A prior knowledge based approach to infer gene regulatory networks

Author(s):  
Md. Mahmudul Hasan ◽  
Nasimul Noman ◽  
Hitoshi Iba
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.


Author(s):  
Aurelien Dugourd ◽  
Christoph Kuppe ◽  
Marco Sciacovelli ◽  
Enio Gjerga ◽  
Kristina B. Emdal ◽  
...  

AbstractMulti-omics datasets can provide molecular insights beyond the sum of individual omics. Diverse tools have been recently developed to integrate such datasets, but there are limited strategies to systematically extract mechanistic hypotheses from them. Here, we present COSMOS (Causal Oriented Search of Multi-Omics Space), a method that integrates phosphoproteomics, transcriptomics, and metabolics datasets. COSMOS combines extensive prior knowledge of signaling, metabolic, and gene regulatory networks with computational methods to estimate activities of transcription factors and kinases as well as network-level causal reasoning. COSMOS provides mechanistic hypotheses for experimental observations across multi-omics datasets. We applied COSMOS to a dataset comprising transcriptomics, phosphoproteomics, and metabolomics data from healthy and cancerous tissue from nine renal cell carcinoma patients. We used COSMOS to generate novel hypotheses such as the impact of Androgen Receptor on nucleoside metabolism and the influence of the JAK-STAT pathway on propionyl coenzyme A production. We expect that our freely available method will be broadly useful to extract mechanistic insights from multi-omics studies.Abstract Figure


2019 ◽  
Author(s):  
Kyung Dae Ko ◽  
Stefania Dell’Orso ◽  
Aster H. Juan ◽  
Vittorio Sartorelli

SUMMARYSingle-cell RNA-seq permits the characterization of the molecular expression states of individual cells. Several methods have been developed to spatially and temporally resolve individual cell populations. However, these methods are not always integrated and some of them are constrained by prior knowledge. Here, we present an integrated pipeline for inference of gene regulatory networks. The pipeline does not rely on prior knowledge, it improves inference accuracy by integrating signatures from different data dimensions and facilitates tracing variation of gene expression by visualizing gene-interacting patterns of co-expressed gene regulatory networks at distinct developmental stages.


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.


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