The human commensal and opportunistic fungal pathogen Candida albicans displays extensive genetic and phenotypic variation across clinical isolates. Here, we performed RNA sequencing on 21 well-characterized isolates to examine how genetic variation contributes to gene expression differences, and to link these differences to phenotypic traits. C. albicans adapts primarily through clonal evolution and yet hierarchical clustering of gene expression profiles in this set of isolates did not reproduce their phylogenetic relationship. Strikingly, strain-specific gene expression was prevalent in some strain backgrounds. Association of gene expression with phenotypic data by differential analysis, linear correlation, and assembly of gene networks connected both previously characterized and novel genes with 23 C. albicans traits. Construction of de novo gene modules produced a gene atlas incorporating 67% of C. albicans genes and revealed correlations between expression modules and important phenotypes such as systemic virulence. Furthermore, targeted investigation of two modules that have novel roles in growth and filamentation supported our bioinformatic predictions. Together, these studies reveal widespread transcriptional variation across C. albicans isolates and identify genetic and epigenetic links to phenotypic variation based on co-expression network analysis.

中文翻译：

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种内转录分析揭示了白色念珠菌致病性状的关键调控因子

人类共生和机会性真菌病原体白色念珠菌在临床分离株之间表现出广泛的遗传和表型变异。在这里，我们对21个特征明确的分离株进行了RNA测序，以检验遗传变异如何导致基因表达差异，并将这些差异与表型性状联系起来。白色念珠菌主要通过克隆进化来适应，但是在这组分离物中，基因表达谱的分级聚类并没有再现它们的系统发生关系。令人惊讶的是，在某些菌株背景中普遍存在菌株特异性基因表达。通过差异分析，线性相关和基因网络的组装，将基因表达与表型数据相关联，将先前表征的基因和新基因与23 C.白色念珠菌性状联系起来。从头构建基因模块产生了包含67％白色念珠菌基因的基因图谱，并揭示了表达模块与重要表型（如系统毒力）之间的相关性。此外，针对在生长和丝化中具有新作用的两个模块的针对性研究支持了我们的生物信息学预测。总之，这些研究揭示了在白色念珠菌分离物中广泛的转录变异，并基于共表达网络分析确定了与表型变异的遗传和表观遗传联系。对在生长和丝化中具有新作用的两个模块的有针对性的研究支持了我们的生物信息学预测。总之，这些研究揭示了在白色念珠菌分离物中广泛的转录变异，并基于共表达网络分析确定了与表型变异的遗传和表观遗传联系。对在生长和丝化中具有新作用的两个模块的有针对性的研究支持了我们的生物信息学预测。总之，这些研究揭示了在白色念珠菌分离物中广泛的转录变异，并基于共表达网络分析确定了与表型变异的遗传和表观遗传联系。