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Comparative whole-genome analysis of clinical isolates reveals characteristic architecture of Mycobacterium tuberculosis pangenome.

Periwal V, Patowary A, Vellarikkal SK, Gupta A, Singh M, Mittal A, Jeyapaul S, Chauhan RK, Singh AV, Singh PK, Garg P, Katoch VM, Katoch K, Chauhan DS, Sivasubbu S, Scaria V - PLoS ONE (2015)

Bottom Line: We identified 74 HGCs that were absent from reference strains H37Rv and H37Ra but were present in most of clinical isolates.The pangenome approach is a promising tool for studying strain specific genetic differences occurring within species.We also suggest that since selecting appropriate target genes for typing purposes requires the expected target gene be present in all isolates being typed, therefore estimating the core-component of the species becomes a subject of prime importance.

View Article: PubMed Central - PubMed

Affiliation: GN Ramachandran Knowledge Center for Genome Informatics, CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB), Mall Road, Delhi-110007, India; Academy of Scientific & Innovative Research (AcSIR), 2, Rafi Marg, Anusandhan Bhawan, New Delhi 110001, India.

ABSTRACT
The tubercle complex consists of closely related mycobacterium species which appear to be variants of a single species. Comparative genome analysis of different strains could provide useful clues and insights into the genetic diversity of the species. We integrated genome assemblies of 96 strains from Mycobacterium tuberculosis complex (MTBC), which included 8 Indian clinical isolates sequenced and assembled in this study, to understand its pangenome architecture. We predicted genes for all the 96 strains and clustered their respective CDSs into homologous gene clusters (HGCs) to reveal a hard-core, soft-core and accessory genome component of MTBC. The hard-core (HGCs shared amongst 100% of the strains) was comprised of 2,066 gene clusters whereas the soft-core (HGCs shared amongst at least 95% of the strains) comprised of 3,374 gene clusters. The change in the core and accessory genome components when observed as a function of their size revealed that MTBC has an open pangenome. We identified 74 HGCs that were absent from reference strains H37Rv and H37Ra but were present in most of clinical isolates. We report PCR validation on 9 candidate genes depicting 7 genes completely absent from H37Rv and H37Ra whereas 2 genes shared partial homology with them accounting to probable insertion and deletion events. The pangenome approach is a promising tool for studying strain specific genetic differences occurring within species. We also suggest that since selecting appropriate target genes for typing purposes requires the expected target gene be present in all isolates being typed, therefore estimating the core-component of the species becomes a subject of prime importance.

No MeSH data available.


Related in: MedlinePlus

Overlap of accessory orthologous clusters shared within each strain pair.The diagonal represent the number of clusters present in any given strain and divides the data into exactly similar halves. Color key indicates the distribution of clusters. The sharing is irrespective of the cluster being present in any other strain. The minimum number of shared clusters is 109 clusters between Mcan CIPT 140070008 and Mbovis BCG Phipps and maximum (521) is between Mbovis BCG Sweden and Mbovis BCG Prague9.
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pone.0122979.g006: Overlap of accessory orthologous clusters shared within each strain pair.The diagonal represent the number of clusters present in any given strain and divides the data into exactly similar halves. Color key indicates the distribution of clusters. The sharing is irrespective of the cluster being present in any other strain. The minimum number of shared clusters is 109 clusters between Mcan CIPT 140070008 and Mbovis BCG Phipps and maximum (521) is between Mbovis BCG Sweden and Mbovis BCG Prague9.

Mentions: An overlap of the number of accessory clusters shared within a strain pair is presented in Fig 6. The diagonal shows the total number of accessory clusters present in any strain being considered. The highest number of accessory clusters are present in the strain Mtb T17 (897) and the minimum number is present in Mbov BCG Korea (364). The upper and lower triangles are mirror images and show the number of overlapping clusters in each strain pair. The minimum number of overlapping clusters is 109 between Mcan CIPT 140070008 and Mbov BCG Phipps and maximum is 521, between Mbov BCG Sweden and Mbov BCG prague. The overlapping clusters formed a symmetrical matrix i.e. a square matrix which is equivalent to its transpose.


