Researchers have built a new genetic barcoding library, called BarMix, that captures the natural diversity of the yeast Saccharomyces cerevisiae and enables high-throughput fitness profiling across hundreds of strains.
Few existing barcoded libraries capture this natural variation, which the authors describe as a rich reservoir of genetic variation for functional genomic screens.
To test the platform, the researchers profiled the pooled library by barcode-sequencing against 33 small-molecule compounds with diverse bioactivities. Through genome-wide association analysis, they identified 281 chemogenomic interactions linking genetic variants to drug responses.
Chemical fitness signatures differed between domesticated and wild clades, particularly under stresses affecting ergosterol biosynthesis, DNA alkylation, microtubule depolymerisation, TORC1 inactivation, and membrane permeability.
The team validated seven associated alleles through allele-swap experiments. These included variants in genes that modulate multidrug export (Yrr1), tRNA-specificity (ArgRS), and small-molecule methylation (Crg1).
Several of the validated alleles displayed variable penetrance across strains, which the authors say suggests a complex genetic basis for trait variation. Importantly, including admixture into the genome-wide association design enhanced variant detection in S. cerevisiae.
The researchers conclude that these results establish BarMix as a platform for genotype-phenotype discovery with applications in functional genomics and biotechnology, and highlight the value of incorporating natural variation into model-systems biology.
Subject of Research: A CRISPR-Cas9 barcoded yeast library for chemogenomic fitness profiling across diverse Saccharomyces cerevisiae strains
Article Title: Chemogenomic profiling of diverse Saccharomyces cerevisiae strains using the novel CRISPR-Cas9 markerless barcoded library BarMix
Article References: Moore, J., Barazandeh, M., Nislow, C., & Measday, V. (2026). Chemogenomic profiling of diverse Saccharomyces cerevisiae strains using the novel CRISPR-Cas9 markerless barcoded library BarMix. Genome Biology. https://doi.org/10.1186/s13059-026-04319-0
Image Credits: AI Generated
DOI: 10.1186/s13059-026-04319-0
Keywords: Saccharomyces cerevisiae, BarMix, CRISPR-Cas9, chemogenomics, barcode sequencing, genome-wide association, allele swaps, functional genomics, yeast diversity, drug response, Chemogenomic, profiling
News Source: Juliet Wilcox. (October 28, 2026). New Barcoded Yeast Library Maps Gene-Drug Interactions Across 262 Strains. Scienmag.
