Insights into the molecular mechanism of anticancer drug ruxolitinib repurposable in COVID-19 therapy

Programming Tools ◽

R Programming ◽

Approved Drugs ◽

AbstractDue to non-availability of specific therapeutics against COVID-19, repurposing of approved drugs is a reasonable option. Cytokines imbalance in COVID-19 resembles cancer; exploration of anti-inflammatory agents, might reduce COVID-19 mortality. The current study investigates the effect of ruxolitinib treatment in SARS-CoV-2 infected alveolar cells compared to the uninfected one from the GSE5147507 dataset. The protein-protein interaction network, biological process and functional enrichment of differentially expressed genes were studied using STRING App of the Cytoscape software and R programming tools. The present study indicated that ruxolitinib treatment elicited similar response equivalent to that of SARS-CoV-2 uninfected situation by inducing defense response in host against virus infection by RLR and NOD like receptor pathways. Further, the effect of ruxolitinib in SARS-CoV-2 infection was mainly caused by significant suppression of IFIH1, IRF7 and MX1 genes as well as inhibition of DDX58/IFIH1-mediated induction of interferon-I and -II signalling.

Network Pharmacology study of Curcuma longa L.: Potential Target Proteins and their Functional Enrichment Analysis.

10.21203/rs.3.rs-31985/v2 ◽

2020 ◽

Author(s):

SANGEETA KUMARI

Keyword(s):

Signaling Pathway ◽

Mechanism Of Action ◽

Protein Interaction ◽

Curcuma Longa ◽

Interaction Network ◽

Functional Enrichment ◽

Target Proteins ◽

Abstract Objective This study’s primary goal is unraveling the mechanism of action of bioactives of Curcuma longa L. at the molecular level using protein-protein interaction network.Results We used target proteins to create protein-protein interaction network (PPIN) and identified significant node and edge attributes of PPIN. We identified the cluster of proteins in the PPIN, which were used to identify enriched pathways. . We identified closeness centrality and jaccard score as most important node and edge attribute of the PPIN respectively. The enriched pathways of various clusters were overlapped suggesting synergistic mechanism of action. The three pathways found to be common among three clusters were Gonadotropin-releasing hormone receptor pathway, Endothelin signaling pathway, and Inflammation mediated by chemokine and cytokine signaling pathway.

Emerging Trends in Applications and Infrastructures for Computational Biology, Bioinformatics, and Systems Biology ◽

A Combination of Protein-Protein Interaction Network Topological and Biological Process Features for Multiprotein Complex Detection

10.1016/b978-0-12-804203-8.00020-1 ◽

2016 ◽

pp. 305-315

Author(s):

N. Zaki ◽

E.A. Mohamed

Keyword(s):

Protein Interaction ◽

Biological Process ◽

Interaction Network ◽

Multiprotein Complex ◽

Complex Detection ◽

Network pharmacology study of Curcuma longa L.: potential target proteins and their functional enrichment analysis

BMC Research Notes ◽

10.1186/s13104-020-05301-0 ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Sangeeta Kumari ◽

Hosahalli S. Subramanya

Keyword(s):

Signaling Pathway ◽

Mechanism Of Action ◽

Protein Interaction ◽

Curcuma Longa ◽

Interaction Network ◽

Functional Enrichment ◽

Target Proteins ◽

Abstract Objective This study’s primary goal is unraveling the mechanism of action of bioactives of Curcuma longa L. at the molecular level using protein–protein interaction network. Results We used target proteins to create protein–protein interaction network (PPIN) and identified significant node and edge attributes of PPIN. We identified the cluster of proteins in the PPIN, which were used to identify enriched pathways. We identified closeness centrality and jaccard score as most important node and edge attribute of the PPIN respectively. The enriched pathways of various clusters were overlapped suggesting synergistic mechanism of action. The three pathways found to be common among three clusters were Gonadotropin-releasing hormone receptor pathway, Endothelin signaling pathway, and Inflammation mediated by chemokine and cytokine signaling pathway.

