An integrated whole genome analysis of Mycobacterium tuberculosis reveals insights into relationship between its genome, transcriptome and methylome

Abstract Human tuberculosis disease (TB), caused by Mycobacterium tuberculosis (Mtb), is a complex disease, with a spectrum of outcomes. Genomic, transcriptomic and methylation studies have revealed differences between Mtb lineages, likely to impact on transmission, virulence and drug resistance. Ho...

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Autores principales:	Paula J. Gomez-Gonzalez, Nuria Andreu, Jody E. Phelan, Paola Florez de Sessions, Judith R. Glynn, Amelia C. Crampin, Susana Campino, Philip D. Butcher, Martin L. Hibberd, Taane G. Clark
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/81df4f864ec84de0b601906353fb8804
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spelling	oai:doaj.org-article:81df4f864ec84de0b601906353fb88042021-12-02T15:09:49ZAn integrated whole genome analysis of Mycobacterium tuberculosis reveals insights into relationship between its genome, transcriptome and methylome10.1038/s41598-019-41692-22045-2322https://doaj.org/article/81df4f864ec84de0b601906353fb88042019-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-41692-2https://doaj.org/toc/2045-2322Abstract Human tuberculosis disease (TB), caused by Mycobacterium tuberculosis (Mtb), is a complex disease, with a spectrum of outcomes. Genomic, transcriptomic and methylation studies have revealed differences between Mtb lineages, likely to impact on transmission, virulence and drug resistance. However, so far no studies have integrated sequence-based genomic, transcriptomic and methylation characterisation across a common set of samples, which is critical to understand how DNA sequence and methylation affect RNA expression and, ultimately, Mtb pathogenesis. Here we perform such an integrated analysis across 22 M. tuberculosis clinical isolates, representing ancient (lineage 1) and modern (lineages 2 and 4) strains. The results confirm the presence of lineage-specific differential gene expression, linked to specific SNP-based expression quantitative trait loci: with 10 eQTLs involving SNPs in promoter regions or transcriptional start sites; and 12 involving potential functional impairment of transcriptional regulators. Methylation status was also found to have a role in transcription, with evidence of differential expression in 50 genes across lineage 4 samples. Lack of methylation was associated with three novel variants in mamA, likely to cause loss of function of this enzyme. Overall, our work shows the relationship of DNA sequence and methylation to RNA expression, and differences between ancient and modern lineages. Further studies are needed to verify the functional consequences of the identified mechanisms of gene expression regulation.Paula J. Gomez-GonzalezNuria AndreuJody E. PhelanPaola Florez de SessionsJudith R. GlynnAmelia C. CrampinSusana CampinoPhilip D. ButcherMartin L. HibberdTaane G. ClarkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Paula J. Gomez-Gonzalez Nuria Andreu Jody E. Phelan Paola Florez de Sessions Judith R. Glynn Amelia C. Crampin Susana Campino Philip D. Butcher Martin L. Hibberd Taane G. Clark An integrated whole genome analysis of Mycobacterium tuberculosis reveals insights into relationship between its genome, transcriptome and methylome
description	Abstract Human tuberculosis disease (TB), caused by Mycobacterium tuberculosis (Mtb), is a complex disease, with a spectrum of outcomes. Genomic, transcriptomic and methylation studies have revealed differences between Mtb lineages, likely to impact on transmission, virulence and drug resistance. However, so far no studies have integrated sequence-based genomic, transcriptomic and methylation characterisation across a common set of samples, which is critical to understand how DNA sequence and methylation affect RNA expression and, ultimately, Mtb pathogenesis. Here we perform such an integrated analysis across 22 M. tuberculosis clinical isolates, representing ancient (lineage 1) and modern (lineages 2 and 4) strains. The results confirm the presence of lineage-specific differential gene expression, linked to specific SNP-based expression quantitative trait loci: with 10 eQTLs involving SNPs in promoter regions or transcriptional start sites; and 12 involving potential functional impairment of transcriptional regulators. Methylation status was also found to have a role in transcription, with evidence of differential expression in 50 genes across lineage 4 samples. Lack of methylation was associated with three novel variants in mamA, likely to cause loss of function of this enzyme. Overall, our work shows the relationship of DNA sequence and methylation to RNA expression, and differences between ancient and modern lineages. Further studies are needed to verify the functional consequences of the identified mechanisms of gene expression regulation.
format	article
author	Paula J. Gomez-Gonzalez Nuria Andreu Jody E. Phelan Paola Florez de Sessions Judith R. Glynn Amelia C. Crampin Susana Campino Philip D. Butcher Martin L. Hibberd Taane G. Clark
author_facet	Paula J. Gomez-Gonzalez Nuria Andreu Jody E. Phelan Paola Florez de Sessions Judith R. Glynn Amelia C. Crampin Susana Campino Philip D. Butcher Martin L. Hibberd Taane G. Clark
author_sort	Paula J. Gomez-Gonzalez
title	An integrated whole genome analysis of Mycobacterium tuberculosis reveals insights into relationship between its genome, transcriptome and methylome
title_short	An integrated whole genome analysis of Mycobacterium tuberculosis reveals insights into relationship between its genome, transcriptome and methylome
title_full	An integrated whole genome analysis of Mycobacterium tuberculosis reveals insights into relationship between its genome, transcriptome and methylome
title_fullStr	An integrated whole genome analysis of Mycobacterium tuberculosis reveals insights into relationship between its genome, transcriptome and methylome
title_full_unstemmed	An integrated whole genome analysis of Mycobacterium tuberculosis reveals insights into relationship between its genome, transcriptome and methylome
title_sort	integrated whole genome analysis of mycobacterium tuberculosis reveals insights into relationship between its genome, transcriptome and methylome
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/81df4f864ec84de0b601906353fb8804
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An integrated whole genome analysis of Mycobacterium tuberculosis reveals insights into relationship between its genome, transcriptome and methylome

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