Divergences in gene repertoire among the reference Prevotella genomes derived from distinct body sites of human.

BACKGROUND: The community composition of the human microbiome is known to vary at distinct anatomical niches. But little is known about the nature of variations, if any, at the genome/sub-genome levels of a specific microbial community across different niches. The present report aims to explore, as a case study, the variations in gene repertoire of 28 Prevotella reference genomes derived from different body-sites of human, as reported earlier by the Human Microbiome Consortium. RESULTS: The pan-genome for Prevotella remains "open". On an average, 17% of predicted protein-coding genes of any particular Prevotella genome represent the conserved core genes, while the remaining 83% contribute to the flexible and singletons. The study reveals exclusive presence of 11798, 3673, 3348 and 934 gene families and exclusive absence of 17, 221, 115 and 645 gene families in Prevotella genomes derived from human oral cavity, gastro-intestinal tracts (GIT), urogenital tract (UGT) and skin, respectively. Distribution of various functional COG categories differs significantly among the habitat-specific genes. No niche-specific variations could be observed in distribution of KEGG pathways. CONCLUSIONS: Prevotella genomes derived from different body sites differ appreciably in gene repertoire, suggesting that these microbiome components might have developed distinct genetic strategies for niche adaptation within the host. Each individual microbe might also have a component of its own genetic machinery for host adaptation, as appeared from the huge number of singletons.

Association of purine asymmetry, strand-biased gene distribution and PolC within Firmicutes and beyond: a new appraisal.

BACKGROUND: The Firmicutes often possess three conspicuous genome features: marked Purine Asymmetry (PAS) across two strands of replication, Strand-biased Gene Distribution (SGD) and presence of two isoforms of DNA polymerase III alpha subunit, PolC and DnaE. Despite considerable research efforts, it is not clear whether the co-existence of PAS, PolC and/or SGD is an essential and exclusive characteristic of the Firmicutes. The nature of correlations, if any, between these three features within and beyond the lineages of Firmicutes has also remained elusive. The present study has been designed to address these issues. RESULTS: A large-scale analysis of diverse bacterial genomes indicates that PAS, PolC and SGD are neither essential nor exclusive features of the Firmicutes. PolC prevails in four bacterial phyla: Firmicutes, Fusobacteria, Tenericutes and Thermotogae, while PAS occurs only in subsets of Firmicutes, Fusobacteria and Tenericutes. There are five major compositional trends in Firmicutes: (I) an explicit PAS or G + A-dominance along the entire leading strand (II) only G-dominance in the leading strand, (III) alternate stretches of purine-rich and pyrimidine-rich sequences, (IV) G + T dominance along the leading strand, and (V) no identifiable patterns in base usage. Presence of strong SGD has been observed not only in genomes having PAS, but also in genomes with G-dominance along their leading strands - an observation that defies the notion of co-occurrence of PAS and SGD in Firmicutes. The PolC-containing non-Firmicutes organisms often have alternate stretches of R-dominant and Y-dominant sequences along their genomes and most of them show relatively weak, but significant SGD. Firmicutes having G + A-dominance or G-dominance along LeS usually show distinct base usage patterns in three codon sites of genes. Probable molecular mechanisms that might have incurred such usage patterns have been proposed. CONCLUSION: Co-occurrence of PAS, strong SGD and PolC should not be regarded as a genome signature of the Firmicutes. Presence of PAS in a species may warrant PolC and strong SGD, but PolC and/or SGD not necessarily implies PAS.

Indian genetic disease database.

Indians, representing about one-sixth of the world population, consist of several thousands of endogamous groups with strong potential for excess of recessive diseases. However, no database is available on Indian population with comprehensive information on the diseases common in the country. To address this issue, we present Indian Genetic Disease Database (IGDD) release 1.0 (http://www.igdd.iicb.res.in)--an integrated and curated repository of growing number of mutation data on common genetic diseases afflicting the Indian populations. Currently the database covers 52 diseases with information on 5760 individuals carrying the mutant alleles of causal genes. Information on locus heterogeneity, type of mutation, clinical and biochemical data, geographical location and common mutations are furnished based on published literature. The database is currently designed to work best with Internet Explorer 8 (optimal resolution 1440 × 900) and it can be searched based on disease of interest, causal gene, type of mutation and geographical location of the patients or carriers. Provisions have been made for deposition of new data and logistics for regular updation of the database. The IGDD web portal, planned to be made freely available, contains user-friendly interfaces and is expected to be highly useful to the geneticists, clinicians, biologists and patient support groups of various genetic diseases.

