g:Profiler—interoperable web service for functional enrichment analysis and gene identifier mapping (2023 update)

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

doi:10.1093/nar/gkad347

Cited by 253 publications

(145 citation statements)

References 28 publications

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“…While the Magenta and Yellow modules revealed a weak positive correlation of (0.48 p ‐value 3.5e–10), three other modules, namely Greenyellow and Blue (−0.77 p ‐value 0.0), Brown and Salmon (−0.7 p ‐value 0.0), and Turquoise and Purple (−0.63 p ‐value 0.0), exhibited a strong negative correlation between each pair, respectively. We then mapped the genes across these modules onto pathways following an overrepresentation analysis using the g:Profiler suite 27 . The resulting negative correlated GO enrichment terms associated with each module were then statistically compared to the overall association of all human genes (Figure S1).…”

Section: Resultsmentioning

confidence: 99%

Analysis of translesion polymerases in colorectal cancer cells following cetuximab treatment: A network perspective

Das,

Gkoutos,

Acharjee

2024

Cancer Medicine

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IntroductionAdaptive mutagenesis observed in colorectal cancer (CRC) cells upon exposure to EGFR inhibitors contributes to the development of resistance and recurrence. Multiple investigations have indicated a parallel between cancer cells and bacteria in terms of exhibiting adaptive mutagenesis. This phenomenon entails a transient and coordinated escalation of error‐prone translesion synthesis polymerases (TLS polymerases), resulting in mutagenesis of a magnitude sufficient to drive the selection of resistant phenotypes.MethodsIn this study, we conducted a comprehensive pan‐transcriptome analysis of the regulatory framework within CRC cells, with the objective of identifying potential transcriptome modules encompassing certain translesion polymerases and the associated transcription factors (TFs) that govern them. Our sampling strategy involved the collection of transcriptomic data from tumors treated with cetuximab, an EGFR inhibitor, untreated CRC tumors, and colorectal‐derived cell lines, resulting in a diverse dataset. Subsequently, we identified co‐regulated modules using weighted correlation network analysis with a minKMEtostay threshold set at 0.5 to minimize false‐positive module identifications and mapped the modules to STRING annotations. Furthermore, we explored the putative TFs influencing these modules using KBoost, a kernel PCA regression model.ResultsOur analysis did not reveal a distinct transcriptional profile specific to cetuximab treatment. Moreover, we elucidated co‐expression modules housing genes, for example, POLK, POLI, POLQ, REV1, POLN, and POLM. Specifically, POLK, POLI, and POLQ were assigned to the “blue” module, which also encompassed critical DNA damage response enzymes, for example. BRCA1, BRCA2, MSH6, and MSH2. To delineate the transcriptional control of this module, we investigated associated TFs, highlighting the roles of prominent cancer‐associated TFs, such as CENPA, HNF1A, and E2F7.ConclusionWe found that translesion polymerases are co‐regulated with DNA mismatch repair and cell cycle‐associated factors. We did not, however, identified any networks specific to cetuximab treatment indicating that the response to EGFR inhibitors relates to a general stress response mechanism.

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Section: Resultsmentioning

confidence: 99%

Analysis of translesion polymerases in colorectal cancer cells following cetuximab treatment: A network perspective

Das,

Gkoutos,

Acharjee

2024

Cancer Medicine

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“…The target gene module identified from WGCNA containing HvHGGT was selected for GO enrichment analyses using the g:Profiler online tool at https://biit.cs.ut.ee/gprofiler/ (last accessed on 31st Oct 2023). 29 Gene ID in Morex V3 were used as input for the g:GOSt function in g:Profiler. Gene Ontology (GO) enrichment (P-value threshold of 0.05) was performed using hypergeometric distribution tests and adjusted by multiple testing corrections using the g:SCS algorithm.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…The target gene module identified from WGCNA containing HvHGGT was selected for GO enrichment analyses using the g:Profiler online tool at (last accessed on 31st Oct 2023) . Gene ID in Morex V3 were used as input for the g:GOSt function in g:Profiler.…”

