Harnessing Whole Genome Sequencing in Medical Mycology

Abstract

Purpose of review: Comparative genome sequencing studies of human fungal pathogens enable identification of genes and variants associated with virulence and drug resistance. This review describes current approaches, resources, and advances in applying whole genome sequencing to study clinically important fungal pathogens.

Recent findings: Genomes for some important fungal pathogens were only recently assembled, revealing gene family expansions in many species and extreme gene loss in one obligate species. The scale and scope of species sequenced is rapidly expanding, leveraging technological advances to assemble and annotate genomes with higher precision. By using iteratively improved reference assemblies or those generated de novo for new species, recent studies have compared the sequence of isolates representing populations or clinical cohorts. Whole genome approaches provide the resolution necessary for comparison of closely related isolates, for example, in the analysis of outbreaks or sampled across time within a single host.

Summary: Genomic analysis of fungal pathogens has enabled both basic research and diagnostic studies. The increased scale of sequencing can be applied across populations, and new metagenomic methods allow direct analysis of complex samples.

Keywords: Fungal infections; Genome sequencing; Human fungal pathogens; Medical mycology; Review; Whole genome sequencing.

Fig. 1

Overview of whole genome sequencing approaches. a De novo assembly approach; while draft assemblies are more fragmented than finished or chromosomal assemblies, both can be annotated for gene structures and repetitive elements. b Re-sequencing approach; this approach starts with initial alignment of sequence reads to a reference assembly, with separate processes required to identify copy number variants, structural variants, and SNPs and indels