Institute of Bioinformatics, International Technology Park, Bangalore 560 066, India.
Clin Proteomics. 2014 Feb 3;11(1):5. doi: 10.1186/1559-0275-11-5.
Cryptococcus neoformans, a basidiomycetous fungus of universal occurrence, is a significant opportunistic human pathogen causing meningitis. Owing to an increase in the number of immunosuppressed individuals along with emergence of drug-resistant strains, C. neoformans is gaining importance as a pathogen. Although, whole genome sequencing of three varieties of C. neoformans has been completed recently, no global proteomic studies have yet been reported.
We performed a comprehensive proteomic analysis of C. neoformans var. grubii (Serotype A), which is the most virulent variety, in order to provide protein-level evidence for computationally predicted gene models and to refine the existing annotations. We confirmed the protein-coding potential of 3,674 genes from a total of 6,980 predicted protein-coding genes. We also identified 4 novel genes and corrected 104 predicted gene models. In addition, our studies led to the correction of translational start site, splice junctions and reading frame used for translation in a number of proteins. Finally, we validated a subset of our novel findings by RT-PCR and sequencing.
Proteogenomic investigation described here facilitated the validation and refinement of computationally derived gene models in the intron-rich genome of C. neoformans, an important fungal pathogen in humans.
新生隐球菌是一种普遍存在的担子菌真菌，是一种重要的机会性人类病原体，可引起脑膜炎。由于免疫抑制个体数量的增加以及耐药菌株的出现，新生隐球菌作为病原体的重要性日益增加。尽管最近已经完成了三种新生隐球菌变种的全基因组测序，但尚未有全球蛋白质组学研究的报道。
我们对最具毒力的变种新生隐球菌 var. grubii（血清型 A）进行了全面的蛋白质组学分析，为计算预测的基因模型提供了蛋白质水平的证据，并对现有注释进行了修正。我们证实了总共 6980 个预测蛋白编码基因中有 3674 个具有蛋白编码潜力。我们还鉴定了 4 个新基因，并修正了 104 个预测的基因模型。此外，我们的研究还导致了许多蛋白质中翻译起始位点、剪接接头和用于翻译的阅读框的修正。最后，我们通过 RT-PCR 和测序验证了我们的一些新发现。
本文描述的蛋白质基因组学研究促进了新生隐球菌富含内含子的基因组中计算推导基因模型的验证和修正，新生隐球菌是人类中一种重要的真菌病原体。