A pursuit of lineage-specific and niche-specific proteome features in the world of archaea.

BACKGROUND: Archaea evoke interest among researchers for two enigmatic characteristics -a combination of bacterial and eukaryotic components in their molecular architectures and an enormous diversity in their life-style and metabolic capabilities. Despite considerable research efforts, lineage- specific/niche-specific molecular features of the whole archaeal world are yet to be fully unveiled. The study offers the first large-scale in silico proteome analysis of all archaeal species of known genome sequences with a special emphasis on methanogenic and sulphur-metabolising archaea. RESULTS: Overall amino acid usage in archaea is dominated by GC-bias. But the environmental factors like oxygen requirement or thermal adaptation seem to play important roles in selection of residues with no GC-bias at the codon level. All methanogens, irrespective of their thermal/salt adaptation, show higher usage of Cys and have relatively acidic proteomes, while the proteomes of sulphur-metabolisers have higher aromaticity and more positive charges. Despite of exhibiting thermophilic life-style, korarchaeota possesses an acidic proteome. Among the distinct trends prevailing in COGs (Cluster of Orthologous Groups of proteins) distribution profiles, crenarchaeal organisms display higher intra-order variations in COGs repertoire, especially in the metabolic ones, as compared to euryarchaea. All methanogens are characterised by a presence of 22 exclusive COGs. CONCLUSIONS: Divergences in amino acid usage, aromaticity/charge profiles and COG repertoire among methanogens and sulphur-metabolisers, aerobic and anaerobic archaea or korarchaeota and nanoarchaeota, as elucidated in the present study, point towards the presence of distinct molecular strategies for niche specialization in the archaeal world.

Interplay of Various Evolutionary Modes in Genome Diversification and Adaptive Evolution of the Family Sulfolobaceae.

Sulfolobaceae family, comprising diverse thermoacidophilic and aerobic sulfur-metabolizing Archaea from various geographical locations, offers an ideal opportunity to infer the evolutionary dynamics across the members of this family. Comparative pan-genomics coupled with evolutionary analyses has revealed asymmetric genome evolution within the Sulfolobaceae family. The trend of genome streamlining followed by periods of differential gene gains resulted in an overall genome expansion in some species of this family, whereas there was reduction in others. Among the core genes, both Sulfolobus islandicus and Saccharolobus solfataricus showed a considerable fraction of positively selected genes and also higher frequencies of gene acquisition. In contrast, Sulfolobus acidocaldarius genomes experienced substantial amount of gene loss and strong purifying selection as manifested by relatively lower genome size and higher genome conservation. Central carbohydrate metabolism and sulfur metabolism coevolved with the genome diversification pattern of this archaeal family. The autotrophic CO2 fixation with three significant positively selected enzymes from S. islandicus and S. solfataricus was found to be more imperative than heterotrophic CO2 fixation for Sulfolobaceae. Overall, our analysis provides an insight into the interplay of various genomic adaptation strategies including gene gain-loss, mutation, and selection influencing genome diversification of Sulfolobaceae at various taxonomic levels and geographical locations.

Distinct, ecotype-specific genome and proteome signatures in the marine cyanobacteria Prochlorococcus.

BACKGROUND: The marine cyanobacterium Prochlorococcus marinus, having multiple ecotypes of distinct genotypic/phenotypic traits and being the first documented example of genome shrinkage in free-living organisms, offers an ideal system for studying niche-driven molecular micro-diversity in closely related microbes. The present study, through an extensive comparative analysis of various genomic/proteomic features of 6 high light (HL) and 6 low light (LL) adapted strains, makes an attempt to identify molecular determinants associated with their vertical niche partitioning. RESULTS: Pronounced strand-specific asymmetry in synonymous codon usage is observed exclusively in LL strains. Distinct dinucleotide abundance profiles are exhibited by 2 LL strains with larger genomes and G+C-content approximately 50% (group LLa), 4 LL strains having reduced genomes and G+C-content approximately 35-37% (group LLb), and 6 HL strains. Taking into account the emergence of LLa, LLb and HL strains (based on 16S rRNA phylogeny), a gradual increase in average aromaticity, pI values and beta- & coil-forming propensities and a decrease in mean hydrophobicity, instability indices and helix-forming propensities of core proteins are observed. Greater variations in orthologous gene repertoire are found between LLa and LLb strains, while higher number of positively selected genes exist between LL and HL strains. CONCLUSION: Strains of different Prochlorococcus groups are characterized by distinct compositional, physicochemical and structural traits that are not mere remnants of a continuous genetic drift, but are potential outcomes of a grand scheme of niche-oriented stepwise diversification, that might have driven them chronologically towards greater stability/fidelity and invoked upon them a special ability to inhabit diverse oceanic environments.

