Computational prediction of molecular pathogen-host interactions based on dual transcriptome data.

Inference of gene regulatory network from microarray data is one of the most important issues in bioinformatics. Several algorithms have been introduced for this problem, but they cannot give accurate results in case of time series gene expression data. Here, we propose an algorithm that predicts the gene regulatory network more accurately than the previous methods. A new method finds the relationship between a pair of genes by time-shifting the time series data of one gene against another when we compare the patterns of the gene pair. In addition, we increase the accuracy of the prediction method by filtering out the interactions that cannot exist in real biological network. We tested the algorithm to several simulated data which are based on realistic enzyme kinetics system, and evaluated the effectiveness of our algorithm. Results show that the present algorithm significantly improves the accuracy of the inference of gene regulatory network.

Enabled by recent advances in bioinformatics, the inference of gene regulatory networks (GRNs) from gene expression data has garnered much interest from researchers. This is due to the need of researchers to understand the dynamic behavior and uncover the vast information lay hidden within the networks. In this regard, dynamic Bayesian network (DBN) is extensively used to infer GRNs due to its ability to handle time-series microarray data and modeling feedback loops. However, the efficiency of DBN in inferring GRNs is often hampered by missing values in expression data, and excessive computation time due to the large search space whereby DBN treats all genes as potential regulators for a target gene. In this paper, we proposed a DBN-based model with missing values imputation to improve inference efficiency, and potential regulators detection which aims to lessen computation time by limiting potential regulators based on expression changes. The performance of the proposed model is assessed by using time-series expression data of yeast cell cycle. The experimental results showed reduced computation time and improved efficiency in detecting gene-gene relationships.KeywordsDynamic Bayesian NetworkGene Regulatory NetworksGene Expression DataInference

A new multiple regression approach for the construction of genetic regulatory networks

Gene Regulatory Networks (GRNs) inference from gene expression data is a hard task and a widely addressed challenge. GRNs can be represented as Boolean models similarly to digital circuits. Cartesian Genetic Programming (CGP), often used for designing circuits, can thus be adopted in the inference of GRNs. The main CGP operator for generating candidate designs is mutation, making its choice important for obtaining good results. Although there are many mutation operators for CGP, to the best of our knowledge, there is no analysis of them in the GRN inference problem. An evaluation of the Single ActiveMutation (SAM) and the Semantically-Oriented Mutation Operator (SOMO)is performed here for GRNs inference. Also, a combination of both operators is proposed. We use a benchmark single-cell RNA-Sequencingtime series data and its evaluation pipeline to measure the performance of the approaches. The experiments indicate that (i) combining SOMOand SAM provides the best results, and (ii) the results obtained by the proposal are competitive with those from state-of-the-art methods.

The inference of Gene Regulatory Networks (GRNs) from gene expression data is a hard and widely addressed scientific challenge with potential industrial and health-care use. Discrete and continuous models of GRNs are often used (i) to understand the process, and (ii) to predict the values of the relevant variables. Here, we propose a procedure to infer models of GRNs from data where (i) the data is binarized, (ii) a Boolean model is created using a Cartesian Genetic Programming technique, (iii) the obtained Boolean model is converted to a system of ordinary differential equations, and (iv) an Evolution Strategy defines the parameters of the continuous model. As a result, we expect to reduce the effect of noise and to improve biological interpretability. The proposed method is applied to two ODE systems that describe the circadian rhythm network dynamic, with 5 and 10 state variables. The models created by the proposed procedure are able to reproduce the behavior observed in the original data.

In this study, in order to deal with the noise and uncertainty in gene expression data, learning networks, especially Bayesian networks, that have the ability to use prior knowledge, were used to infer gene regulatory network. Learning networks are methods that have the structure of the network and a learning process to obtain relationships. One of the methods which have been used for measuring the relationship between genes is the correlation metrics, but the high correlated genes not necessarily mean that they have causal effect on each other. Studies on common methods in inference of gene regulatory networks are yet to pay attention to their biological importance and as such, predictions by these methods are less accurate in terms of biological significance. Hence, in the proposed method, genes with high correlation were identified in one cluster using clustering, and the existence of edge between the genes in the cluster was prevented. Finally, after the Bayesian network modeling, based on knowledge gained from clustering, the refining phase and improving regulatory interactions using biological correlation were done. In order to show the efficiency, the proposed method has been compared with several common methods in this area including GENIE3 and BMALR. The results of the evaluation indicate that the proposed method recognized regulatory relations in Bayesian modeling process well, due to using of biological knowledge which is hidden in the data collection, and is able to recognize gene regulatory networks align with important methods in this field.

