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Scherens, Bart; Goffeau, André

doi:10.1186/gb-2004-5-7-229

Cited by 102 publications

(36 citation statements)

References 61 publications

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“…Since their first publication in 1999, the barcoded budding yeast deletion collections have markedly accelerated the pace of discovery in diverse fields that can take advantage of a yeast model [3,63]. We expect that the method we report in this paper will help the barcoded fission yeast deletion collections fulfill their potential and make far-reaching contributions in the coming years.…”

Section: Discussionmentioning

confidence: 99%

Global fitness profiling of fission yeast deletion strains by barcode sequencing

Han

Zhang

et al. 2010

Genome Biol

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Section: Discussionmentioning

confidence: 99%

Global fitness profiling of fission yeast deletion strains by barcode sequencing

Han

Zhang

et al. 2010

Genome Biol

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“…Each knockout strain is marked by two unique 20-bp barcodes, allowing quantitative and qualitative identification [32]. …”

Section: Functional Genomics In Yeastmentioning

confidence: 99%

Functional genomic screening approaches in mechanistic toxicology and potential future applications of CRISPR-Cas9

Shen¹,

McHale²,

Smith³

et al. 2015

Mutation Research/Reviews in Mutation Research

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Characterizing variability in the extent and nature of responses to environmental exposures is a critical aspect of human health risk assessment. Chemical toxicants act by many different mechanisms, however, and the genes involved in adverse outcome pathways (AOPs) and AOP networks are not yet characterized. Functional genomic approaches can reveal both toxicity pathways and susceptibility genes, through knockdown or knockout of all non-essential genes in a cell of interest, and identification of genes associated with a toxicity phenotype following toxicant exposure. Screening approaches in yeast and human near-haploid leukemic KBM7 cells, have identified roles for genes and pathways involved in response to many toxicants but are limited by partial homology among yeast and human genes and limited relevance to normal diploid cells. RNA interference (RNAi) suppresses mRNA expression level but is limited by off-target effects (OTEs) and incomplete knockdown. The recently developed gene editing approach called clustered regularly interspaced short palindrome repeats-associated nuclease (CRISPR)-Cas9, can precisely knock-out most regions of the genome at the DNA level with fewer OTEs than RNAi, in multiple human cell types, thus overcoming the limitations of the other approaches. It has been used to identify genes involved in the response to chemical and microbial toxicants in several human cell types and could readily be extended to the systematic screening of large numbers of environmental chemicals. CRISPR-Cas9 can also repress and activate gene expression, including that of non-coding RNA, with near-saturation, thus offering the potential to more fully characterize AOPs and AOP networks. Finally, CRISPR-Cas9 can generate complex animal models in which to conduct preclinical toxicity testing at the level of individual genotypes or haplotypes. Therefore, CRISPR-Cas9 is a powerful and flexible functional genomic screening approach that can be harnessed to provide unprecedented mechanistic insight in the field of modern toxicology.

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“…These genome-scale genetic interactions studies were facilitated by the availability of large collections of deletion strains and the development of automated platforms to analyze the phenotypes of double mutants (Scherens and Goffeau, 2004). Since the first large-scale genetic interaction study in yeast identified 4000 genetic interactions among 1000 genes when analyzing synthetic lethality in double deletion mutants (Tong et al, 2004), the field advanced considerably.…”

Section: Introductionmentioning

confidence: 99%

Combining growth-promoting genes leads to positive epistasis in Arabidopsis thaliana

Vanhaeren

González

Coppens

et al. 2014

eLife

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Several genes positively influence final leaf size in Arabidopsis when mutated or overexpressed. The connections between these growth regulators are still poorly understood although such knowledge would further contribute to understand the processes driving leaf growth. In this study, we performed a combinatorial screen with 13 transgenic Arabidopsis lines with an increased leaf size. We found that from 61 analyzed combinations, 39% showed an additional increase in leaf size and most resulted from a positive epistasis on growth. Similar to what is found in other organisms in which such an epistasis assay was performed, only few genes were highly connected in synergistic combinations as we observed a positive epistasis in the majority of the combinations with samba, BRI1OE or SAUR19OE. Furthermore, positive epistasis was found with combinations of genes with a similar mode of action, but also with genes which affect distinct processes, such as cell proliferation and cell expansion.DOI: http://dx.doi.org/10.7554/eLife.02252.001

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Untitled

Cited by 102 publications

References 61 publications

Global fitness profiling of fission yeast deletion strains by barcode sequencing

Global fitness profiling of fission yeast deletion strains by barcode sequencing

Functional genomic screening approaches in mechanistic toxicology and potential future applications of CRISPR-Cas9

Combining growth-promoting genes leads to positive epistasis in Arabidopsis thaliana

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