PanGFR-HM: A Dynamic Web Resource for Pan-Genomic and Functional Profiling of Human Microbiome With Comparative Features.

The conglomerate of microorganisms inhabiting various body-sites of human, known as the human microbiome, is one of the key determinants of human health and disease. Comprehensive pan-genomic and functional analysis approach for human microbiome components can enrich our understanding about impact of microbiome on human health. By utilizing this approach we developed PanGFR-HM (http://www.bioinfo.iicb.res.in/pangfr-hm/) - a novel dynamic web-resource that integrates genomic and functional characteristics of 1293 complete microbial genomes available from Human Microbiome Project. The resource allows users to explore genomic/functional diversity and genome-based phylogenetic relationships between human associated microbial genomes, not provided by any other resource. The key features implemented here include pan-genome and functional analysis of organisms based on taxonomy or body-site, and comparative analysis between groups of organisms. The first feature can also identify probable gene-loss events and significantly over/under represented KEGG/COG categories within pan-genome. The unique second feature can perform comparative genomic, functional and pathways analysis between 4 groups of microbes. The dynamic nature of this resource enables users to define parameters for orthologous clustering and to select any set of organisms for analysis. As an application for comparative feature of PanGFR-HM, we performed a comparative analysis with 67 Lactobacillus genomes isolated from human gut, oral cavity and urogenital tract, and therefore characterized the body-site specific genes, enzymes and pathways. Altogether, PanGFR-HM, being unique in its content and functionality, is expected to provide a platform for microbiome-based comparative functional and evolutionary genomics.

Reverse polarization in amino acid and nucleotide substitution patterns between human-mouse orthologs of two compositional extrema.

Genome-wide analysis of sequence divergence patterns in 12,024 human-mouse orthologous pairs reveals, for the first time, that the trends in nucleotide and amino acid substitutions in orthologs of high and low GC composition are highly asymmetric and polarized to opposite directions. The entire dataset has been divided into three groups on the basis of the GC content at third codon sites of human genes: high, medium, and low. High-GC orthologs exhibit significant bias in favor of the replacements, Thr --> Ala, Ser --> Ala, Val --> Ala, Lys --> Arg, Asn --> Ser, Ile --> Val etc., from mouse to human, whereas in low-GC orthologs, the reverse trends prevail. In general, in the high-GC group, residues encoded by A/U-rich codons of mouse proteins tend to be replaced by the residues encoded by relatively G/C-rich codons in their human orthologs, whereas the opposite trend is observed among the low-GC orthologous pairs. The medium-GC group shares some trends with high-GC group and some with low-GC group. The only significant trend common in all groups of orthologs, irrespective of their GC bias, is (Asp)(Mouse) --> (Glu)(Human) replacement. At the nucleotide level, high-GC orthologs have undergone a large excess of (A/T)(Mouse) --> (G/C)(Human) substitutions over (G/C)(Mouse) --> (A/T)(Human) at each codon position, whereas for low-GC orthologs, the reverse is true.

Comparative codon and amino acid composition analysis of Tritryps-conspicuous features of Leishmania major.

Comparative analyses of codon/amino acid usage in Leishmania major, Trypanosoma brucei and Trypanosoma cruzi reveal that gene expressivity and GC-bias play key roles in shaping the gene composition of all three parasites, and protein composition of L. major only. In T. brucei and T. cruzi, the major contributors to the variation in protein composition are hydropathy and/or aromaticity. Principle of Cost Minimization is followed by T. brucei, disregarded by T. cruzi and opposed by L. major. Slowly evolving highly expressed gene-products of L. major bear signatures of relatively AT-rich ancestor, while faster evolution under GC-bias has characterized the lowly expressed genes of the species by higher GC12-content.

Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity.

