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Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance

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Comparing genomic variant identification protocols for Candida auris.

Xiao Li¹, José F Muñoz¹, Lalitha Gade²

¹Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.

Microbial Genomics

|April 12, 2023

Summary

This summary is machine-generated.

This study evaluated 14 genomic variant calling pipelines for pathogenic fungi, specifically *Candida auris*. High agreement was found, but differences in read trimming and filtering impacted results, highlighting the need for standardized best practices in fungal genomics.

Keywords:

Candida benchmarking fungal genomics variant calling pipelines whole-genome sequencing

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Area of Science:

Genomics
Mycology
Bioinformatics

Background:

Genomic analyses are crucial for studying pathogenic fungi like *Candida auris*.
Current variant calling methods lack standardized controls, impacting accuracy and consistency across studies.
Global tracking of fungal outbreaks necessitates high-accuracy, reproducible genomic pipelines.

Purpose of the Study:

To evaluate 14 whole-genome variant calling pipelines for pathogenic fungi.
To compare variant calling, single-nucleotide polymorphism (SNP) counts, and phylogenetic inference.
To establish best practices for fungal pathogen genomic studies.

Main Methods:

Compared 14 independent variant calling pipelines using 35 *Candida auris* isolates from 4 clades.
Assessed pipeline performance using specificity and sensitivity metrics with chromosomal-level assemblies.
Analyzed differences attributed to read trimming, SNP calling parameters, and filtration.

Main Results:

High overall agreement of SNPs was observed across pipelines, correlated with site quality.
GATK-based pipelines showed a balanced specificity and sensitivity.
Read trimming strategies significantly impacted SAMtools-based pipelines.
Phylogenetic trees showed clade-level consistency but varied in resolution for outbreak isolates.

Conclusions:

Standardized variant calling pipelines are essential for accurate fungal pathogen genomics.
Best practices should address read trimming, SNP calling parameters, and filtration strategies.
Generated truth datasets will aid in benchmarking *C. auris* variant calling and developing future standards.