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Article
Open AccessA scalable platform for efficient CRISPR-Cas9 chemical-genetic screens of DNA damage-inducing compounds
Current approaches to define chemical-genetic interactions (CGIs) in human cell lines are resource-intensive. We designed a scalable chemical-genetic screening platform by generating a DNA damage response (DDR...
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Article
Open AccessDirect structural analysis of a single acyl carrier protein domain in fatty acid synthase from the fungus Saccharomyces cerevisiae
Acyl carrier protein (ACP) is the work horse of polyketide (PKS) and fatty acid synthases (FAS) and acts as a substrate shuttling domain in these mega enzymes. In fungi, FAS forms a 2.6 MDa symmetric assembly ...
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Article
Open AccessN-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity
Most eukaryotic proteins are N-terminally acetylated, but the functional impact on a global scale has remained obscure. Using genome-wide CRISPR knockout screens in human cells, we reveal a strong genetic depe...
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Article
Chemical genomics with pyrvinium identifies C1orf115 as a regulator of drug efflux
Pyrvinium is a quinoline-derived cyanine dye and an approved anti-helminthic drug reported to inhibit WNT signaling and have anti-proliferative effects in various cancer cell lines. To further understand the m...
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Author Correction: Chemical genomics with pyrvinium identifies C1orf115 as a regulator of drug efflux
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Article
BIONIC: biological network integration using convolutions
Biological networks constructed from varied data can be used to map cellular function, but each data type has limitations. Network integration promises to address these limitations by combining and automatical...
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Article
Open AccessTargeting fungal membrane homeostasis with imidazopyrazoindoles impairs azole resistance and biofilm formation
Fungal infections cause more than 1.5 million deaths annually. With an increase in immune-deficient susceptible populations and the emergence of antifungal drug resistance, there is an urgent need for novel st...
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Article
Open AccessHigh-throughput platform for yeast morphological profiling predicts the targets of bioactive compounds
Morphological profiling is an omics-based approach for predicting intracellular targets of chemical compounds in which the dose-dependent morphological changes induced by the compound are systematically compar...
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Article
Open AccessLeveraging machine learning essentiality predictions and chemogenomic interactions to identify antifungal targets
Fungal pathogens pose a global threat to human health, with Candida albicans among the leading killers. Systematic analysis of essential genes provides a powerful strategy to discover potential antifungal targets...
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Article
τ-SGA: synthetic genetic array analysis for systematically screening and quantifying trigenic interactions in yeast
Systematic complex genetic interaction studies have provided insight into high-order functional redundancies and genetic network wiring of the cell. Here, we describe a method for screening and quantifying tri...
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Trigenic Synthetic Genetic Array (τ-SGA) Technique for Complex Interaction Analysis
Complex genetic interactions occur when mutant alleles of multiple genes combine to elicit an unexpected phenotype, which could not be predicted given the expectation based on the combination of phenotypes ass...
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Article
Systematic map** of genetic interactions for de novo fatty acid synthesis identifies C12orf49 as a regulator of lipid metabolism
The de novo synthesis of fatty acids has emerged as a therapeutic target for various diseases, including cancer. Because cancer cells are intrinsically buffered to combat metabolic stress, it is important to u...
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Article
Publisher Correction: Integrating yeast chemical genomics and mammalian cell pathway analysis
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Article
Open AccessDiscovering genetic interactions bridging pathways in genome-wide association studies
Genetic interactions have been reported to underlie phenotypes in a variety of systems, but the extent to which they contribute to complex disease in humans remains unclear. In principle, genome-wide associati...
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Article
Integrating yeast chemical genomics and mammalian cell pathway analysis
Chemical genomics has been applied extensively to evaluate small molecules that modulate biological processes in Saccharomyces cerevisiae. Here, we use yeast as a surrogate system for studying compounds that are ...
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Article
Using BEAN-counter to quantify genetic interactions from multiplexed barcode sequencing experiments
The construction of genome-wide mutant collections has enabled high-throughput, high-dimensional quantitative characterization of gene and chemical function, particularly via genetic and chemical–genetic inter...
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Article
Erratum: Functional annotation of chemical libraries across diverse biological processes
Nat. Chem. Biol. 13, 982–993 (2017); corrected online 7 August 2017 In the version of this article initially published online, there were several typographical errors introducing scientific inaccuracies. In Fi...
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Article
Erratum: Functional annotation of chemical libraries across diverse biological processes
Nat. Chem. Biol. 13, 982–993 (2017); corrected online 7 August 2017; corrected after print 4 October 2017 In the version of this article initially published, the artemisinin structure in Figure 4b was shown wi...
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Article
Open AccessThe Candida albicans transcription factor Cas5 couples stress responses, drug resistance and cell cycle regulation
The capacity to coordinate environmental sensing with initiation of cellular responses underpins microbial survival and is crucial for virulence and stress responses in microbial pathogens. Here we define circ...
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Article
Functional annotation of chemical libraries across diverse biological processes
Profiling of over 13,000 compounds against yeast gene deletion mutants, defining the differential responses on cells, reveals chemical-genetic interactions that can be used to predict compound function and the...