One of the fundamental issues in the microbiome research is characterization of the healthy human microbiota. Recent studies have elucidated substantial divergences in the microbiome structure between healthy individuals from different race and ethnicity. This review provides a comprehensive account of such geography, ethnicity or life-style-specific variations in healthy microbiome at five major body habitats-Gut, Oral-cavity, Respiratory Tract, Skin, and Urogenital Tract (UGT). The review focuses on the general trend in the human microbiome evolution-a gradual transition in the gross compositional structure along with a continual decrease in diversity of the microbiome, especially of the gut microbiome, as the human populations passed through three stages of subsistence like foraging, rural farming and industrialized urban western life. In general, gut microbiome of the hunter-gatherer populations is highly abundant with Prevotella, Proteobacteria, Spirochaetes, Clostridiales, Ruminobacter etc., while those of the urban communities are often enriched in Bacteroides, Bifidobacterium, and Firmicutes. The oral and skin microbiome are the next most diverse among different populations, while respiratory tract and UGT microbiome show lesser variations. Higher microbiome diversity is observed for oral-cavity in hunter-gatherer group with higher prevalence of Haemophilus than agricultural group. In case of skin microbiome, rural and urban Chinese populations show variation in abundance of Trabulsiella and Propionibacterium. On the basis of published data, we have characterized the core microbiota-the set of genera commonly found in all populations, irrespective of their geographic locations, ethnicity or mode of subsistence. We have also identified the major factors responsible for geography-based alterations in microbiota; though it is not yet clear which factor plays a dominant role in shaping the microbiome-nature or nurture, host genetics or his environment. Some of the geographical/racial variations in microbiome structure have been attributed to differences in host genetics and innate/adaptive immunity, while in many other cases, cultural/behavioral features like diet, hygiene, parasitic load, environmental exposure etc. overshadow genetics. The ethnicity or population-specific variations in human microbiome composition, as reviewed in this report, question the universality of the microbiome-based therapeutic strategies and recommend for geographically tailored community-scale approaches to microbiome engineering.

Analysis of Nanoarchaeum equitans genome and proteome composition: indications for hyperthermophilic and parasitic adaptation.

BACKGROUND: Nanoarchaeum equitans, the only known hyperthermophilic archaeon exhibiting parasitic life style, has raised some new questions about the evolution of the Archaea and provided a model of choice to study the genome landmarks correlated with thermo-parasitic adaptation. In this context, we have analyzed the genome and proteome composition of N. equitans and compared the same with those of other mesophiles, hyperthermophiles and obligatory host-associated organisms. RESULTS: Analysis of nucleotide, codon and amino acid usage patterns in N. equitans indicates the presence of distinct selective constraints, probably due to its adaptation to a thermo-parasitic life-style. Among the conspicuous characteristics featuring its hyperthermophilic adaptation are overrepresentation of purine bases in protein coding sequences, higher GC-content in tRNA/rRNA sequences, distinct synonymous codon usage, enhanced usage of aromatic and positively charged residues, and decreased frequencies of polar uncharged residues, as compared to those in mesophilic organisms. Positively charged amino acid residues are relatively abundant in the encoded gene-products of N. equitans and other hyperthermophiles, which is reflected in their isoelectric point distribution. Pairwise comparison of 105 orthologous protein sequences shows a strong bias towards replacement of uncharged polar residues of mesophilic proteins by Lys/Arg, Tyr and some hydrophobic residues in their Nanoarchaeal orthologs. The traits potentially attributable to the symbiotic/parasitic life-style of the organism include the presence of apparently weak translational selection in synonymous codon usage and a marked heterogeneity in membrane-associated proteins, which may be important for N. equitans to interact with the host and hence, may help the organism to adapt to the strictly host-associated life style. Despite being strictly host-dependent, N. equitans follows cost minimization hypothesis. CONCLUSION: The present study reveals that the genome and proteome composition of N. equitans are marked with the signatures of dual adaptation--one to high temperature and the other to obligatory parasitism. While the analysis of nucleotide/amino acid preferences in N. equitans offers an insight into the molecular strategies taken by the archaeon for thermo-parasitic adaptation, the comparative study of the compositional characteristics of mesophiles, hyperthermophiles and obligatory host-associated organisms demonstrates the generality of such strategies in the microbial world.

Synonymous codon usage in adenoviruses: influence of mutation, selection and protein hydropathy.

