Constructing the angiome: a global angiogenesis protein interaction network

Angiogenesis is the formation of new blood vessels from pre-existing microvessels. Excessive and insufficient angiogenesis have been associated with many diseases including cancer, age-related macular degeneration, ischemic heart, brain, and skeletal muscle diseases. A comprehensive understanding of angiogenesis regulatory processes is needed to improve treatment of these diseases. To identify proteins related to angiogenesis, we developed a novel integrative framework for diverse sources of high-throughput data. The system, called GeneHits, was used to expand on known angiogenesis pathways to construct the angiome, a protein-protein interaction network for angiogenesis. The network consists of 478 proteins and 1,488 interactions. The network was validated through cross validation and analysis of five gene expression datasets from in vitro angiogenesis assays. We calculated the topological properties of the angiome. We analyzed the functional enrichment of angiogenesis-annotated and associated proteins. We also constructed an extended angiome with 1,233 proteins and 5,726 interactions to derive a more complete map of protein-protein interactions in angiogenesis. Finally, the extended angiome was used to identify growth factor signaling networks that drive angiogenesis and antiangiogenic signaling networks. The results of this analysis can be used to identify genes and proteins in different disease conditions and putative targets for therapeutic interventions as high-ranked candidates for experimental validation.

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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 ◽

Protein Interaction Network ◽

Curcuma Longa ◽

Interaction Network ◽

Functional Enrichment ◽

Target Proteins ◽

Protein Protein Interaction ◽

Protein Protein Interaction Network

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.

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Microarray analysis of novel genes involved in HSV-2 infection

10.21203/rs.3.rs-517057/v1 ◽

2021 ◽

Author(s):

Hao Zhang ◽

Tao Liu

Keyword(s):

Immune System ◽

Network Analysis ◽

Protein Interaction ◽

Protein Interaction Network ◽

Experimental Studies ◽

Interaction Network ◽

The Body ◽

Gene Analysis ◽

Functional Enrichment ◽

Skin Immune System

Abstract Background: Herpes simplex virus type 2 infects the body and becomes an incurable and recurring disease. The pathogenesis of HSV-2 infection is not completely clear.Methods: We analyze the GSE18527 dataset in the GEO database in this paper to obtain distinctively displayed genes(DDGs)in the total sequential RNA of the biopsies of normal and lesioned skin groups, healed skin and lesioned skin groups of genital herpes patients, respectively.The related data of 3 cases of normal skin group, 4 cases of lesioned group and 6 cases of healed group were analyzed.The histospecific gene analysis , functional enrichment and protein interaction network analysis of the differential genes were also performed, and the critical components were selected.Results: 40 up-regulated genes and 43 down-regulated genes were isolated by differential performance assay.Histospecific gene analysis of DDGs suggested that the most abundant system for gene expression was the skin, immune system and the nervous system.Through the construction of core gene combinations, protein interaction network analysis and selection of histospecific distribution genes, 17 associated genes were selected：CXCL10,MX1,ISG15,IFIT1,IFIT3,IFIT2,OASL,ISG20,RSAD2,GBP1,IFI44L,DDX58,USP18,CXCL11,GBP5,GBP4 and CXCL9.The above genes are mainly located in the skin, immune system, nervous system and reproductive system.Conclusion:This paper elucidates an effective approach for a new mechanism of HSV-2 infection, and the molecular mechanism of the selected core genes in the process of HSV-2 infection requires future experimental studies.

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Identification of Age-Related Macular Degeneration Related Genes by Applying Shortest Path Algorithm in Protein-Protein Interaction Network

BioMed Research International ◽

10.1155/2013/523415 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 12

Author(s):

Jian Zhang ◽

Min Jiang ◽

Fei Yuan ◽

Kai-Yan Feng ◽

Yu-Dong Cai ◽

...

Keyword(s):

Macular Degeneration ◽

Shortest Path ◽

Protein Interaction ◽

Permutation Test ◽

Interaction Network ◽

Age Related Macular Degeneration ◽

Shortest Path Algorithm ◽

Protein Protein Interaction ◽

Age Related ◽

Protein Protein Interaction Network

This study attempted to find novel age-related macular degeneration (AMD) related genes based on 36 known AMD genes. The well-known shortest path algorithm, Dijkstra’s algorithm, was applied to find the shortest path connecting each pair of known AMD related genes in protein-protein interaction (PPI) network. The genes occurring in any shortest path were considered as candidate AMD related genes. As a result, 125 novel AMD genes were predicted. The further analysis based on betweenness and permutation test indicates that there are 10 genes involved in the formation or development of AMD and may be the actual AMD related genes with high probability. We hope that this contribution would promote the study of age-related macular degeneration and discovery of novel effective treatments.