Gene regulatory networks (GRNs) are crucial to understand the inner workings of the cell and the complexity of gene interactions. Numerous algorithms have been developed to infer GRNs from gene expression data. As the number of identified genes increases and the complexity of their interactions is uncovered, gene networks become cumbersome to test. Furthermore, prodding through experimental results requires an enormous amount of computation, resulting in slow data processing. Therefore, new approaches are needed to analyse copious amounts of experimental data from cellular GRNs. To meet this need, cloud computing is promising as reported in the literature. Here we present two new algorithms for reverse engineering GRNs in a cloud environment. The algorithms, implemented in Spark, employ an information-theoretic approach to infer GRNs from time-series gene expression data. Experimental results show that one of our new algorithms is faster than, yet as accurate as, two existing cloud-based GRN inference methods.

Microarray experiments generate data sets containing valuable information on the gene expression levels of millions of genes in the form of a set of biological samples. Inference of gene regulatory networks from microarray data has become an important research area in bioinformatics. Several computational methods have been proposed to infer important relationships between transcription factors with target genes from gene expression and transcription factor data sets. The inferences from these methods are consistent with the biological literature and can help researchers design reasonable and efficient drugs to resist different diseases. This paper is a survey of different methods used for preprocessing and inferring the gene regulatory networks from a data set of gene expression.

Based on benchmarking various methods and analyzing multiple real scRNA-seq datasets, a computational platform/workflow and a set of tips for best practices are developed for analyzing causal interactions or relationships in single cells.

Inferring gene regulatory networks from temporal expression profiles under time-delay and noise

EnGRNT: Inference of gene regulatory networks using ensemble methods and topological feature extraction

To address one of the most challenging ecosystems issues at the cellular level, this paper surveys the fuzzy methods used in gene regulatory networks (GRNs) inference. GRNs represent causal relationships between genes that have a direct influence on the life and the development of living organisms, and provide a useful contribution to the understanding of the cellular functions as well as the mechanisms of diseases. The ecosystems impacted by GRN inference span various levels from cell to society -- globally.

A survey of the methodological process of modeling, inference, and evaluation of gene regulatory networks using scRNA-Seq data.

Single-cell RNA sequencing has substantially advanced our understanding of gene expression dynamics and cellular heterogeneity. In recent years, deep learning (DL) has emerged as a promising approach to infer genetic regulation. However, these methods still face challenges in representing complex regulatory mechanisms. Thus, it remains imperative to develop new algorithms to enhance both effectiveness and reliability. We propose DeepCE, a DL framework for correlation-enhanced gene regulatory network (GRN) inference. DeepCE strengthens the extraction of dynamic regulation by integrating bidirectional gated recurrent units with convolutional neural networks (CNNs). Specifically, bidirectional gated recurrent units captures dynamic temporal dependencies, while CNNs focuses on local spatial patterns within single-cell data, enabling the model to uncover complex gene-gene interactions and generate high-quality GRNs. This framework improves the accuracy and robustness of GRN inference by smoothing noisy gene expression data, extracting time-lagged regulatory signals, and filtering out spurious correlations. Experiments conducted on mouse and human datasets demonstrate the strong performance of DeepCE. Performance evaluations show that DeepCE outperforms existing methods, achieving the highest AUROC and AUPR scores. Codes for DeepCE are free available in the GitHub https://github.com/sxiaodai/DeepCE.

Biological network inference is a crucial problem to solve in Bioinformatics as most of biological process are based on bio molecular interactions. Many researchers have worked on especially the inference of gene regulatory networks where a node and edge represent a gene and regulation relationship respectively assuming that a gene can regulate another gene indirectly. However, a gene expression level can be influenced by not only genes and proteins but also other biological factors. Therefore, the inference could be more effective if those factors are considered in gene regulatory network inferences. In this paper, we propose an integrative approach to infer gene regulatory networks where a gene can be regulated by not only gene and but also DNA Methylation and copy number variation. It is assumed that a gene can be directly regulated by a single DNA Methylation and copy number variation at most. The simulation results show that our method outperforms popular and state-of-the-art methods of biological network inference. In addition, we applied the proposed method to psychiatric disorder data. The inferred networks provide the relationships within a set of genes that are more likely to be regulated by DNA Methylation and copy number variation of the genes.