Trends in synonymous codon usage in adenoviruses have been examined through the multivariate statistical analysis on the annotated protein-coding regions of 22 adenoviral species, for which complete genome sequences are available. One of the major determinants of such trends is the G+C content at third codon positions of the genes, the average value of which varied from one viral genome to other depending on the overall mutational bias of the species. G3S and C3S interacted synergistically along the first principal axis of correspondence analysis on the Relative Synonymous Codon Usage of adenoviral genes, but antagonistically along the second principal axis. The intra-genomic variation in codon usage pattern in adenoviruses is generally influenced by asymmetrical mutational bias in two DNA strands. Other major determinants of the trends are the natural selection, putatively operative at the level of translation and quite interestingly, hydropathy of the encoded proteins. The trends in codon usage, though characterized by distinct virus-specific mutational bias, do not exhibit any sign of host-specificity. Significant variations are observed in synonymous codon choice in structural and nonstructural genes of adenoviruses.

BPGA- an ultra-fast pan-genome analysis pipeline.

Recent advances in ultra-high-throughput sequencing technology and metagenomics have led to a paradigm shift in microbial genomics from few genome comparisons to large-scale pan-genome studies at different scales of phylogenetic resolution. Pan-genome studies provide a framework for estimating the genomic diversity of the dataset, determining core (conserved), accessory (dispensable) and unique (strain-specific) gene pool of a species, tracing horizontal gene-flux across strains and providing insight into species evolution. The existing pan genome software tools suffer from various limitations like limited datasets, difficult installation/requirements, inadequate functional features etc. Here we present an ultra-fast computational pipeline BPGA (Bacterial Pan Genome Analysis tool) with seven functional modules. In addition to the routine pan genome analyses, BPGA introduces a number of novel features for downstream analyses like core/pan/MLST (Multi Locus Sequence Typing) phylogeny, exclusive presence/absence of genes in specific strains, subset analysis, atypical G + C content analysis and KEGG &COG mapping of core, accessory and unique genes. Other notable features include minimum running prerequisites, freedom to select the gene clustering method, ultra-fast execution, user friendly command line interface and high-quality graphics outputs. The performance of BPGA has been evaluated using a dataset of complete genome sequences of 28 Streptococcus pyogenes strains.

Assessment of virulence potential of uncharacterized Enterococcus faecalis strains using pan genomic approach - Identification of pathogen-specific and habitat-specific genes.

Enterococcus faecalis, a leading nosocomial pathogen and yet a prominent member of gut microbiome, lacks clear demarcation between pathogenic and non-pathogenic strains at genome level. Here we present the comparative genome analysis of 36 E. faecalis strains with different pathogenic features and from different body-habitats. This study begins by addressing the genome dynamics, which shows that the pan-genome of E. faecalis is still open, though the core genome is nearly saturated. We identified eight uncharacterized strains as potential pathogens on the basis of their co-segregation with reported pathogens in gene presence-absence matrix and Pathogenicity Island (PAI) distribution. A ~7.4 kb genomic-cassette, which is itself a part of PAI, is found to exist in all reported and potential pathogens, but not in commensals and other uncharacterized strains. This region encodes four genes and among them, products of two hypothetical genes are predicted to be intrinsically disordered that may serve as novel targets for therapeutic measures. Exclusive existence of 215, 129, 4 and 1 genes in the blood, gastrointestinal tract, urogenital tract, oral cavity and lymph node derived E. faecalis genomes respectively suggests possible employment of distinct habitat-specific genetic strategies in the adaptation of E. faecalis in human host.

Compositional variation in bacterial genes and proteins with potential expression level.

Usage of guanine and cytosine at three codon sites in eubacterial genes vary distinctly with potential expressivity, as predicted by Codon Adaptation Index (CAI). In bacteria with moderate/high GC-content, G(3) follows a biphasic relationship, while C(3) increases with CAI. In AT-rich bacteria, correlation of CAI is negative with G(3), but non-specific with C(3). Correlations of CAI with residues encoded by G-starting codons are positive, while with those by C-starting codons are usually negative/random. Average Size/Complexity Score and aromaticity of gene-products decrease with CAI, confirming general validity of cost-minimization principle in free-living eubacteria. Alcoholicity of bacterial gene-products usually decreases with expressivity.

Comparative analyses of codon and amino acid usage in symbiotic island and core genome in nitrogen-fixing symbiotic bacterium Bradyrhizobium japonicum.

