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- Bioinformatics in microbial biotechnology – a mini review

Despite being a young field, bioinformatics has helped both fundamental microbiology and biotechnology through the development of algorithms, tools, and discoveries refining the abstract model of microbial cell functioning. The major impact of the bioinformatics has been in automating the microbial genome sequencing, the development of integrated databases over the Internet, and analysis of genomes to understand gene and genome function. BLAST based database search and Smith-Waterman based gene-pair alignment algorithm and their variations are being used extensively in comparing genes and genomes, and have become the first steps to derive the gene-function and the functionality of genomes. Significant success has been achieved in comparative genome analysis to: (i) identify conserved function within a genome family, (ii) identify specific genes in a group of genomes, and (iii) model 3D structures of proteins and docking of biochemical compounds and receptors. These successes have direct impact in the development of anti microbial agents, vaccines, and rational drug design. By integrating the knowledge of orthologs and gene-functions, gene-grouping based upon the integration of pair-wise genome comparison, and co-transcribed gene-groups, and graph based matching of substrates and products catalyzed by enzymes metabolic pathways reconstruction has been nearly automated.

The current front has moved to the identification of regulatory pathways, identification of protein-protein interactions, protein-DNA interactions, protein-RNA interactions, and simulations of metabolic reactions to study the effect of reaction rates, and the analysis of experimental data available from micro-array data to study the correlation between the gene-expressions and stress conditions.

Most of the bioinformatics techniques are critically dependent upon the knowledge derived from wet laboratories and the available computational algorithms and tools. Unfortunately, both the resources have limited capability of handling a vast amount of data to interpret genomics and proteomics with so many unknowns. Since there is a limited set of gene-functions available from the wet lab data, there are many holes in the complete picture of gene functions in many newly sequenced genomes. A lack of integration of bioinformatics research with biochemical knowledge also contributes to the holes in the complete picture.

The mathematical modeling approaches are suitable for new discoveries to derive candidate genes for vaccine and rational drug design, metabolic pathways, metabolic pathway variations, and transcription factors for regulatory pathways. However modeling results contain many false positives and false negatives. These results need to be verified and cured by wet-lab experiments. However, complete verification is becoming humanly impossible due to the unavailability of experts, resources, and problems in co-ordination and ever changing bioinformatics databases caused by new analysis and discoveries [51].

With the availability of better cell visualization techniques and the abstract genomics models based upon current bioinformatics analysis and their integration with existing biochemical knowledge, the microbial wet lab experiments will become more focused in their goal. The progress in bioinformatics and wet-lab techniques has to remain interdependent and focused complementing each other for their own progress and for the progress of biotechnology in future. In future more and more focus would be to apply the techniques in an integrated way to manipulate the microbial cells at systemic level.

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