scholarly journals Reconstructing Gene Regulatory Networks with Bayesian Networks by Combining Expression Data with Multiple Sources of Prior Knowledge

Author(s):  
Adriano V Werhli ◽  
Dirk Husmeier

There have been various attempts to reconstruct gene regulatory networks from microarray expression data in the past. However, owing to the limited amount of independent experimental conditions and noise inherent in the measurements, the results have been rather modest so far. For this reason it seems advisable to include biological prior knowledge, related, for instance, to transcription factor binding locations in promoter regions or partially known signalling pathways from the literature. In the present paper, we consider a Bayesian approach to systematically integrate expression data with multiple sources of prior knowledge. Each source is encoded via a separate energy function, from which a prior distribution over network structures in the form of a Gibbs distribution is constructed. The hyperparameters associated with the different sources of prior knowledge, which measure the influence of the respective prior relative to the data, are sampled from the posterior distribution with MCMC. We have evaluated the proposed scheme on the yeast cell cycle and the Raf signalling pathway. Our findings quantify to what extent the inclusion of independent prior knowledge improves the network reconstruction accuracy, and the values of the hyperparameters inferred with the proposed scheme were found to be close to optimal with respect to minimizing the reconstruction error.

2021 ◽  
Author(s):  
Hakimeh Khojasteh ◽  
Mohammad Hossein Olyaee ◽  
Alireza Khanteymoori

The development of computational methods to predict gene regulatory networks (GRNs) from gene expression data is a challenging task. Many machine learning methods have been developed, including supervised, unsupervised, and semi-supervised to infer gene regulatory networks. Most of these methods ignore the class imbalance problem which can lead to decreasing the accuracy of predicting regulatory interactions in the network. Therefore, developing an effective method considering imbalanced data is a challenging task. In this paper, we propose EnGRNT approach to infer GRNs with high accuracy that uses ensemble-based methods. The proposed approach, as well as the gene expression data, considers the topological features of GRN. We applied our approach to the simulated Escherichia coli dataset. Experimental results demonstrate that the appropriateness of the inference method relies on the size and type of expression profiles in microarray data. Except for multifactorial experimental conditions, the proposed approach outperforms unsupervised methods. The obtained results recommend the application of EnGRNT on the imbalanced datasets.


Author(s):  
Luis M. de Campos ◽  
Andrés Cano ◽  
Javier G. Castellano ◽  
Serafín Moral

Abstract Gene Regulatory Networks (GRNs) are known as the most adequate instrument to provide a clear insight and understanding of the cellular systems. One of the most successful techniques to reconstruct GRNs using gene expression data is Bayesian networks (BN) which have proven to be an ideal approach for heterogeneous data integration in the learning process. Nevertheless, the incorporation of prior knowledge has been achieved by using prior beliefs or by using networks as a starting point in the search process. In this work, the utilization of different kinds of structural restrictions within algorithms for learning BNs from gene expression data is considered. These restrictions will codify prior knowledge, in such a way that a BN should satisfy them. Therefore, one aim of this work is to make a detailed review on the use of prior knowledge and gene expression data to inferring GRNs from BNs, but the major purpose in this paper is to research whether the structural learning algorithms for BNs from expression data can achieve better outcomes exploiting this prior knowledge with the use of structural restrictions. In the experimental study, it is shown that this new way to incorporate prior knowledge leads us to achieve better reverse-engineered networks.


