VolcaNoseR is a web app for creating, exploring, labeling and sharing volcano plots

Goedhart, Joachim; Luijsterburg, Martijn S.

doi:10.1038/s41598-020-76603-3

Cited by 401 publications

(313 citation statements)

References 14 publications

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“…The SAINT score and the FC_B scores were calculated using the REPRINT (Resource for Evaluation of Protein Interaction Network) online tool (https://reprint-apms.org/). The volcano plot was generated using VolcaNoseR (29). Key putative talin-1 binders, including CDK1, are highlighted.…”

Section: Resultsmentioning

confidence: 99%

Talin mechanosensitivity is modulated by a direct interaction with cyclin-dependent kinase-1

Gough

Jones

Zacharchenko

et al. 2021

Preprint

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Talin is a mechanosensitive component of adhesion complexes that directly couples integrins to the actin cytoskeleton. In response to force, talin undergoes switch-like behaviour of its multiple rod domains that modulate interactions with its binding partners. Cyclin-dependent kinase-1 (CDK1) is a key regulator of the cell cycle, exerting its effects through synchronised phosphorylation of a large number of protein targets. CDK1 activity also maintains adhesion during interphase, and its inhibition is a prerequisite for the tightly choreographed changes in cell shape and adhesiveness that are required for successful completion of mitosis. Using a combination of biochemical, structural and cell biological approaches, we demonstrate a direct interaction between talin and CDK1 that occurs at sites of integrin- mediated adhesion. Mutagenesis demonstrated that CDK1 contains a functional talin-binding LD motif, and the binding site within talin was pinpointed to helical bundle R8 through the use of recombinant fragments. Talin also contains a consensus CDK1 phosphorylation motif centred on S1589; a site that was phosphorylated by CDK1 in vitro. A phosphomimetic mutant of this site within talin lowered the binding affinity of KANK and weakened the mechanical response of the region, potentially altering downstream mechanotransduction pathways. The direct binding of the master cell cycle regulator, CDK1, to the primary integrin effector, talin, therefore provides a primordial solution for coupling the cell proliferation and cell adhesion machineries, and thereby enables microenvironmental control of cell division in multicellular organisms.

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Section: Resultsmentioning

confidence: 99%

Talin mechanosensitivity is modulated by a direct interaction with cyclin-dependent kinase-1

Gough

Jones

Zacharchenko

et al. 2021

Preprint

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“…All plots were generated in R using the following additional libraries: ggplot2 graphing package, ggbeeswarm for column scatterplots, ggExtra for marginal histograms and ComplexHeatMap for heatmaps. Volcano plots were generated with VolcaNoseR ( Goedhart and Luijsterburg, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Variability of an Early Developmental Cell Population Underlies Stochastic Laterality Defects

et al. 2021

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“…Differential expression analysis was performed using the DESeq2 R package (133) using a custom R script ( SUPP FILE 5 ) with a Benjamini-Hochberg adjusted P -value cut-off of <= 0.05. The volcano plot presented in Figure S3 was generated using VolcaNoseR (134).…”

Section: Methodsmentioning

confidence: 99%

The SAGA and NuA4 component Tra1 regulatesCandida albicansdrug resistance and pathogenesis

Razzaq

Berg

Jiang

et al. 2021

Preprint

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Candida albicans is the most common cause of death from fungal infections. Emergence of resistant strains reducing the efficacy of first line therapy with echinocandins such as caspofungin calls for the identification of alternative therapeutic strategies. Tra1 is an essential component of the SAGA and NuA4 transcriptional co-activator complexes. As a PIKK family member, Tra1 is characterized by a C-terminal phosphoinositide 3-kinase domain. In Saccharomyces cerevisiae, the assembly and function of SAGA and NuA4 is compromised by a version of Tra1 (Tra1Q3) with three arginine residues in the putative ATP-binding cleft changed to glutamine, Whole transcriptome analysis of the S. cerevisiae tra1Q3 strain highlights Tra1’s role in global transcription, stress response and cell wall integrity. As a result, tra1Q3 increases susceptibility to multiple stressors, including caspofungin. Moreover, the same tra1Q3 allele in the pathogenic yeast Candida albicans causes similar phenotypes, suggesting that Tra1 broadly mediates the antifungal response across yeast species. Transcriptional profiling in C. albicans identified 68 genes that were differentially expressed when the tra1Q3 strain was treated with caspofungin, as compared to gene expression changes induced by either tra1Q3 or caspofungin alone. Included in this set were genes involved in cell wall maintenance, adhesion and filamentous growth. Indeed, the tra1Q3 allele reduces filamentation and other pathogenesis traits in C. albicans. We identified EVP1, which encodes a putative plasma membrane protein, amongst the Tra1-regulated genes, Disrupting EVP1 results in reduced filamentation and infection capacity in C. albicans. Thus,Tra1 emerges as a promising therapeutic target for fungal infections.ImportanceFungal pathogens such as Candida albicans are important agents of infectious disease, with increasing rates of drug resistance, and limited available antifungal therapeutics. In this study, we characterize the role of C. albicans Tra1, a critical component of acetyltransferase complexes, involved in transcriptional regulation and responses to environmental stress. We find C. albicans genetic mutants with impaired Tra1 function have reduced tolerance to cell-wall targeting stressors, including the clinically-important antifungal caspofungin. We further use RNA-sequencing to profile the global fungal response to the tra1 mutation, and identify a previously uncharacterized C. albicans gene, EVP1. We find that both TRA1 and EVP1 play an important role in phenotypes associated with fungal pathogenesis, including cellular morphogenesis, biofilm formation, and toxicity towards host immune cells. Together, this work describes the key role for Tra1 in regulating fungal drug tolerance and pathogenesis, and positions this protein as a promising therapeutic target for fungal infections.

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VolcaNoseR is a web app for creating, exploring, labeling and sharing volcano plots

Cited by 401 publications

References 14 publications

Talin mechanosensitivity is modulated by a direct interaction with cyclin-dependent kinase-1

Talin mechanosensitivity is modulated by a direct interaction with cyclin-dependent kinase-1

Variability of an Early Developmental Cell Population Underlies Stochastic Laterality Defects

The SAGA and NuA4 component Tra1 regulatesCandida albicansdrug resistance and pathogenesis

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