Genome-Wide Comparative Analysis of Aspergillus fumigatus Strains: The Reference Genome as a Matter of Concern
Genome-Wide Comparative Analysis of Aspergillus fumigatus Strains: The Reference Genome as a Matter of Concern
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DOI：
10.3390/genes9070363
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发表时间：
2018-07-01
期刊：
影响因子：
3.5
通讯作者：
Mellado, Emilia
中科院分区：
文献类型：
--
作者：
Garcia-Rubio, Rocio;Monzon, Sara;Mellado, Emilia
烟曲霉是一种普遍存在的致病霉菌，也是免疫功能低下患者的主要病原体。三唑类化合物的效果，A。烟曲霉第一线治疗，正受到迅速和全球出现的唑类耐药性的威胁。全基因组测序（WGS）已成为分析A.烟曲霉菌株，其遗传背景和抗真菌药物耐药性的发展。虽然WGS分析可以提供大量有价值的新信息，但仍存在一些应考虑的局限性。基于全基因组比较数据和单核苷酸变异（SNV）识别的这些分析取决于测序、组装的质量、变异识别标准以及参考基因组的适当选择，参考基因组必须在遗传上接近分析中包括的基因组。在本研究中，28 A.对内部测序的烟曲霉基因组和公共数据库中的73个基因组进行了分析。所有基因组分布在四个簇中，并且根据用作参考的基因组（Af293或A1163）显示可变数目的SNV。每个参考基因组属于不同的簇。结果表明，选择最合适的A。烟曲霉参考基因组，以避免误导性的结论。
Aspergillus fumigatus is a ubiquitous saprophytic mold and a major pathogen in immunocompromised patients. The effectiveness of triazole compounds, the A. fumigatus first line treatment, is being threatened by a rapid and global emergence of azole resistance. Whole genome sequencing (WGS) has emerged as an invaluable tool for the analysis of genetic differences between A. fumigatus strains, their genetic background, and antifungal resistance development. Although WGS analyses can provide a valuable amount of novel information, there are some limitations that should be considered. These analyses, based on genome-wide comparative data and single nucleotide variant (SNV) calling, are dependent on the quality of sequencing, assembling, the variant calling criteria, as well as on the suitable selection of the reference genome, which must be genetically close to the genomes included in the analysis. In this study, 28 A. fumigatus genomes sequenced in-house and 73 available in public data bases have been analyzed. All genomes were distributed in four clusters and showed a variable number of SNVs depending on the genome used as reference (Af293 or A1163). Each reference genome belonged to a different cluster. The results highlighted the importance of choosing the most suitable A. fumigatus reference genome to avoid misleading conclusions.