CPA: a web-based platform for consensus pathway analysis and interactive visualization

Nguyen, Hung Son; Tran, Duc; Galazka, Jonathan M.; Costes, Sylvain V.; Beheshti, Afshin; Petereit, Juli; Drăghici, Sorin; Nguyen, Tin

doi:10.1093/nar/gkab421

Cited by 27 publications

(24 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When single cell expression information was assessed by Gene Ontology (GO) Consensus Pathway Analysis (CPA) [ 31 ] the DE genes were found to be related to developmental pathways, mechanotransduction, and genomic stress/repair mechanisms. Figure 2 presents the GO-CPA mapping and expression heatmaps for the highest DE genes from each pathway.…”

Section: Resultsmentioning

confidence: 99%

Differential Single Cell Responses of Embryonic Stem Cells Versus Embryoid Bodies to Gravity Mechanostimulation

Juran

Žvirblytė

Almeida

2022

Stem Cells and Development

View full text Add to dashboard Cite

The forces generated by gravity have shaped life on Earth and impact gene expression and morphogenesis during early development. Conversely, disuse on Earth or during spaceflight, reduces normal mechanical loading of organisms, resulting in altered cell and tissue function. Although gravity mechanical loading in adult mammals is known to promote increased cell proliferation and differentiation, little is known about how distinct cell types respond to gravity mechanostimulation during early development. In this study we sought to understand, with single cell RNA-sequencing resolution, how a 60-min pulse of 50 g hypergravity (HG)/5 kPa hydrostatic pressure, influences transcriptomic regulation of developmental processes in the embryoid body (EB) model. Our study included both day-9 EBs and progenitor mouse embryonic stem cells (ESCs) with or without the HG pulse. Single cell t-distributed stochastic neighbor mapping shows limited transcriptome shifts in response to the HG pulse in either ESCs or EBs; this pulse however, induces greater positional shifts in EB mapping compared to ESCs, indicating the influence of mechanotransduction is more pronounced in later states of cell commitment within the developmental program. More specifically, HG resulted in upregulation of self-renewal and angiogenesis genes in ESCs, while in EBs, HG loading was associated with upregulation of Gene Ontology-pathways for multicellular development, mechanical signal transduction, and DNA damage repair. Cluster transcriptome analysis of the EBs show HG promotes maintenance of transitory cell phenotypes in early development; including EB cluster co-expression of markers for progenitor, post-implant epiblast, and primitive endoderm phenotypes with HG pulse but expression exclusivity in the non-pulsed clusters. Pseudotime analysis identified three branching cell types susceptible to HG induction of cell fate decisions. In totality, this study provides novel evidence that ESC maintenance and EB development can be regulated by gravity mechanostimulation and that stem cells committed to a differentiation program are more sensitive to gravity-induced changes to their transcriptome.

show abstract

Section: Resultsmentioning

confidence: 99%

Differential Single Cell Responses of Embryonic Stem Cells Versus Embryoid Bodies to Gravity Mechanostimulation

Juran

Žvirblytė

Almeida

2022

Stem Cells and Development

View full text Add to dashboard Cite

show abstract

“…KEGG pathway analysis of DEGs showed that enriched pathways included glutathione metabolism and the pentose phosphate pathway, similar to the results obtained from GSE57065 ( Figure 1D ). Consensus pathway analysis (CPA) ( https://bioinformatics.cse.unr.edu/.software/cpa/ ) 26 was used to analyze the ferroptosis-related genes between healthy and septic patients and found that there were 40 kinds of genes that changed after sepsis ( Figure 1E ). Acyl-CoA synthetase long-chain family member 4 (ACSL4), a key indicator and regulator of ferroptosis, which could activate long-chain polyunsaturated fatty acids to participate in the synthesis of membrane phospholipids, was increased significantly in the septic patients with an AUC of 0.854 (95% CI = 0.638–1.000) ( Figure 1F ).…”

Section: Resultsmentioning

confidence: 99%

Protective Effects of Dexmedetomidine on Sepsis-Induced Vascular Leakage by Alleviating Ferroptosis via Regulating Metabolic Reprogramming

