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4.7.1 Pan-Genomics and Subtractive Genomics
Subtractive genomics – a comparative genomics approach – is currently one of the
widely used strategies throughout the last years for target prediction. Pan-genome is
another comparative genomics approach, which delineates the complete genomic
range of a given phylogenetic clade and encrypts all the possible lifestyles adopted
by its organisms (Tettelin et al. 2005, 2008). The ultimate goal of a pan-genome is
the comparison of different strains at the genomic level from the same species or
even genus. Presently, different isolates of the same pathogen and their genomic
data have unlocked the option of investigating numerous characteristics that are
fundamental to one or more species. The pan-genomic approach is one of the
options for investigating these attributes (Tettelin et al. 2005, 2008; Guimaraes et al.
2015). Tettelin et al. (2005) described the term pan-genome for the first time working with Streptococcus agalactiae, where he took eight different genomes of
Streptococcus agalactiae, a pathogenic species isolated from humans. After that,
other studies were conducted using pan-genomic analysis for different microorganisms, that includes Corynebacterium pseudotuberculosis (Soares et al. 2013),
Bacillus cereus (Rasko et al. 2005), Streptococcus pneumoniae (Donati et al. 2010),
Escherichia coli (Rasko et al. 2008), Pantoea ananatis (De Maayer et al. 2014) and
Methanobrevibacter smithii (Hansen et al. 2011). The pan-genomic studies provide
vital information about the evolution of bacteria, niche adaptation, host interaction,
and population structure as well as upshots in more applied issues like vaccine and
drug design and the identification of virulent genes (Hansen et al. 2011). The word
pan-genome refers to core genes, accessory genes, and strain specific genes. The
pan-genome includes the entire range of genes accessible to the clade studied; the
core genome contains genes shared by all strains, the accessory genome is composed of genes shared by a subset of the strains and strain specific genome refers to
the genes only present in one strain specifically (Vernikos et al. 2015). The core and
accessory genes can further be explored for the novel target’s identification against
pathogenic organisms.
Subtractive genomics is an approach applied to detect novel drug targets in
pathogenic organisms using the whole genome. This methodology involves the subtraction of sequences between the host and the pathogen proteome/ genome (proteins/genes) with the help implementation of certain rules (Fig. 4.1). This helps in
providing information for a set of proteins that are essential to the pathogen but are
not present in the host (Barh et al. 2011). There are several target identification and
prioritization databases, web tools and software are also available (Table 4.3).
According to Barh et al. 2011, an ideal target should fulfil these properties: (a) It
must be essential for survival or pathogenesis of the target organism and belongs to
the core gene of the pathogen (b) The target should belong to the pathogen’s unique
pathway. The pathway related targets are more advantageous and will be best if it is
involved in multiple pathways.
The approach of subtractive genomics for target identification has been massively applied in numerous pathogens like Treponema pallidum (Kumar Jaiswal
M. Santana et al.
4.7.1 Pan-Genomics and Subtractive Genomics
Subtractive genomics – a comparative genomics approach – is currently one of the
widely used strategies throughout the last years for target prediction. Pan-genome is
another comparative genomics approach, which delineates the complete genomic
range of a given phylogenetic clade and encrypts all the possible lifestyles adopted
by its organisms (Tettelin et al. 2005, 2008). The ultimate goal of a pan-genome is
the comparison of different strains at the genomic level from the same species or
even genus. Presently, different isolates of the same pathogen and their genomic
data have unlocked the option of investigating numerous characteristics that are
fundamental to one or more species. The pan-genomic approach is one of the
options for investigating these attributes (Tettelin et al. 2005, 2008; Guimaraes et al.
2015). Tettelin et al. (2005) described the term pan-genome for the first time working with Streptococcus agalactiae, where he took eight different genomes of
Streptococcus agalactiae, a pathogenic species isolated from humans. After that,
other studies were conducted using pan-genomic analysis for different microorganisms, that includes Corynebacterium pseudotuberculosis (Soares et al. 2013),
Bacillus cereus (Rasko et al. 2005), Streptococcus pneumoniae (Donati et al. 2010),
Escherichia coli (Rasko et al. 2008), Pantoea ananatis (De Maayer et al. 2014) and
Methanobrevibacter smithii (Hansen et al. 2011). The pan-genomic studies provide
vital information about the evolution of bacteria, niche adaptation, host interaction,
and population structure as well as upshots in more applied issues like vaccine and
drug design and the identification of virulent genes (Hansen et al. 2011). The word
pan-genome refers to core genes, accessory genes, and strain specific genes. The
pan-genome includes the entire range of genes accessible to the clade studied; the
core genome contains genes shared by all strains, the accessory genome is composed of genes shared by a subset of the strains and strain specific genome refers to
the genes only present in one strain specifically (Vernikos et al. 2015). The core and
accessory genes can further be explored for the novel target’s identification against
pathogenic organisms.
Subtractive genomics is an approach applied to detect novel drug targets in
pathogenic organisms using the whole genome. This methodology involves the subtraction of sequences between the host and the pathogen proteome/ genome (proteins/genes) with the help implementation of certain rules (Fig. 4.1). This helps in
providing information for a set of proteins that are essential to the pathogen but are
not present in the host (Barh et al. 2011). There are several target identification and
prioritization databases, web tools and software are also available (Table 4.3).
According to Barh et al. 2011, an ideal target should fulfil these properties: (a) It
must be essential for survival or pathogenesis of the target organism and belongs to
the core gene of the pathogen (b) The target should belong to the pathogen’s unique
pathway. The pathway related targets are more advantageous and will be best if it is
involved in multiple pathways.
The approach of subtractive genomics for target identification has been massively applied in numerous pathogens like Treponema pallidum (Kumar Jaiswal
M. Santana et al.