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      Identification of Modules With Similar Gene Regulation and Metabolic Functions Based on Co-expression Data

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          Abstract

          Biological systems respond to environmental perturbations and to a large diversity of compounds through gene interactions, and these genetic factors comprise complex networks. In particular, a wide variety of gene co-expression networks have been constructed in recent years thanks to the dramatic increase of experimental information obtained with techniques, such as microarrays and RNA sequencing. These networks allow the identification of groups of co-expressed genes that can function in the same process and, in turn, these networks may be related to biological functions of industrial, medical and academic interest. In this study, gene co-expression networks for 17 bacterial organisms from the COLOMBOS database were analyzed via weighted gene co-expression network analysis and clustered into modules of genes with similar expression patterns for each species. These networks were analyzed to determine relevant modules through a hypergeometric approach based on a set of transcription factors and enzymes for each genome. The richest modules were characterized using PFAM families and KEGG metabolic maps. Additionally, we conducted a Gene Ontology analysis for enrichment of biological functions. Finally, we identified modules that shared similarity through all the studied organisms by using comparative genomics.

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          Most cited references37

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          A gene-coexpression network for global discovery of conserved genetic modules.

          To elucidate gene function on a global scale, we identified pairs of genes that are coexpressed over 3182 DNA microarrays from humans, flies, worms, and yeast. We found 22,163 such coexpression relationships, each of which has been conserved across evolution. This conservation implies that the coexpression of these gene pairs confers a selective advantage and therefore that these genes are functionally related. Many of these relationships provide strong evidence for the involvement of new genes in core biological functions such as the cell cycle, secretion, and protein expression. We experimentally confirmed the predictions implied by some of these links and identified cell proliferation functions for several genes. By assembling these links into a gene-coexpression network, we found several components that were animal-specific as well as interrelationships between newly evolved and ancient modules.
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            Genetics of gene expression and its effect on disease.

            Common human diseases result from the interplay of many genes and environmental factors. Therefore, a more integrative biology approach is needed to unravel the complexity and causes of such diseases. To elucidate the complexity of common human diseases such as obesity, we have analysed the expression of 23,720 transcripts in large population-based blood and adipose tissue cohorts comprehensively assessed for various phenotypes, including traits related to clinical obesity. In contrast to the blood expression profiles, we observed a marked correlation between gene expression in adipose tissue and obesity-related traits. Genome-wide linkage and association mapping revealed a highly significant genetic component to gene expression traits, including a strong genetic effect of proximal (cis) signals, with 50% of the cis signals overlapping between the two tissues profiled. Here we demonstrate an extensive transcriptional network constructed from the human adipose data that exhibits significant overlap with similar network modules constructed from mouse adipose data. A core network module in humans and mice was identified that is enriched for genes involved in the inflammatory and immune response and has been found to be causally associated to obesity-related traits.
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              The regulation of bacterial transcription initiation.

              Bacteria use their genetic material with great effectiveness to make the right products in the correct amounts at the appropriate time. Studying bacterial transcription initiation in Escherichia coli has served as a model for understanding transcriptional control throughout all kingdoms of life. Every step in the pathway between gene and function is exploited to exercise this control, but for reasons of economy, it is plain that the key step to regulate is the initiation of RNA-transcript formation.
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                Author and article information

                Contributors
                Journal
                Front Mol Biosci
                Front Mol Biosci
                Front. Mol. Biosci.
                Frontiers in Molecular Biosciences
                Frontiers Media S.A.
                2296-889X
                13 December 2019
                2019
                : 6
                : 139
                Affiliations
                [1] 1Departamento de Ingeniería de Sistemas Computacionales y Automatización, Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Ciudad Universitaria, Universidad Nacional Autónoma de México , Ciudad de México, Mexico
                [2] 2Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad Nacional Autónoma de México, Unidad Académica Yucatán , Mérida, Mexico
                [3] 3Centro de Genómica y Bioinformática, Facultad de Ciencias, Universidad Mayor , Santiago, Chile
                Author notes

                Edited by: Elena Papaleo, Danish Cancer Society Research Center (DCRC), Denmark

                Reviewed by: Tao Huang, Shanghai Institutes for Biological Sciences (CAS), China; Zhen Su, China Agricultural University (CAU), China

                *Correspondence: Edgardo Galán-Vásquez edgardo.galan@ 123456iimas.unam.mx

                This article was submitted to Biological Modeling and Simulation, a section of the journal Frontiers in Molecular Biosciences

                Article
                10.3389/fmolb.2019.00139
                6929668
                31921888
                1735f4a5-5c58-4b01-8612-21e54f0211d4
                Copyright © 2019 Galán-Vásquez and Perez-Rueda.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 August 2019
                : 18 November 2019
                Page count
                Figures: 7, Tables: 1, Equations: 0, References: 51, Pages: 12, Words: 6878
                Funding
                Funded by: Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México 10.13039/501100006087
                Funded by: CYTED Ciencia y Tecnología para el Desarrollo 10.13039/501100008441
                Categories
                Molecular Biosciences
                Original Research

                transcription factors,gene expression,metabolism,gene co-expression networks,wgcna

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