Identifying Gastric Cancer Related Genes Using the Shortest Path Algorithm and Protein-Protein Interaction Network

BioMed Research International ◽

10.1155/2014/371397 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Yang Jiang ◽

Yang Shu ◽

Ying Shi ◽

Li-Peng Li ◽

Fei Yuan ◽

...

Keyword(s):

Gastric Cancer ◽

Shortest Path ◽

Protein Interaction ◽

High Probability ◽

Biological Process ◽

Interaction Network ◽

Shortest Path Algorithm ◽

Gastric cancer, as one of the leading causes of cancer related deaths worldwide, causes about 800,000 deaths per year. Up to now, the mechanism underlying this disease is still not totally uncovered. Identification of related genes of this disease is an important step which can help to understand the mechanism underlying this disease, thereby designing effective treatments. In this study, some novel gastric cancer related genes were discovered based on the knowledge of known gastric cancer related ones. These genes were searched by applying the shortest path algorithm in protein-protein interaction network. The analysis results suggest that some of them are indeed involved in the biological process of gastric cancer, which indicates that they are the actual gastric cancer related genes with high probability. It is hopeful that the findings in this study may help promote the study of this disease and the methods can provide new insights to study various diseases.

Identifying potential key genes and existing drugs for Multiple sclerosis, Schizophrenia, and Autism- an in silico approach

10.1101/2021.11.30.470019 ◽

2021 ◽

Author(s):

SOUVIK CHAKRABORTY ◽

Sajal Dey ◽

Sushmita Bhowmick

Keyword(s):

Multiple Sclerosis ◽

Interaction Network ◽

Gene Interaction ◽

Autism Spectrum ◽

Interaction Database ◽

Neurological Conditions ◽

Approved Drugs ◽

Fda Approved Drugs ◽

Nowadays, neurological conditions are a major concern as it not only preys on a patients health but also is a huge economic burden that is placed on the patients family. The diagnosis and treatment of disease sometimes cause methodological limitations. This is mainly common for individuals who have the signs of MS and schizophrenia (SZ). Patients suffering from multiple sclerosis are more likely to develop schizophrenia. Besides, a significant portion of patients who have been diagnosed with Autism Spectrum Disorder (ASD) later acquire the symptoms of Schizophrenia. In this study, we used bioinformatics tools to determine differentially expressed genes (DEGs) in all these diseases, and then we created a protein-protein interaction network using the online software STRING and identified 15 significant genes with the help of Cytohubba a plug-in tool in Cytoscape, the offline software (version3.8.2). We then used a drug-gene interaction database to conduct a drug-gene interaction study of the 15 hub genes and from there we showed that there are 37 existing FDA-approved drugs were obtained. These findings may provide a new and common therapeutic approach for MS, SZ, and ASD therapy.

Network Pharmacology study of Curcuma longa L.: Potential Target Proteins and their Functional Enrichment Analysis.

10.21203/rs.3.rs-31985/v3 ◽

2020 ◽

Author(s):

SANGEETA KUMARI ◽

Hosahalli S. Subramanya

Keyword(s):

Signaling Pathway ◽

Mechanism Of Action ◽

Protein Interaction ◽

Curcuma Longa ◽

Interaction Network ◽

Functional Enrichment ◽

Target Proteins ◽

Abstract ObjectiveThis study’s primary goal is unraveling the mechanism of action of bioactives of Curcuma longa L. at the molecular level using protein-protein interaction network.ResultsWe used target proteins to create protein-protein interaction network (PPIN) and identified significant node and edge attributes of PPIN. We identified the cluster of proteins in the PPIN, which were used to identify enriched pathways. We identified closeness centrality and jaccard score as most important node and edge attribute of the PPIN respectively. The enriched pathways of various clusters were overlapped suggesting synergistic mechanism of action. The three pathways found to be common among three clusters were Gonadotropin-releasing hormone receptor pathway, Endothelin signaling pathway, and Inflammation mediated by chemokine and cytokine signaling pathway.