Comparative whole-genome analysis of clinical isolates reveals characteristic architecture of Mycobacterium tuberculosis pangenome.

Periwal V, Patowary A, Vellarikkal SK, Gupta A, Singh M, Mittal A, Jeyapaul S, Chauhan RK, Singh AV, Singh PK, Garg P, Katoch VM, Katoch K, Chauhan DS, Sivasubbu S, Scaria V - PLoS ONE (2015)

Overlap of accessory orthologous clusters shared within each strain pair.The diagonal represent the number of clusters present in any given strain and divides the data into exactly similar halves. Color key indicates the distribution of clusters. The sharing is irrespective of the cluster being present in any other strain. The minimum number of shared clusters is 109 clusters between Mcan CIPT 140070008 and Mbovis BCG Phipps and maximum (521) is between Mbovis BCG Sweden and Mbovis BCG Prague9.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390332&req=5

pone.0122979.g006: Overlap of accessory orthologous clusters shared within each strain pair.The diagonal represent the number of clusters present in any given strain and divides the data into exactly similar halves. Color key indicates the distribution of clusters. The sharing is irrespective of the cluster being present in any other strain. The minimum number of shared clusters is 109 clusters between Mcan CIPT 140070008 and Mbovis BCG Phipps and maximum (521) is between Mbovis BCG Sweden and Mbovis BCG Prague9.
Mentions: An overlap of the number of accessory clusters shared within a strain pair is presented in Fig 6. The diagonal shows the total number of accessory clusters present in any strain being considered. The highest number of accessory clusters are present in the strain Mtb T17 (897) and the minimum number is present in Mbov BCG Korea (364). The upper and lower triangles are mirror images and show the number of overlapping clusters in each strain pair. The minimum number of overlapping clusters is 109 between Mcan CIPT 140070008 and Mbov BCG Phipps and maximum is 521, between Mbov BCG Sweden and Mbov BCG prague. The overlapping clusters formed a symmetrical matrix i.e. a square matrix which is equivalent to its transpose.

Bottom Line: We identified 74 HGCs that were absent from reference strains H37Rv and H37Ra but were present in most of clinical isolates.The pangenome approach is a promising tool for studying strain specific genetic differences occurring within species.We also suggest that since selecting appropriate target genes for typing purposes requires the expected target gene be present in all isolates being typed, therefore estimating the core-component of the species becomes a subject of prime importance.

View Article: PubMed Central - PubMed

Affiliation: GN Ramachandran Knowledge Center for Genome Informatics, CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB), Mall Road, Delhi-110007, India; Academy of Scientific & Innovative Research (AcSIR), 2, Rafi Marg, Anusandhan Bhawan, New Delhi 110001, India.

ABSTRACT
The tubercle complex consists of closely related mycobacterium species which appear to be variants of a single species. Comparative genome analysis of different strains could provide useful clues and insights into the genetic diversity of the species. We integrated genome assemblies of 96 strains from Mycobacterium tuberculosis complex (MTBC), which included 8 Indian clinical isolates sequenced and assembled in this study, to understand its pangenome architecture. We predicted genes for all the 96 strains and clustered their respective CDSs into homologous gene clusters (HGCs) to reveal a hard-core, soft-core and accessory genome component of MTBC. The hard-core (HGCs shared amongst 100% of the strains) was comprised of 2,066 gene clusters whereas the soft-core (HGCs shared amongst at least 95% of the strains) comprised of 3,374 gene clusters. The change in the core and accessory genome components when observed as a function of their size revealed that MTBC has an open pangenome. We identified 74 HGCs that were absent from reference strains H37Rv and H37Ra but were present in most of clinical isolates. We report PCR validation on 9 candidate genes depicting 7 genes completely absent from H37Rv and H37Ra whereas 2 genes shared partial homology with them accounting to probable insertion and deletion events. The pangenome approach is a promising tool for studying strain specific genetic differences occurring within species. We also suggest that since selecting appropriate target genes for typing purposes requires the expected target gene be present in all isolates being typed, therefore estimating the core-component of the species becomes a subject of prime importance.

No MeSH data available.


Related in: MedlinePlus