The STRING database in 2023: protein–protein association networks and functional enrichment analyses for any sequenced genome of interest

Szklarczyk, Damian; Kirsch, Rebecca; Koutrouli, Mikaela; Nastou, Katerina C.; Mehryary, Farrokh; Hachilif, Radja; Gable, Annika L.; Fang, Tao; Doncheva, Nadezhda T.; Pyysalo, Sampo; Bork, Peer; Jensen, Lars Juhl; Mering, Christian von

doi:10.1093/nar/gkac1000

Cited by 1,269 publications

(719 citation statements)

References 74 publications

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“…A p − value less than 0.01 (after correction for multiple tests) was considered significant. Functional enrichment of the list of the genes was performed by the Gene Ontology portal http://geneontology.org/ and by using STRING database [70].…”

Section: Discussionmentioning

confidence: 99%

Analysis of age-dependent gene-expression in human tissues for diabetes comorbidities.

Guzzi¹,

Cortese²,

Mannino³

et al. 2023

Preprint

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The study of the relations of type 2 diabetes mellitus (T2DM) disease with other pathologies (comorbidities) together with patient age variation poses a challenge for medical research. There is evidence that patients affected by T2DM are more likely to develop comorbidities as they grow older. Variation of gene expression can be related to changes in T2DM comorbidities insurgence and progression. Understanding gene expression changes requires the analysis of large heterogeneous data at different scale as well as the integration of different data sources into network medicine models. Hence, we designed a framework to shed light on uncertainties related to age effects and comorbidity by integrating existing data sources with novel algorithms. The framework is based on the integration and analysis of existing data sources under the hypothesis that changes in the basal expression of genes may be responsible of the higher prevalence of comorbidities in older patients. Using the proposed framework, we selected genes related to comorbidities from existing databases, then analysed their expression with age at the tissues level. We found a set of genes that changes significantly in certain specific tissues over time. We also reconstructed the associated protein interaction networks and the related pathways for each tissue. Using this mechanistic framework we detected interesting pathways related to T2DM whose genes change their expression with age. We also found many pathways related to insulin regulation and brain activities, which can be used to develop specific therapies. To the best of our knowledge, this is the first study that analyses such genes at the tissue level together with age variations.

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Section: Discussionmentioning

confidence: 99%

Analysis of age-dependent gene-expression in human tissues for diabetes comorbidities.

Guzzi¹,

Cortese²,

Mannino³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…After that, we used Xiantao tool ( https://www.xiantao.love/products ) to analyze the Gene ontology (GO) enrichment of AKR1C2 co-expressed genes. Furthermore, we have utilized the STRING [ 21 ] to analyze the protein-protein network of AKR1C2. Next, the single-sample GSEA (ssGSEA) [ 22 ] was conducted to explore the correlation between AKR1C2 level and 24 types of TIICs in GC.…”

Section: Methodsmentioning

confidence: 99%

Comprehensive analysis regarding the prognostic significance of downregulated ferroptosis-related gene AKR1C2 in gastric cancer and its underlying roles in immune response

et al. 2023

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Ferroptosis is a cell death form that has been reported to be involved in the progression of gastric cancer (GC). However, the underlying mechanism of ferroptosis in GC still needs to be further explored. This study conducted a survey regarding the biological functions of ferroptosis-related gene AKR1C2 in GC. Multiple bioinformatic platforms were applied to indicate that the expression level of AKR1C2 was downregulated in GC tissues, which displayed good prognostic value. Clinical statistics proved that AKR1C2 expression was correlated with several tumor characteristics of GC patients, such as characteristics of N-stage tumor or residual tumor. Additionally, LinkedOmics was employed to explore the co-expression network and molecular pathways of AKR1C2 in GC. Eventually, AKR1C2 was found to be involved in several immune-related signatures, such as immunostimulators, immunoinhibitors, chemokines and chemokine receptors. To sum up, these results may provide a novel insight into the significance and biological functions of ferroptosis-related gene AKR1C2 in GC tumorigenesis.

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“…The genes mapped to STRING database 1 were selected to construct Protein–protein interaction (PPI) network ( 15 ). Cytoscape software (version 3.9.1 2 ) performed the network visualization and analysis ( 16 ).…”

Section: Methodsmentioning

confidence: 99%

Comprehensive analysis of transcriptomics and metabolomics to understand tail-suspension-induced myocardial injury in rat

Guo²,

Xu³

et al. 2023

Front. Cardiovasc. Med.

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Background/AimsThe effect and underlying mechanism of microgravity on myocardium still poorly understood. The present study aims to reveal the effect and underlying mechanism of tail-suspension-induced microgravity on myocardium of rats.MethodsTail-suspension was conducted to simulate microgravity in rats. Echocardiography assay was used to detect cardiac function. The cardiac weight index was measured. Hematoxylin and eosin (HE) staining and transmission electron microscopy assay were conducted to observe the structure of the tissues. RNA sequencing and non-targeted metabolomics was employed to obtain transcriptome and metabolic signatures of heart from tail-suspension-induced microgravity and control rats.ResultsMicrogravity induced myocardial atrophy and decreased cardiac function in rats. Structure and ultrastructure changes were observed in myocardium of rats stimulated with microgravity. RNA sequencing for protein coding genes was performed and identified a total of 605 genes were differentially expressed in myocardium of rats with tail suspension, with 250 upregulated and 355 downregulated (P < 0.05 and | log2fold change| > 1). A total of 55 differentially expressed metabolites were identified between the two groups (VIP > 1 and P < 0.05) by the metabolic profiles of heart tissues from microgravity groups and control. Several major pathways altered aberrantly at both transcriptional and metabolic levels, including FoxO signaling pathway, Amyotrophic lateral sclerosis, Histidine metabolism, Arginine and proline metabolism.ConclusionMicrogravity can induce myocardial atrophy and decreases cardiac function in rats and the molecular alterations at the metabolic and transcriptomic levels was observed, which indicated major altered pathways in rats with tail suspension. The differentially expressed genes and metabolites-involved in the pathways maybe potential biomarkers for microgravity-induced myocardial atrophy.

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The STRING database in 2023: protein–protein association networks and functional enrichment analyses for any sequenced genome of interest

Cited by 1,269 publications

References 74 publications

Analysis of age-dependent gene-expression in human tissues for diabetes comorbidities.

Analysis of age-dependent gene-expression in human tissues for diabetes comorbidities.

Comprehensive analysis regarding the prognostic significance of downregulated ferroptosis-related gene AKR1C2 in gastric cancer and its underlying roles in immune response

Comprehensive analysis of transcriptomics and metabolomics to understand tail-suspension-induced myocardial injury in rat

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