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The molecular mechanisms associated with PIN7, a protein-protein interaction network of seven pleiotropic proteins

10.7287/peerj.preprints.27547v1 ◽

2019 ◽

Author(s):

Jarmila Nahálková

Keyword(s):

Signaling Pathway ◽

Protein Interaction ◽

Protein Interaction Network ◽

Molecular Mechanisms ◽

Interaction Network ◽

Protein Protein Interaction ◽

P53 Signaling ◽

Age Related ◽

P53 Signaling Pathway ◽

Protein Protein Interaction Network

The protein-protein interaction network of seven pleiotropic proteins (PIN7) contains proteins with multiple functions in the aging and age-related diseases (TPPII, CDK2, MYBBP1A, p53, SIRT6, SIRT7, and BSG). At the present work, the pathway enrichment, the gene function prediction and the protein node prioritization analysis were applied for the examination of main molecular mechanisms driving PIN7 and the extended network. Seven proteins of PIN7 were used as an input for the analysis by GeneMania, a Cytoscape application, which constructs the protein interaction network. The software also extends it using the interactions retrieved from databases of experimental and predicted protein-protein and genetic interactions. The analysis identified the p53 signaling pathway as the most dominant mediator of PIN7. The extended PIN7 was also analyzed by Cytohubba application, which showed that the top-ranked protein nodes belong to the group of histone acetyltransferases and histone deacetylases. These enzymes are involved in the reverse epigenetic regulation mechanisms linked to the regulation of PTK2, NFκB, and p53 signaling interaction subnetworks of the extended PIN7. The analysis emphasized the role of PTK2 signaling, which functions upstream of the p53 signaling pathway and its interaction network includes all members of the sirtuin family. Further, the analysis suggested the involvement of molecular mechanisms related to metastatic cancer (prostate cancer, small cell lung cancer), hemostasis, the regulation of the thyroid hormones and the cell cycle G1/S checkpoint. The additional data-mining analysis showed that the small protein interaction network MYBBP1A-p53-TPPII-SIRT6-CD147 controls Warburg effect and MYBBP1A-p53-TPPII-SIRT7-BSG influences mTOR signaling and autophagy. Further investigations of the detail mechanisms of these interaction networks would be beneficial for the development of novel treatments for aging and age-related diseases.

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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 ◽

Protein Interaction Network ◽

Curcuma Longa ◽

Interaction Network ◽

Functional Enrichment ◽

Target Proteins ◽

Protein Protein Interaction ◽

Protein Protein Interaction Network

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.

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Coordinated Assembly of theBacillus anthracisCoat and Exosporium during Bacterial Spore Outer Layer Formation

mBio ◽

10.1128/mbio.01166-18 ◽

2018 ◽

Vol 9 (6) ◽

Cited By ~ 3

Author(s):

Tyler J. Boone ◽

Michael Mallozzi ◽

Alex Nelson ◽

Brian Thompson ◽

Mark Khemmani ◽

...

Keyword(s):

Protein Interaction ◽

Outer Layer ◽

Protein Interaction Network ◽

Bacterial Species ◽

Model Organism ◽

Interaction Network ◽

Subcellular Location ◽

Content Type ◽

Outermost Layer

ABSTRACTBacterial spores produced by theBacillalesare composed of concentric shells, each of which contributes to spore function. Spores from all species possess a cortex and coat, but spores from many species possess additional outer layers. The outermost layer ofBacillus anthracisspores, the exosporium, is separated from the coat by a gap known as the interspace. Exosporium and interspace assembly remains largely mysterious. As a result, we have a poor understanding of the overarching mechanisms driving the assembly of one of the most ubiquitous cell types in nature. To elucidate the mechanisms directing exosporium assembly, we generated strains bearing mutations in candidate exosporium-controlling genes and analyzed the effect on exosporium formation. Biochemical and cell biological analyses argue that CotE directs the assembly of CotO into the spore and that CotO might be located at or close to the interior side of the cap. Taken together with data showing that CotE and CotO interact directlyin vitro, we propose a model in which CotE and CotO are important components of a protein interaction network that connects the exosporium to the forespore during cap formation and exosporium elongation. Our data also suggest that the cap interferes with coat assembly at one pole of the spore, altering the pattern of coat deposition compared to the model organismBacillus subtilis. We propose that the difference in coat assembly patterns between these two species is due to an inherent flexibility in coat assembly, which may facilitate the evolution of spore outer layer complexity.IMPORTANCEThis work dramatically improves our understanding of the assembly of the outermost layer of theB. anthracisspore, the exosporium, a layer that encases spores from many bacterial species and likely plays important roles in the spore’s interactions with the environment, including host tissues. Nonetheless, the mechanisms directing exosporium assembly into a shell surrounding the spore are still very poorly understood. In this study, we clarify these mechanisms by the identification of a novel protein interaction network that directs assembly to initiate at a specific subcellular location in the developing cell. Our results further suggest that the presence or absence of an exosporium has a major impact on the assembly of other more interior spore layers, thereby potentially explaining long-noted differences in spore assembly betweenB. anthracisand the model organismB. subtilis.

