Abstract:The complete human genome sequences in the public database provide ways to understand the blue print of life. As of June 29, 2006, 27 archaeal, 326 bacterial and 21 eukaryotes is complete genomes are available and the sequencing for 316 bacterial, 24 archaeal, 126 eukaryotic genomes are in progress. The traditional biochemical/molecular experiments can assign accurate functions for genes in these genomes. However, the process is time-consuming and costly. Despite several efforts, only 50-60 % of genes have been annotated in most completely sequenced genomes. Automated genome sequence analysis and annotation may provide ways to understand genomes. Thus, determination of protein function is one of the challenging problems of the post-genome era. This demands bioinformatics to predict functions of un-annotated protein sequences by developing efficient tools. Here, we discuss some of the recent and popular approaches developed in Bioinformatics to predict functions for hypothetical proteins.

Abstract:The rapidly emerging field of comparative genomics has yielded dramatic results. Comparative genome analysis has become feasible with the availability of a number of completely sequenced genomes. Comparison of complete genomes between organisms allow for global views on genome evolution and the availability of many completely sequenced genomes increases the predictive power in deciphering the hidden information in genome design, function and evolution. Thus, comparison of human genes with genes from other genomes in a genomic landscape could help assign novel functions for un-annotated genes. Here, we discuss the recently used techniques for comparative genomics and their derived inferences in genome biology.Keywords: comparative genomics; genome correspondence; gene identification; genome evolution Background:As on Jan 25, 2007, 472 genomes are completely sequenced and yet another 498 are in progress. The rapid progress in genome sequencing demands more comparative analysis to gain new insights into evolutionary, biochemical, genetic, metabolic, and physiological pathways. Comparative genomics is the direct comparison of complete genetic material of one organism against that of another to gain a better understanding of how species evolved and to determine the function of genes and noncoding regions in genomes. It includes a comparison of gene number, gene content, and gene location, the length and number of coding regions (called exons) within genes, the amount of non coding DNA in each genome, and conserved regions maintained in both prokaryotic and eukaryotic groups of organisms. Comparative genomics not only can trace out the evolutionary relationship between organisms but also differences and similarities within and between species. The difference between humans and other organisms can be obtained by comparative investigations. For the purpose of documenting the distinctive features of humans, the most informative research involves comparing humans to our closest relatives, the chimpanzees and apes.

Due to accumulation of genomic data, the function of a vast amount of genes and the proteins encoded by them are unknown. Unless, the function of proteome encoded by the entire genome is not known, the biochemical processes and their importance cannot be understood. Also, the computational annotation returns a gene without any homolog in the protein database it encodes it as "hypothetical". Due to advancements in annotation projects, many genes whose evidence for expression invivo is not known and due to lack of similar protein could not be assigned function. This pose a challenge to functional genomics and automatic annotation of hypothetical genes are done at a faster rate using developed annotation tools to know the function of the hypothetical genes. Moreover, when the hypothetical genes are present in human, it is really a lacuna and hence functional annotation of the hypothetical genes in the human genome is the need of the hour. Hence, this work attempts to annotate the hypothetical genes in Human and makes the results publicly accessible using a web based database using PHP and MySQL.

Background: In our day-to-day life, we are facing many dreadful diseases caused by many infectious pathogens. These pathogens invade the living organisms (host) and lethally damaging them. These dreadful pathogens were also be used as bioweapons. Among them, Clostridium perfringens is taken for the study. Clostridium perfringens is an anaerobic, rod shaped, gram positive bacteria capable of forming spores. It is prevalent in the environment and in the intestine of humans and other animals. It is the causative agent for a wide range of diseases including food borne diseases, gas gangrene and flesh eating disease called necrotizing fasciitis. C. perfringens is commonly found on raw meat and poultry that espouse to grow in conditions with very little or no oxygen, and under ideal conditions can multiply very rapidly. These conditions are occasionally lethal due to the substantial number of toxins such as alpha toxin, beta toxin, epsilon toxin and iota toxin produced by C. perfringens. It is significantly important to analyze the Drug targets of the pathogen in order to destroy them. Objective: The present work aims in identifying potential drug targets in C. perfringens through metabolic pathway analysis. Method: Primarily, the metabolic pathways of the host and pathogen are compared to identify unique pathways in the bacteria. Among the enzymes that catalyze unique metabolic pathways, the essential ones for the survival of the pathogen are identified. The druggability of the essential enzymes are predicted through identification of its sub cellular localization and other druggable parameters. Results: The comparative metabolic pathway analysis result shows that, among the 98 metabolic pathways of C.perfringens, 25 pathways were unique that they did not have a counterpart with Human. There were 113 enzymes involved in these unique pathways. The NCBI’s protein Blast search against human was done to identify the non-homologous proteins. There were 93 non-homologous proteins. Among the 93 non-homologous proteins, 47 proteins were found to be essential. Based on their sub-cellular localization, 32 proteins were identified as potential drug targets and 15 are probable vaccine candidates. Conclusion: The present work which started with 25 different pathways with more than a hundred different enzymes, resulted in the identification of 32 putative drug targets against C.perfringens infection. All these 32 identified targets did not have any human homolog and are highly essential for the survival of the organism. They were concluded as potential drug targets. Designing of compounds to inhibit these enzymes would be successful for treating the life threatening infections caused by this pathogen.

The high-throughput genome projects have resulted in a rapid accumulation of genome sequences for a large number of organisms and large number of genes with unknown function (Hypothetical). To fully realize the value of the data, scientists need to identify proteins encoded by these genes and understand how these proteins function in making up a living cell. With experimentally verified information on protein function lagging far behind, computational methods are needed for reliable and large-scale functional annotation of proteins. Functional annotation is the process of identifying for a given gene its biological function, interaction with other elements, involvement in metabolic pathways, and any other piece of information that helps in understanding when and how a gene influences the overall system. On the other hand, many Biological Processes and Disease mechanisms are still unknown due to lack of knowledge about the function of the Hypothetical genes in Human. Once its function is revealed the so called hurdle of unknown mechanism of the Human Genome can be mastered. Hence, the present study aims to use computational approaches to annotate the function of hypothetical genes in Chromosome 2 of Human. The annotation of the hypothetical genes in human chromosoem2 was done both at the nucleotide and protein level. Among the 41 uncharacterized hypothetical genes in Human chromosome 2, the functions of 27 of them were successfully annotation. Further, experimental validation is essential to confirm the predicted function.