Genes involved in the symbiotic interactions between the nitrogen-fixing endosymbiont Bradyrhizobium japonicum, and its leguminous host are mostly clustered in a symbiotic island (SI), acquired by the bacterium through a process of horizontal transfer. A comparative analysis of the codon and amino acid usage in core and SI genes/proteins of B. japonicum has been carried out in the present study. The mutational bias, translational selection, and gene length are found to be the major sources of variation in synonymous codon usage in the core genome as well as in SI, the strength of translational selection being higher in core genes than in SI. In core proteins, hydrophobicity is the main source of variation in amino acid usage, expressivity and aromaticity being the second and third important sources. But in SI proteins, aromaticity is the chief source of variation, followed by expressivity and hydrophobicity. In SI proteins, both the mean molecular weight and mean aromaticity of individual proteins exhibit significant positive correlation with gene expressivity, which violate the cost-minimization hypothesis. Investigation of nucleotide substitution patterns in B. japonicum and Mesorhizobium loti orthologous genes reveals that both synonymous and non-synonymous sites of highly expressed genes are more conserved than their lowly expressed counterparts and this conservation is more pronounced in the genes present in core genome than in SI.

Strand-biased gene distribution, purine assymetry and environmental factors influence protein evolution in Bacillus.

A strong purine asymmetry, along with strand-biased gene distribution and the presence of PolC, prevails in Bacillus and some other members of Firmicutes, Fusobacteria and Tenericutes. The analysis of protein features in 21 Bacillus species of diverse metabolic, virulence and ecological traits revealed that purine asymmetry in conjunction with lineage/niche specific constraints significantly influences protein evolution in Bacillus. All Bacillus species, except for Se-respiring Bacillus selenitireducens, display distinct strand-specific biases in amino acid usage, which may affect the isoelectric point or surface charge distribution of proteins with prevalence of acidic and basic residues in the leading and lagging strand proteins, respectively.

Horizontal gene transfer and bacterial diversity.

Bacterial genomes are extremely dynamic and mosaic in nature. A substantial amount of genetic information is inserted into or deleted from such genomes through the process of horizontal transfer. Through the introduction of novel physiological traits from distantly related organisms, horizontal gene transfer often causes drastic changes in the ecological and pathogenic character of bacterial species and thereby promotes microbial diversification and speciation. This review discusses how the recent influx of complete chromosomal sequences of various microorganisms has allowed for a quantitative assessment of the scope, rate and impact of horizontally transmitted information on microbial evolution.

Microbial lifestyle and genome signatures.

Microbes are known for their unique ability to adapt to varying lifestyle and environment, even to the extreme or adverse ones. The genomic architecture of a microbe may bear the signatures not only of its phylogenetic position, but also of the kind of lifestyle to which it is adapted. The present review aims to provide an account of the specific genome signatures observed in microbes acclimatized to distinct lifestyles or ecological niches. Niche-specific signatures identified at different levels of microbial genome organization like base composition, GC-skew, purine-pyrimidine ratio, dinucleotide abundance, codon bias, oligonucleotide composition etc. have been discussed. Among the specific cases highlighted in the review are the phenomena of genome shrinkage in obligatory host-restricted microbes, genome expansion in strictly intra-amoebal pathogens, strand-specific codon usage in intracellular species, acquisition of genome islands in pathogenic or symbiotic organisms, discriminatory genomic traits of marine microbes with distinct trophic strategies, and conspicuous sequence features of certain extremophiles like those adapted to high temperature or high salinity.

In silico quest for putative drug targets in Helicobacter pylori HPAG1: molecular modeling of candidate enzymes from lipopolysaccharide biosynthesis pathway.

Aimed at identification and structural characterization of novel putative therapeutic targets in H. pylori, the etiological agent of numerous gastrointestinal diseases including peptic ulcer and gastric cancer, the present study comprised of three phases. First, through subtractive analysis of metabolic pathways of Helicobacter pylori HPAG1 and human, as documented in the KEGG database, 11 pathogen-specific pathways were identified. Next, all proteins involved in these pathogen-specific pathways were scrutinized in search of promising targets and the study yielded 25 candidate target proteins that are likely to be essential for the pathogen viability, but have no homolog in human. The lipopolysaccharide (LPS) biosynthesis pathway was found to be the largest contributor (nine proteins) to this list of candidate proteins. Considering the importance of LPS in H. pylori virulence, 3D structural models of three predicted target enzymes of this pathway, namely 2-dehydro-3-deoxy-phosphooctonate aldolase, UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase and Phosphoheptose isomerase, were then built up using the homology modeling approaches. Binding site analysis and docking of the known biological substrate PEP to 2-dehydro-3-deoxyphosphooctonate aldolase revealed the potential binding pocket present in the single monomeric form of the enzyme and identified 11 amino acid residues that might play the key roles in this protein-ligand interaction.