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Network-assisted genetic dissection of pathogenicity and drug resistance in the opportunistic human pathogenic fungus Cryptococcus neoformans

机译:网络辅助遗传剖析机会性人类病原性真菌新隐球菌

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摘要

Cryptococcus neoformans is an opportunistic human pathogenic fungus that causes meningoencephalitis. Due to the increasing global risk of cryptococcosis and the emergence of drug-resistant strains, the development of predictive genetics platforms for the rapid identification of novel genes governing pathogenicity and drug resistance of C. neoformans is imperative. The analysis of functional genomics data and genome-scale mutant libraries may facilitate the genetic dissection of such complex phenotypes but with limited efficiency. Here, we present a genome-scale co-functional network for C. neoformans, CryptoNet, which covers ~81% of the coding genome and provides an efficient intermediary between functional genomics data and reverse-genetics resources for the genetic dissection of C. neoformans phenotypes. CryptoNet is the first genome-scale co-functional network for any fungal pathogen. CryptoNet effectively identified novel genes for pathogenicity and drug resistance using guilt-by-association and context-associated hub algorithms. CryptoNet is also the first genome-scale co-functional network for fungi in the basidiomycota phylum, as Saccharomyces cerevisiae belongs to the ascomycota phylum. CryptoNet may therefore provide insights into pathway evolution between two distinct phyla of the fungal kingdom. The CryptoNet web server (www.inetbio.org/cryptonet) is a public resource that provides an interactive environment of network-assisted predictive genetics for C. neoformans.
机译:新型隐球菌是引起脑膜脑炎的机会性人类致病真菌。由于全球隐球菌风险增加和耐药菌株的出现,迫切需要开发预测性遗传学平台,以快速鉴定控制新孢子虫的致病性和耐药性的新基因。功能基因组学数据和基因组规模的突变体文库的分析可能有助于这种复杂的表型的遗传解剖,但效率有限。在这里,我们介绍了新隐孢子虫的基因组规模协同网络CryptoNet,该网络覆盖了约81%的编码基因组,并在功能基因组学数据和反向遗传资源之间为新孢子虫的遗传分离提供了有效的中介。表型。 CryptoNet是第一个针对任何真菌病原体的基因组规模协同功能网络。 CryptoNet使用内关联和上下文关联集线器算法有效地识别了致病性和耐药性的新基因。由于酿酒酵母属于门孢菌,因此CryptoNet还是第一种在门脉菌中真菌的基因组规模的功能网络。因此,CryptoNet可以提供有关真菌界的两个不同门之间的途径进化的见解。 CryptoNet Web服务器(www.inetbio.org/cryptonet)是一种公共资源,它为新孢梭菌提供了网络辅助的预测遗传学的交互环境。

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