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Exploring the sirtuin functionality in aging through the human protein interaction networks

10.7287/peerj.preprints.27671v1 ◽

2019 ◽

Author(s):

Jarmila Nahálková

Keyword(s):

Signaling Pathways ◽

Protein Interaction ◽

Protein Interaction Network ◽

Interaction Network ◽

Enrichment Analysis ◽

Primary Objective ◽

Protein Interaction Data ◽

Pathway Enrichment Analysis ◽

Pathway Enrichment ◽

Age Related

The sirtuin family contains seven proteins with the functions in multiple diseases of aging, which makes them an attractive subject for the development of therapies of age-related diseases and anti-aging treatments. The primary objective of the protein-interaction network analysis presented here is to identify the signaling pathways and protein nodes driving the functions of the sirtuins. For this purpose, the protein-protein interaction data were collected from the available public databases, which fulfilled the quality threshold and included at least one member of the sirtuin family. The databases provided 66 interactions validated by several experiments, which were further processed by the bioinformatic tools connected to the integrated genomic, proteomic, and pharmacologic data. The interactions were analyzed by the pathway enrichment, the gene function prediction analysis, and the protein node prioritization by use of Cytoscape applications GeneMania and Cytohubba. The constructed sirtuin protein interaction network (SPIN) contained after the extension 98 protein nodes. TGFβ, PTK2, CARM1, Notch signaling and the pathways regulating androgen and estrogen levels, significantly scored in the pathway enrichment analysis of SPIN. The enriched signaling pathways mediating the pleiotropic effects of the sirtuin family, play the roles in several age-related diseases probably. The Cytohubba application has highlighted the function of HDAC1, EP300, SMAD4, MYC, SIN3A, RBBP4, HDAC, SIN3B, RBBP7 and SMAD3 as the high priority protein nodes driving the molecular functions of SPIN. The presented protein interaction study provide new understandings of the sirtuin functions in the longevity and diseases of aging including cancer, neurodegenerative and metabolic disorders.

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Identifying Potential Novel Pathways and Therapeutic Targets of Major Depressive Disorder with Functional Genomics

10.21203/rs.3.rs-374465/v1 ◽

2021 ◽

Author(s):

Kevin Bao

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Protein Interaction ◽

Protein Interaction Network ◽

Antidepressant Treatment ◽

Interaction Network ◽

Functional Enrichment ◽

Future Research ◽

Integrative Genomics ◽

Major Depressive

Abstract Background: Major depressive disorder (MDD) is a debilitating illness and a leading cause of disability, but its pathophysiology remains to be completely elucidated. Resistance to traditional antidepressant treatment is highly prevalent within patient populations. Ketamine, a rapid-acting antidepressant that has shown success in treating resistant patients, is hypothesized to function by modulating excitatory and inhibitory neurotransmitters. This has led to a paradigm shift from the monoaminergic hypothesis, towards a glutamate and neuroplasticity hypothesis, though this picture may still be incomplete. The purpose of this study is to identify novel systems potentially implicated in MDD and suggest potential therapeutic mechanisms.Methods: An integrative genomics and systems biology approach was used to identify genes and pathways that may be relevant to MDD. Starting with genes implicated in current, well-established paradigms, a correlation analysis was used to query publicly available microarray datasets to identify potential genes that may be relevant to MDD. Systems and pathways of interest were identified through functional enrichment. Through a manual review, genes of systems and pathways potentially relevant to MDD were used to generate a protein interaction network. Interesting genes identified from the network were functionally enriched and clustered to identify new high-level themes. Genes from the protein interaction network were then classified into sets based on different paradigms using functional annotations. Genes belonging to multiple sets – and thus being involved in multiple different paradigms relevant to MDD – were identified for future research.Results: The highest-ranked enrichment cluster contained GABAeric signaling, retrograde endocannabinoid signaling, and morphine addiction. Other interesting pathways identified were T cell receptor signaling, cocaine addiction, and nicotine addiction. Other broad themes identified in other clusters were calcium, serotonin, the immune system, TGF beta, glutamate, telomeres, the guanine nucleotide exchange factor, the extracellular matrix, and DNA regulation. Potential genes of interest are listed in Chart 3.Conclusions: Throughout the study, interesting genes, groups of genes, and systems were identified manually and systematically, some of which validate existing literature and some give possible directions for future research. Further experiments are required to confirm causal links.

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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 ◽

Protein Interaction Network ◽

Curcuma Longa ◽

Interaction Network ◽

Functional Enrichment ◽

Target Proteins ◽

Protein Protein Interaction ◽

Protein Protein Interaction Network

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.

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