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Understanding DNA methylome profile of Malawian Mycobacterium tuberculosis clinical isolates

ABSTRACT: This is raw sequence data of Mycobacterium tuberculosis Methylation profile generated using PacBio Sequencing system.

PROVIDER: PRJEB28592 | ENA |

REPOSITORIES: ENA

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Dataset's files

Source:

			Action	DRS
	ERR2788350_subreads.fastq.gz	Fastqsanger.gz
	ERR2788351_subreads.fastq.gz	Fastqsanger.gz
	ERR2788342_subreads.fastq.gz	Fastqsanger.gz
	ERR2788352_subreads.fastq.gz	Fastqsanger.gz
	ERR2788343_subreads.fastq.gz	Fastqsanger.gz

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Characterization of DNA methylation in Malawian <i>Mycobacterium tuberculosis</i> clinical isolates.

Project description:BackgroundAlthough Mycobacterium tuberculosis (Mtb) strains exhibit genomic homology of >99%, there is considerable variation in the phenotype. The underlying mechanisms of phenotypic heterogeneity in Mtb are not well understood but epigenetic variation is thought to contribute. At present the methylome of Mtb has not been completely characterized.MethodsWe completed methylomes of 18 Mycobacterium tuberculosis (Mtb) clinical isolates from Malawi representing the largest number of Mtb genomes to be completed in a single study using Single Molecule Real Time (SMRT) sequencing to date.ResultsWe replicate and confirm four methylation disrupting mutations in 4 lineages of Mtb. For the first time we report complete loss of methylation courtesy of C758T (S253L) mutation in the MamB gene of Indo-oceanic lineage of Mtb. Additionally, we report a novel missense mutation G454A (G152S) in the MamA gene of the Euro-American lineage which could potentially be attributed to total disruption of methylation in the CCCAG motif but partial loss in a partner motif. Through a genomic and methylome comparative analysis with a global sample of sixteen, we report previously unknown mutations affecting the pks15/1 locus in L6 isolates. We confirm that methylation in Mtb is lineage specific although some unresolved issues still remain.

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Mycobacterium tuberculosis Complex Clinical Isolates exhibit unique gene expression profiles in vitro and inside macrophages

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