She¹,

Hu²,

Zhou³

et al. 2021

JIR

View full text Add to dashboard Cite

Introduction Vascular leakage plays a vital role in sepsis-induced multi-organ dysfunction. Currently, no specific measures are available for vascular leakage. Ferroptosis, as a recently recognized form of cell death, plays a crucial role in cell dysfunction. It is still unknown whether ferroptosis participates in the occurrence of organ dysfunction following sepsis. Our previous study showed that dexmedetomidine (Dex) could alleviate sepsis-induced organ dysfunction. However, whether the mechanism is related to ferroptosis is not clear. Methods The publicly available datasets of septic patients were reanalyzed, and septic models in vivo and vitro by cecal ligation and puncture and lipopolysaccharide-stimulated vascular endothelial cells (VECs) were applied. The occurrence of ferroptosis in septic patients and rats was observed, and the protective effects of Dex on ferroptosis, and related mechanisms on regulating metabolic reprogramming and mitochondrial fission were further studied. Results The transcriptomics data of patients from the GEO database showed that ferroptosis was closely related to sepsis. Sepsis induced significant ferroptosis in VECs by metabolomics analysis. The level of lipid peroxidation was increased in VECs, and the mitochondrial cristae was decreased after sepsis. Metabolomics analysis showed that Dex activated the pentose phosphate pathway and increased glutathione in VECs via up-regulation of G6PD expression. Dex could antagonize sepsis-induced the decrease in the level of Nrf2. The Nrf2 inhibitor reversed the protective effect of Dex on ferroptosis. Further study showed that Dex significantly alleviated sepsis-induced mitochondrial over-division, improved mitochondrial function, and decreased ROS, further inhibiting the ferroptosis of VECs. Dex alleviated the permeability of vessels by reducing ferroptosis and enhanced the intercellular junction of VECs. Conclusion Dex protects vascular leakage following sepsis by inhibiting ferroptosis. The mechanism is mainly related to metabolic reprogramming via Nrf2 up-regulation and inhibition of mitochondrial fission.

show abstract

“…While the techniques to do so can differ, generally a consensus is taken across several methods to determine the final set of pathways that are interesting in some statistically significant way. Examples to do so include the R packages EGSEA [ 58 ], EnrichmentBrowser [ 59 ], Piano [ 60 ] and decoupleR [ 61 ] as well as the ML-based approach, CGPS [ 62 ] and the CPA web application [ 63 ]. Details on each of these ensemble techniques are provided in Supplementary Text 8 (available online at https://academic.oup.com/bib ).…”

Section: Comparative Studies On Enrichment Methodsmentioning

confidence: 99%

On the influence of several factors on pathway enrichment analysis

Mubeen

Kodamullil

Hofmann-Apitius

et al. 2022

Briefings in Bioinformatics

View full text Add to dashboard Cite

Pathway enrichment analysis has become a widely used knowledge-based approach for the interpretation of biomedical data. Its popularity has led to an explosion of both enrichment methods and pathway databases. While the elegance of pathway enrichment lies in its simplicity, multiple factors can impact the results of such an analysis, which may not be accounted for. Researchers may fail to give influential aspects their due, resorting instead to popular methods and gene set collections, or default settings. Despite ongoing efforts to establish set guidelines, meaningful results are still hampered by a lack of consensus or gold standards around how enrichment analysis should be conducted. Nonetheless, such concerns have prompted a series of benchmark studies specifically focused on evaluating the influence of various factors on pathway enrichment results. In this review, we organize and summarize the findings of these benchmarks to provide a comprehensive overview on the influence of these factors. Our work covers a broad spectrum of factors, spanning from methodological assumptions to those related to prior biological knowledge, such as pathway definitions and database choice. In doing so, we aim to shed light on how these aspects can lead to insignificant, uninteresting or even contradictory results. Finally, we conclude the review by proposing future benchmarks as well as solutions to overcome some of the challenges, which originate from the outlined factors.

show abstract

CPA: a web-based platform for consensus pathway analysis and interactive visualization

Cited by 27 publications

References 55 publications

Differential Single Cell Responses of Embryonic Stem Cells Versus Embryoid Bodies to Gravity Mechanostimulation

Differential Single Cell Responses of Embryonic Stem Cells Versus Embryoid Bodies to Gravity Mechanostimulation

Protective Effects of Dexmedetomidine on Sepsis-Induced Vascular Leakage by Alleviating Ferroptosis via Regulating Metabolic Reprogramming

On the influence of several factors on pathway enrichment analysis

Contact Info

Product

Resources

About