC. GRN activity is detected in HCC and gastrointestinal cancers; it negatively correlates with HCC prognosis and contributes to a transcriptomic profile typical of the proliferative class of HCC. Using data from The Cancer Genome Atlas and from transcriptomic, transfection and mouse transgenic experiments, we generated and validated a quantitative mathematical model of the GRN. The model predicts how the expression of GRN components changes when the expression of another GRN member varies or is inhibited by a pharmacological drug. The dynamics of GRN component expression reveal distinct cell states that can switch reversibly in normal condition, and irreversibly in HCC. We conclude that identification and modelling of the GRN provides insight into prognosis, mechanisms of tumor-promoting genes and response to pharmacological agents in HCC.


2004 ◽  
Vol 381 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Gong-Hong WEI ◽  
De-Pei LIU ◽  
Chih-Chuan LIANG

One of the foremost challenges in the post-genomic era will be to chart the gene regulatory networks of cells, including aspects such as genome annotation, identification of cis-regulatory elements and transcription factors, information on protein–DNA and protein–protein interactions, and data mining and integration. Some of these broad sets of data have already been assembled for building networks of gene regulation. Even though these datasets are still far from comprehensive, and the approach faces many important and difficult challenges, some strategies have begun to make connections between disparate regulatory events and to foster new hypotheses. In this article we review several different genomics and proteomics technologies, and present bioinformatics methods for exploring these data in order to make novel discoveries.


2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Xin Lai ◽  
Animesh Bhattacharya ◽  
Ulf Schmitz ◽  
Manfred Kunz ◽  
Julio Vera ◽  
...  

MicroRNAs (miRNAs) are potent effectors in gene regulatory networks where aberrant miRNA expression can contribute to human diseases such as cancer. For a better understanding of the regulatory role of miRNAs in coordinating gene expression, we here present a systems biology approach combining data-driven modeling and model-driven experiments. Such an approach is characterized by an iterative process, including biological data acquisition and integration, network construction, mathematical modeling and experimental validation. To demonstrate the application of this approach, we adopt it to investigate mechanisms of collective repression on p21 by multiple miRNAs. We first construct a p21 regulatory network based on data from the literature and further expand it using algorithms that predict molecular interactions. Based on the network structure, a detailed mechanistic model is established and its parameter values are determined using data. Finally, the calibrated model is used to study the effect of different miRNA expression profiles and cooperative target regulation on p21 expression levels in different biological contexts.


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