title: Comparative whole-genome analysis of clinical isolates reveals characteristic architecture of Mycobacterium tuberculosis pangenome.
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.
authors: 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.
authors: Vinita
authors: V
authors: Periwal
authors: Genomics and Molecular Medicine, CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB), Mall Road, Delhi-110007, India.
authors: Ashok
authors: A
authors: Patowary
authors: Genomics and Molecular Medicine, 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.
authors: Shamsudheen Karuthedath
authors: SK
authors: Vellarikkal
authors: Open Source Drug Discovery Unit, Council of Scientific and Industrial Research (CSIR), Anusandhan Bhavan, 2 Rafi Marg, New Delhi 110001, India.
authors: Anju
authors: A
authors: Gupta
authors: Genomics and Molecular Medicine, 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.
authors: Meghna
authors: M
authors: Singh
authors: Genomics and Molecular Medicine, CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB), Mall Road, Delhi-110007, India.
authors: Ashish
authors: A
authors: Mittal
authors: Genomics and Molecular Medicine, CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB), Mall Road, Delhi-110007, India.
authors: Shamini
authors: S
authors: Jeyapaul
authors: Genomics and Molecular Medicine, CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB), Mall Road, Delhi-110007, India.
authors: Rajendra Kumar
authors: RK
authors: Chauhan
authors: National JALMA Institute of Leprosy and other Mycobacterial Diseases, Post Box No.101,Tajganj, Agra-282001, India.
authors: Ajay Vir
authors: AV
authors: Singh
authors: National JALMA Institute of Leprosy and other Mycobacterial Diseases, Post Box No.101,Tajganj, Agra-282001, India.
authors: Pravin Kumar
authors: PK
authors: Singh
authors: National JALMA Institute of Leprosy and other Mycobacterial Diseases, Post Box No.101,Tajganj, Agra-282001, India.
authors: Parul
authors: P
authors: Garg
authors: National JALMA Institute of Leprosy and other Mycobacterial Diseases, Post Box No.101,Tajganj, Agra-282001, India.
authors: Viswa Mohan
authors: VM
authors: Katoch
authors: National JALMA Institute of Leprosy and other Mycobacterial Diseases, Post Box No.101,Tajganj, Agra-282001, India.
authors: Kiran
authors: K
authors: Katoch
authors: National JALMA Institute of Leprosy and other Mycobacterial Diseases, Post Box No.101,Tajganj, Agra-282001, India.
authors: Devendra Singh
authors: DS
authors: Chauhan
authors: Genomics and Molecular Medicine, CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB), Mall Road, Delhi-110007, India.
authors: Sridhar
authors: S
authors: Sivasubbu
authors: GN Ramachandran Knowledge Center for Genome Informatics, CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB), Mall Road, Delhi-110007, India.
authors: Vinod
authors: V
authors: Scaria
mesh_terms: D001483:Base Sequence; D055028:Comparative Genomic Hybridization; D004269:DNA, Bacterial / Q000235:genetics; D014644:Genetic Variation; D016680:Genome, Bacterial; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D010802:Phylogeny; D014376:Tuberculosis / Q000235:genetics* / Q000382:microbiology / Q000473:pathology
chemical_list: D004269:DNA, Bacterial