scholarly journals Network-Based Approaches Reveal Potential Therapeutic Targets for Host-Directed Antileishmanial Therapy Driving Drug Repurposing

2021 ◽  
Author(s):  
J. Eduardo Martinez-Hernandez ◽  
Zaynab Hammoud ◽  
Alessandra Mara de Sousa ◽  
Frank Kramer ◽  
Rubens L. do Monte-Neto ◽  
...  
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Biological Process ◽  
Expression Profiles ◽  
Therapeutic Targets ◽  
Drug Repurposing ◽  
Novel Approach ◽  
Gene Regulatory ◽  
Molecular Functions ◽  
Approved Drugs

This work opens a new path to fight parasites by targeting host molecular functions by repurposing available and approved drugs. We created a novel approach to identify key proteins involved in any biological process by combining gene regulatory networks and expression profiles.

MODELING NONLINEAR GENE REGULATORY NETWORKS FROM TIME SERIES GENE EXPRESSION DATA

2008 ◽  
Vol 06 (05) ◽  
pp. 961-979 ◽  
Author(s):  
ANDRÉ FUJITA ◽  
JOÃO RICARDO SATO ◽  
HUMBERTO MIGUEL GARAY-MALPARTIDA ◽  
MARI CLEIDE SOGAYAR ◽  
CARLOS EDUARDO FERREIRA ◽  
...  
Keyword(s):  
Gene Expression ◽  
Time Series ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Expression Profiles ◽  
A Priori ◽  
Molecular Networks ◽  
Biological Knowledge ◽  
Vector Autoregressive ◽  
Gene Regulatory

In cells, molecular networks such as gene regulatory networks are the basis of biological complexity. Therefore, gene regulatory networks have become the core of research in systems biology. Understanding the processes underlying the several extracellular regulators, signal transduction, protein–protein interactions, and differential gene expression processes requires detailed molecular description of the protein and gene networks involved. To understand better these complex molecular networks and to infer new regulatory associations, we propose a statistical method based on vector autoregressive models and Granger causality to estimate nonlinear gene regulatory networks from time series microarray data. Most of the models available in the literature assume linearity in the inference of gene connections; moreover, these models do not infer directionality in these connections. Thus, a priori biological knowledge is required. However, in pathological cases, no a priori biological information is available. To overcome these problems, we present the nonlinear vector autoregressive (NVAR) model. We have applied the NVAR model to estimate nonlinear gene regulatory networks based entirely on gene expression profiles obtained from DNA microarray experiments. We show the results obtained by NVAR through several simulations and by the construction of three actual gene regulatory networks (p53, NF-κB, and c-Myc) for HeLa cells.

scholarly journals SINCERITIES: inferring gene regulatory networks from time-stamped single cell transcriptional expression profiles

2017 ◽  
Vol 34 (2) ◽  
pp. 258-266 ◽  
Author(s):  
Nan Papili Gao ◽  
S M Minhaz Ud-Dean ◽  
Olivier Gandrillon ◽  
Rudiyanto Gunawan
Keyword(s):  
Single Cell ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Expression Profiles ◽  
Transcriptional Expression ◽  
Gene Regulatory

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

2021 ◽  
Author(s):  
Hakimeh Khojasteh ◽  
Mohammad Hossein Olyaee ◽  
Alireza Khanteymoori
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Expression Profiles ◽  
Expression Data ◽  
Class Imbalance Problem ◽  
Experimental Conditions ◽  
Topological Features ◽  
Gene Regulatory

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.

scholarly journals Heat Diffusion Kernel Algorithm-Based Interpretation of the Disease Intervention Mechanism for DHA

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 754
Author(s):  
Yuan Quan ◽  
Hong-Yu Zhang ◽  
Jiang-Hui Xiong ◽  
Rui-Feng Xu ◽  
Min Gao
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Heat Diffusion ◽  
Diffusion Kernel ◽  
Significant Gene ◽  
Gene Regulatory ◽  
Core Genes ◽  
Intervention Mechanism

Docosahexaenoic acid (DHA) is effective in the prevention and treatment of cancer, congenital disorders, and various chronic diseases. According to the omnigenic hypothesis, these complex diseases are caused by disordered gene regulatory networks comprising dozens to hundreds of core genes and a mass of peripheral genes. However, conventional research on the disease intervention mechanism of DHA only focused on specific types of genes or pathways instead of examining genes at the network level, resulting in conflicting conclusions. In this study, we used HotNet2, a heat diffusion kernel algorithm, to calculate the gene regulatory networks of connectivity map (cMap)-derived agents (including DHA) based on gene expression profiles, aiming to interpret the disease intervention mechanism of DHA at the network level. As a result, significant gene regulatory networks for DHA and 676 cMap-derived agents were identified respectively. The biological functions of the DHA-regulated gene network provide preliminary insights into the mechanism by which DHA intervenes in disease. In addition, we compared the gene regulatory networks of DHA with those of cMap-derived agents, which allowed us to predict the pharmacological effects and disease intervention mechanism of DHA by analogy with similar agents with clear indications and mechanisms. Some of our analysis results were supported by experimental observations. Therefore, this study makes a significant contribution to research on the disease intervention mechanism of DHA at the regulatory network level, demonstrating the potential application value of this methodology in clarifying the mechanisms about nutrients influencing health.

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