An Analysis of the Anti-Neuropathic Effects of Qi She Pill Based on Network Pharmacology

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/7193832 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15

Author(s):

Yong-jia Song ◽

Jia-min Bao ◽

Long-yun Zhou ◽

Gan Li ◽

Kim Sia Sng ◽

...

Keyword(s):

Mechanism Of Action ◽

Protein Interaction ◽

Biological Process ◽

Interaction Network ◽

Network Pharmacology ◽

Target Network ◽

Protein Protein Interaction Network ◽

Compound Target

Background. Qi She Pill (QSP) is a traditional prescription for the treatment of neuropathic pain (NP) that is widely used in China. However, no network pharmacology studies of QSP in the treatment of NP have been conducted to date. Objective. To verify the potential pharmacological effects of QSP on NP, its components were analyzed via target docking and network analysis, and network pharmacology methods were used to study the interactions of its components. Materials and Methods. Information on pharmaceutically active compounds in QSP and gene information related to NP were obtained from public databases, and a compound-target network and protein-protein interaction network were constructed to study the mechanism of action of QSP in the treatment of NP. The mechanism of action of QSP in the treatment of NP was analyzed via Gene Ontology (GO) biological process annotation and Kyoto Gene and Genomics Encyclopedia (KEGG) pathway enrichment, and the drug-like component-target-pathway network was constructed. Results. The compound-target network contained 60 compounds and 444 corresponding targets. The key active compounds included quercetin and beta-sitosterol. Key targets included PTGS2 and PTGS1. The protein-protein interaction network of the active ingredients of QSP in the treatment of NP featured 48 proteins, including DRD2, CHRM, β2-adrenergic receptor, HTR2A, and calcitonin gene-related peptide. In total, 53 GO entries, including 35 biological process items, 7 molecular function items, and 11 cell related items, were identified. In addition, eight relevant (KEGG) pathways were identified, including calcium, neuroactive ligand-receptor interaction, and cAMP signaling pathways. Conclusion. Network pharmacology can help clarify the role and mechanism of QSP in the treatment of NP and provide a foundation for further research.

Comparative analysis of aneurysm subtypes associated genes based on protein–protein interaction network

BMC Bioinformatics ◽

10.1186/s12859-021-04513-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ruya Sun ◽

Yuan Zhou ◽

Qinghua Cui

Keyword(s):

Protein Interaction ◽

Interaction Network ◽

Functional Enrichment ◽

Arterial Aneurysm ◽

Driver Genes ◽

General Role ◽

Apoptosis Pathway ◽

AbstractThe arterial aneurysm refers to localized dilation of blood vessel wall and is common in general population. The majority of aneurysm cases remains asymptomatic until a sudden rupture which is usually fatal and of extremely high mortality (~ 50–60%). Therefore, early diagnosis, prevention and management of aneurysm are in urgent need. Unfortunately, current understanding of disease driver genes of various aneurysm subtypes is still limited, and without appropriate biomarkers and drug targets no specialized drug has been developed for aneurysm treatment. In this research, aneurysm subtypes were analyzed based on protein–protein interaction network to better understand aneurysm pathogenesis. By measuring network-based proximity of aneurysm subtypes, we identified a relevant closest relationship between aortic aneurysm and aortic dissection. An improved random walk method was performed to prioritize candidate driver genes of each aneurysm subtype. Thereafter, transcriptomes of 6 human aneurysm subtypes were collected and differential expression genes were identified to further filter potential driver genes. Functional enrichment of above driver genes indicated a general role of ubiquitination and programmed cell death in aneurysm pathogenesis. Especially, we further observed participation of BCL-2-mediated apoptosis pathway and caspase-1 related pyroptosis in the development of cerebral aneurysm and aneurysmal subarachnoid hemorrhage in corresponding transcriptomes.