gprofiler2 -- an R package for gene list functional enrichment analysis and namespace conversion toolset g:Profiler

Kolberg, Liis; Raudvere, Uku; Kuzmin, Ivan; Vilo, Jaak; Peterson, Hedi

doi:10.12688/f1000research.24956.1

Cited by 222 publications

(160 citation statements)

References 28 publications

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“…Permutational multivariate analysis of variance (PERMANOVA) was calculated using the vegan package [33]. GO analysis was carried out using the gprofiler2 package [34]. Gene Set Enrichment Analysis (GSEA) was carried out using GSEA software (Broad Institute, version 4.0.2) and Reactome, KEGG and Biocarta pathways databases [35].…”

Section: Methodsmentioning

confidence: 99%

Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature

Amorim

Novais

Nguyen

et al. 2020

Preprint

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Cutaneous leishmaniasis is a localized infection controlled by CD4+ T cells that produce IFN-γ within lesions. Phagocytic cells recruited to lesions, such as monocytes, are then exposed to IFN-γ which triggers their ability to kill the intracellular parasites. Consistent with this, a transcriptional analysis of lesions from patients identified the presence of a strong interferon stimulated gene (ISG) signature. To determine what systemic responses are occurring that might influence the disease, we performed RNA sequencing (RNA-seq) on the blood of L. braziliensis-infected patients, as well as healthy controls. Functional enrichment analysis identified a transcriptional ISG signature as the dominant response in the blood of patients. An increase in monocytes and macrophages in the blood, estimated from our RNA-seq dataset, was positively correlated with this ISG signature. Consistent with this result, patients had circulating IFN-γ in their serum. A cytotoxicity signature, which is a dominant feature in the lesions, was also found in the blood and correlated with an increased abundance of cytolytic cells. Thus, two transcriptional signatures present in lesions were found systemically, although with a substantially reduced number of differentially expressed genes (DEGs). Finally, we found that the number of DEGs and ISGs in leishmaniasis was similar to tuberculosis – another localized infection – but significantly less than observed in malaria. In contrast, the cytolytic signature and increased cytolytic cell abundance was not found in tuberculosis or malaria. Our results indicate that systemic signatures can reflect what is occurring in leishmanial lesions. Furthermore, the presence of an ISG signature in blood monocytes and macrophages suggests a mechanism to limit systemic spread of the parasite, as well as enhance parasite control by pre-activating cells prior to lesion entry.Author summaryCutaneous leishmaniasis caused by the protozoan Leishmania braziliensis exhibits two dominant inflammatory responses in cutaneous lesions: Interferon-γ (IFN-γ)-mediated signaling, which promotes parasite control, and cytolysis mediated by cytotoxic CD8+ T and NK cells, which promotes increased pathology. To determine if these responses were limited to cutaneous lesions, we performed RNA-seq on the blood of cutaneous leishmaniasis (CL) patients, and detected both transcriptional signatures in the peripheral blood. The presence of interferon stimulated genes, as well as circulating IFN-γ, suggests that protective immune responses are not limited to the lesion site, but are occurring systemically. This may be one mechanism to ensure optimal control of the parasites, both by limiting their systemic spread and by pre-activating cells to kill the parasites prior to entry into the lesions. The cytolytic transcriptional signature was uniquely detectable in the blood of L. braziliensis patients when compared to the blood of patients with tuberculosis (TB) or malaria, further emphasizing the importance of this pathway in cutaneous leishmaniasis. Taken together, these data suggest that this localized infection has a systemic component that may have an impact the development of the disease.

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Section: Methodsmentioning

confidence: 99%

Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature

Amorim

Novais

Nguyen

et al. 2020

Preprint

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“…Differential gene expression analysis determines lists of genes that show changes in expression between different conditions, cell types, time points, etc. Functional enrichment analysis using the gprofiler2 package 8 helps to interpret these gene lists.…”

Section: Use Casementioning

confidence: 99%

“…Providing users with fast and easy access has been the main goal of g:Profiler developers. Since 2007, g:Profiler has been in constant development and with the recent update in 2019 a new accompanying R package, gprofiler2, was developed 8 . The R package relies on the g:Profiler REST API requests providing an easy programmatic access to the same functionalities as in the web tool without performing heavy computations and mappings in R. While there are other popular R packages for functional enrichment analysis, such as topGO 9 and clusterProfiler 10 , gprofiler2 provides access to numerous annotation data sources with a single query without requiring to download any of these sources to a local computer.…”

Section: Introductionmentioning

confidence: 99%

gprofiler2 -- an R package for gene list functional enrichment analysis and namespace conversion toolset g:Profiler

et al. 2020

Self Cite

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g:Profiler (https://biit.cs.ut.ee/gprofiler) is a widely used gene list functional profiling and namespace conversion toolset that has been contributing to reproducible biological data analysis already since 2007. Here we introduce the accompanying R package, gprofiler2, developed to facilitate programmatic access to g:Profiler computations and databases via REST API. The gprofiler2 package provides an easy-to-use functionality that enables researchers to incorporate functional enrichment analysis into automated analysis pipelines written in R. The package also implements interactive visualisation methods to help to interpret the enrichment results and to illustrate them for publications. In addition, gprofiler2 gives access to the versatile gene/protein identifier conversion functionality in g:Profiler enabling to map between hundreds of different identifier types or orthologous species. The gprofiler2 package is freely available at the CRAN repository.

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“…Genes that were identified as significantly differentially expressed (defined as -1<logFC>1, p<0.05) during prior differential gene expression analysis were used for functional enrichment analysis using the R package gprofiler2 (Kolberg et al, 2020). Enrichment analysis was performed on multiple input lists containing genes expressed significantly higher (logFC > 1, P < 0.05) and lower (logFC < -1, P < 0.05) between different patient cohorts.…”

Section: Functional Enrichment Analysis Of Differentially Expressed Cmentioning

confidence: 99%

Gene expression profiling of malaria parasites reveals common virulence gene expression in adult first-time infected patients and severe cases

Wichers

Tonkin‐Hill

Thye

et al. 2020

Preprint

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Sequestration of Plasmodium falciparum-infected erythrocytes to host endothelium through the parasite-derived PfEMP1 adhesion proteins, is central to the development of malaria pathogenesis. PfEMP1 proteins have diversified and expanded to encompass many sequence variants conferring the same array of human endothelial receptor binding phenotypes. Here, we analyzed RNA-seq profiles of parasites isolated from 32 infected travelers returning to Germany. Patients were categorized into either malaria naïve (n=15) or pre-exposed (n=17), and into severe (n=8) or non-severe (n=24) cases. Expression analysis of PfEMP1-encoding var genes showed that severe malaria was associated with expression of PfEMP1 containing the endothelial protein C receptor (EPCR)-binding CIDRα1 domain, whereas CD36-binding PfEMP1 was linked to non-severe malaria outcomes. In addition, gene expression-guided determination of parasite age, suggested that circulating parasites from non-severe malaria patients were older than parasites from severe malaria patients. First-time infected patients were also more likely to develop severe symptoms and tended to be infected for a longer period, which thus appeared to select for parasites with more sequestration-efficiency and therefore more pathogenic PfEMP1 variants.

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gprofiler2 -- an R package for gene list functional enrichment analysis and namespace conversion toolset g:Profiler

Cited by 222 publications

References 28 publications

Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature

Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature

gprofiler2 -- an R package for gene list functional enrichment analysis and namespace conversion toolset g:Profiler

Gene expression profiling of malaria parasites reveals common virulence gene expression in adult first-time infected patients and severe cases

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