2008 ◽  
Vol 06 (03) ◽  
pp. 543-572 ◽  
Author(s):  
ADRIANO V. WERHLI ◽  
DIRK HUSMEIER

There have been various attempts to improve the reconstruction of gene regulatory networks from microarray data by the systematic integration of biological prior knowledge. Our approach is based on pioneering work by Imoto et al.11 where the prior knowledge is expressed in terms of energy functions, from which a prior distribution over network structures is obtained in the form of a Gibbs distribution. The hyperparameters of this distribution represent the weights associated with the prior knowledge relative to the data. We have derived and tested a Markov chain Monte Carlo (MCMC) scheme for sampling networks and hyperparameters simultaneously from the posterior distribution, thereby automatically learning how to trade off information from the prior knowledge and the data. We have extended this approach to a Bayesian coupling scheme for learning gene regulatory networks from a combination of related data sets, which were obtained under different experimental conditions and are therefore potentially associated with different active subpathways. The proposed coupling scheme is a compromise between (1) learning networks from the different subsets separately, whereby no information between the different experiments is shared; and (2) learning networks from a monolithic fusion of the individual data sets, which does not provide any mechanism for uncovering differences between the network structures associated with the different experimental conditions. We have assessed the viability of all proposed methods on data related to the Raf signaling pathway, generated both synthetically and in cytometry experiments.


2020 ◽  
Author(s):  
Yijie Wang ◽  
Justin M Fear ◽  
Isabelle Berger ◽  
Hangnoh Lee ◽  
Brian Oliver ◽  
...  

AbstractGene Regulatory Networks (GRNs) control many aspects of cellular processes including cell differentiation, maintenance of cell type specific states, signal transduction, and response to stress. Since GRNs provide information that is essential for understanding cell function, the inference of these networks is one of the key challenges in systems biology. Leading algorithms to reconstruct GRN utilize, in addition to gene expression data, prior knowledge such as Transcription Factor (TF) DNA binding motifs or results of DNA binding experiments. However, such prior knowledge is typically incomplete hence resulting in missing values. Therefore, the integration of such incomplete prior knowledge with gene expression to elucidate the underlying GRNs remains difficult.To address this challenge we introduce NetREX-CF – Regulatory Network Reconstruction using EXpression and Collaborative Filtering – a GRN reconstruction approach that brings together a modern machine learning strategy (Collaborative Filtering model) and a biologically justified model of gene expression (sparse Network Component Analysis based model). The Collaborative Filtering (CF) model is able to overcome the incompleteness of the prior knowledge and make edge recommends for building the GRN. Complementing CF, the sparse Network Component Analysis (NCA) model can use gene expression data to validate the recommended edges. Here we combine these two approaches using a novel data integration method and show that the new approach outperforms the currently leading GRN reconstruction methods.Furthermore, our mathematical formalization of the model has lead to a complex optimization problem of a type that has not been attempted before. Specifically, the formulation contains ℓ0 norm that can not be separated from other variables. To fill this gap, we introduce here a new method Generalized PALM (GPALM) that allows us to solve a broad class of non-convex optimization problems and prove its convergence.


RSC Advances ◽  
2017 ◽  
Vol 7 (37) ◽  
pp. 23222-23233 ◽  
Author(s):  
Wei Liu ◽  
Wen Zhu ◽  
Bo Liao ◽  
Haowen Chen ◽  
Siqi Ren ◽  
...  

Inferring gene regulatory networks from expression data is a central problem in systems biology.


Biotechnology ◽  
2019 ◽  
pp. 265-304
Author(s):  
David Correa Martins Jr. ◽  
Fabricio Martins Lopes ◽  
Shubhra Sankar Ray

The inference of Gene Regulatory Networks (GRNs) is a very challenging problem which has attracted increasing attention since the development of high-throughput sequencing and gene expression measurement technologies. Many models and algorithms have been developed to identify GRNs using mainly gene expression profile as data source. As the gene expression data usually has limited number of samples and inherent noise, the integration of gene expression with several other sources of information can be vital for accurately inferring GRNs. For instance, some prior information about the overall topological structure of the GRN can guide inference techniques toward better results. In addition to gene expression data, recently biological information from heterogeneous data sources have been integrated by GRN inference methods as well. The objective of this chapter is to present an overview of GRN inference models and techniques with focus on incorporation of prior information such as, global and local topological features and integration of several heterogeneous data sources.


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