Rathi Bhawna, Sarangi Aditya N, Trivedi Nidhi
Biomedical Informatics Centre, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.
Bioinformation. 2009 Oct 11;4(4):143-50. doi: 10.6026/97320630004143.
Large genomic sequencing projects of pathogens as well as human genome leads to immense genomic and proteomic data which would be very beneficial for the novel target identification in pathogens. Subtractive genomic approach is one of the most useful strategies helpful in identification of potential targets. The approach works by subtracting the genes or proteins homologous to both host and the pathogen and identify those set of gene or proteins which are essential for the pathogen and are exclusively present in the pathogen. Subtractive genomic approach is employed to identify novel target in salmonella typhi. The pathogen has 4718 proteins out of which 300 are found to be essential (" indispensable to support cellular life") in the pathogen with no human homolog. Metabolic pathway analyses of these 300 essential proteins revealed that 149 proteins are exclusively involved in several metabolic pathway of S. typhi. 8 metabolic pathways are found to be present exclusively in the pathogen comprising of 27 enzymes unique to the pathogen. Thus, these 27 proteins may serve as prospective drug targets. Sub-cellular localization prediction of the 300 essential proteins was done which reveals that 11 proteins lie on the outer membrane of the pathogen which could be probable vaccine candidates.
病原体以及人类基因组的大型基因组测序项目产生了海量的基因组和蛋白质组数据,这对于在病原体中鉴定新靶点非常有益。消减基因组方法是有助于鉴定潜在靶点的最有用策略之一。该方法通过减去宿主和病原体共有的基因或蛋白质,来识别那些对病原体至关重要且仅存在于病原体中的基因或蛋白质组。消减基因组方法被用于在伤寒沙门氏菌中鉴定新靶点。该病原体有4718种蛋白质,其中300种被发现对病原体是必不可少的(“对维持细胞生命不可或缺”)且无人类同源物。对这300种必需蛋白质的代谢途径分析表明,149种蛋白质专门参与伤寒沙门氏菌的几种代谢途径。发现有8种代谢途径仅存在于该病原体中,由该病原体特有的27种酶组成。因此,这27种蛋白质可能作为潜在的药物靶点。对这300种必需蛋白质进行了亚细胞定位预测,结果显示有11种蛋白质位于病原体的外膜上,可能是候选疫苗。