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Pan-Genome Analysis of Transcriptional Regulation in Six Salmonella enterica Serovar Typhimurium Strains Reveals Their Different Regulatory Structures
Establishing transcriptional regulatory networks (TRNs) in bacteria has been limited to well-characterized model strains. Using machine learning methods, we established the transcriptional regulatory networks of six Salmonella enterica serovar Typhimurium strains from their transcriptomes. By decomp...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9764980/ https://www.ncbi.nlm.nih.gov/pubmed/36317888 http://dx.doi.org/10.1128/msystems.00467-22 |
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author | Yuan, Yuan Seif, Yara Rychel, Kevin Yoo, Reo Chauhan, Siddharth Poudel, Saugat Al-bulushi, Tahani Palsson, Bernhard O. Sastry, Anand V. |
author_facet | Yuan, Yuan Seif, Yara Rychel, Kevin Yoo, Reo Chauhan, Siddharth Poudel, Saugat Al-bulushi, Tahani Palsson, Bernhard O. Sastry, Anand V. |
author_sort | Yuan, Yuan |
collection | PubMed |
description | Establishing transcriptional regulatory networks (TRNs) in bacteria has been limited to well-characterized model strains. Using machine learning methods, we established the transcriptional regulatory networks of six Salmonella enterica serovar Typhimurium strains from their transcriptomes. By decomposing a compendia of RNA sequencing (RNA-seq) data with independent component analysis, we obtained 400 independently modulated sets of genes, called iModulons. We (i) performed pan-genome analysis of the phylogroup structure of S. Typhimurium and analyzed the iModulons against this background, (ii) revealed different genetic signatures in pathogenicity islands that explained phenotypes, (iii) discovered three transport iModulons linked to antibiotic resistance, (iv) described concerted responses to cationic antimicrobial peptides, and (v) uncovered new regulons. Thus, by combining pan-genome and transcriptomic analytics, we revealed variations in TRNs across six strains of serovar Typhimurium. IMPORTANCE Salmonella enterica serovar Typhimurium is a pathogen involved in human nontyphoidal infections. Treating S. Typhimurium infections is difficult due to the species’s dynamic adaptation to its environment, which is dictated by a complex transcriptional regulatory network (TRN) that is different across strains. In this study, we describe the use of independent component analysis to characterize the differential TRNs across the S. Typhimurium pan-genome using a compendium of high-quality RNA-seq data. This approach provided unprecedented insights into the differences between regulation of key cellular functions and pathogenicity in the different strains. The study provides an impetus to initiate a large-scale effort to reveal the TRN differences between the major phylogroups of the pathogenic bacteria, which could fundamentally impact personalizing treatments of bacterial pathogens. |
format | Online Article Text |
id | pubmed-9764980 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-97649802022-12-21 Pan-Genome Analysis of Transcriptional Regulation in Six Salmonella enterica Serovar Typhimurium Strains Reveals Their Different Regulatory Structures Yuan, Yuan Seif, Yara Rychel, Kevin Yoo, Reo Chauhan, Siddharth Poudel, Saugat Al-bulushi, Tahani Palsson, Bernhard O. Sastry, Anand V. mSystems Research Article Establishing transcriptional regulatory networks (TRNs) in bacteria has been limited to well-characterized model strains. Using machine learning methods, we established the transcriptional regulatory networks of six Salmonella enterica serovar Typhimurium strains from their transcriptomes. By decomposing a compendia of RNA sequencing (RNA-seq) data with independent component analysis, we obtained 400 independently modulated sets of genes, called iModulons. We (i) performed pan-genome analysis of the phylogroup structure of S. Typhimurium and analyzed the iModulons against this background, (ii) revealed different genetic signatures in pathogenicity islands that explained phenotypes, (iii) discovered three transport iModulons linked to antibiotic resistance, (iv) described concerted responses to cationic antimicrobial peptides, and (v) uncovered new regulons. Thus, by combining pan-genome and transcriptomic analytics, we revealed variations in TRNs across six strains of serovar Typhimurium. IMPORTANCE Salmonella enterica serovar Typhimurium is a pathogen involved in human nontyphoidal infections. Treating S. Typhimurium infections is difficult due to the species’s dynamic adaptation to its environment, which is dictated by a complex transcriptional regulatory network (TRN) that is different across strains. In this study, we describe the use of independent component analysis to characterize the differential TRNs across the S. Typhimurium pan-genome using a compendium of high-quality RNA-seq data. This approach provided unprecedented insights into the differences between regulation of key cellular functions and pathogenicity in the different strains. The study provides an impetus to initiate a large-scale effort to reveal the TRN differences between the major phylogroups of the pathogenic bacteria, which could fundamentally impact personalizing treatments of bacterial pathogens. American Society for Microbiology 2022-11-01 /pmc/articles/PMC9764980/ /pubmed/36317888 http://dx.doi.org/10.1128/msystems.00467-22 Text en Copyright © 2022 Yuan et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Yuan, Yuan Seif, Yara Rychel, Kevin Yoo, Reo Chauhan, Siddharth Poudel, Saugat Al-bulushi, Tahani Palsson, Bernhard O. Sastry, Anand V. Pan-Genome Analysis of Transcriptional Regulation in Six Salmonella enterica Serovar Typhimurium Strains Reveals Their Different Regulatory Structures |
title | Pan-Genome Analysis of Transcriptional Regulation in Six Salmonella enterica Serovar Typhimurium Strains Reveals Their Different Regulatory Structures |
title_full | Pan-Genome Analysis of Transcriptional Regulation in Six Salmonella enterica Serovar Typhimurium Strains Reveals Their Different Regulatory Structures |
title_fullStr | Pan-Genome Analysis of Transcriptional Regulation in Six Salmonella enterica Serovar Typhimurium Strains Reveals Their Different Regulatory Structures |
title_full_unstemmed | Pan-Genome Analysis of Transcriptional Regulation in Six Salmonella enterica Serovar Typhimurium Strains Reveals Their Different Regulatory Structures |
title_short | Pan-Genome Analysis of Transcriptional Regulation in Six Salmonella enterica Serovar Typhimurium Strains Reveals Their Different Regulatory Structures |
title_sort | pan-genome analysis of transcriptional regulation in six salmonella enterica serovar typhimurium strains reveals their different regulatory structures |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9764980/ https://www.ncbi.nlm.nih.gov/pubmed/36317888 http://dx.doi.org/10.1128/msystems.00467-22 |
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