Section: Methodsmentioning

confidence: 99%

Coordinated Transcriptome and Metabolome Analyses of a Barley hvhggt Mutant Reveal a Critical Role of Tocotrienols in Endosperm Starch Accumulation

Zeng,

Zhang,

Shi

et al. 2024

J. Agric. Food Chem.

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Tocotrienols and tocopherols (vitamin E) are potent antioxidants that are synthesized in green plants. Unlike ubiquitous tocopherols, tocotrienols predominantly accumulate in the endosperm of monocot grains, catalyzed by homogentiate geranylgeranyl transferase (HGGT). Previously, we generated a tocotrienol-deficient hvhggt mutant with shrunken barley grains. However, the relationship between tocotrienols and grain development remains unclear. Here, we found that the hvhggt lines displayed hollow endosperms with defective transfer cells and reduced aleurone layers. The carbohydrate and starch contents of the hvhggt endosperm decreased by approximately 20 and 23%, respectively. Weighted gene coexpression network analyses identified a critical gene module containing HvHGGT, which was strongly associated with the hvhggt mutation and enriched with gene functions in starch and sucrose metabolism. Metabolome measurements revealed an elevated soluble sugar content in the hvhggt endosperm, which was significantly associated with the identified gene modules. The hvhggt endosperm had significantly higher NAD(H) and NADP(H) contents and lower levels of ADPGlc (regulated by redox balance) than the wild-type, consistent with the absence of tocotrienols. Interestingly, exogenous α-tocotrienol spraying on developing hvhggt spikes partially rescued starch accumulation and endosperm defects. Our study supports a potential novel function of tocotrienols in grain starch accumulation and endosperm development in monocot crops.

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“…Enriched cellular components were identified utilizing the GO cellular functions data source of g:Profiler (Kolberg et al, 2023). The regulator network analysis was generated through the use of QIAGEN IPA (QIAGEN Inc., https://digitalinsights.qiagen.com/IPA) (Kramer et al, 2014).…”

Section: Rna Sequencing and Transcriptomic Analysismentioning

confidence: 99%

ACKR3 in olfactory glia cells shapes the immune defense of the olfactory mucosa

Dietz,

Senf,

Neuhaus

2024

Glia

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Barrier‐forming olfactory glia cells, termed sustentacular cells, play important roles for immune defense of the olfactory mucosa, for example as entry sites for SARS‐CoV‐2 and subsequent development of inflammation‐induced smell loss. Here we demonstrate that sustentacular cells express ACKR3, a chemokine receptor that functions both as a scavenger of the chemokine CXCL12 and as an activator of alternative signaling pathways. Differential gene expression analysis of bulk RNA sequencing data obtained from WT and ACKR3 conditional knockout mice revealed upregulation of genes involved in immune defense. To map the regulated genes to the different cell types of the olfactory mucosa, we employed biocomputational methods utilizing a single‐cell reference atlas. Transcriptome analysis, PCR and immunofluorescence identified up‐regulation of NF‐κB‐related genes, known to amplify inflammatory signaling and to facilitate leukocyte transmigration, in the gliogenic lineage. Accordingly, we found a marked increase in leukocyte‐expressed genes and confirmed leukocyte infiltration into the olfactory mucosa. In addition, lack of ACKR3 led to enhanced expression and secretion of early mediators of immune defense by Bowman's glands. As a result, the number of apoptotic cells in the epithelium was decreased. In conclusion, our research underlines the importance of sustentacular cells in immune defense of the olfactory mucosa. Moreover, it identifies ACKR3, a druggable G protein‐coupled receptor, as a promising target for modulation of inflammation‐associated anosmia.

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g:Profiler—interoperable web service for functional enrichment analysis and gene identifier mapping (2023 update)

Cited by 253 publications

References 28 publications

Analysis of translesion polymerases in colorectal cancer cells following cetuximab treatment: A network perspective

Analysis of translesion polymerases in colorectal cancer cells following cetuximab treatment: A network perspective

Coordinated Transcriptome and Metabolome Analyses of a Barley hvhggt Mutant Reveal a Critical Role of Tocotrienols in Endosperm Starch Accumulation

ACKR3 in olfactory glia cells shapes the immune defense of the olfactory mucosa

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