scholarly journals Identification of the Key Regulators of Spina Bifida Through Graph-Theoretical Approach

2021 ◽  
Vol 12 ◽  
Author(s):  
Naaila Tamkeen ◽  
Suliman Yousef AlOmar ◽  
Saeed Awad M. Alqahtani ◽  
Abdullah Al-jurayyan ◽  
Anam Farooqui ◽  
...  
Keyword(s):  
Spina Bifida ◽  
Experimental Validation ◽  
Hierarchical Organization ◽  
Ppi Network ◽  
Scale Free ◽  
Protein Protein Interaction ◽  
Rich Club ◽  
Spinal Cord Malformation ◽  
Graph Theoretical Approach ◽  
Multiple Etiology

Spina Bifida (SB) is a congenital spinal cord malformation. Efforts to discern the key regulators (KRs) of the SB protein-protein interaction (PPI) network are requisite for developing its successful interventions. The architecture of the SB network, constructed from 117 manually curated genes was found to self-organize into a scale-free fractal state having a weak hierarchical organization. We identified three modules/motifs consisting of ten KRs, namely, TNIP1, TNF, TRAF1, TNRC6B, KMT2C, KMT2D, NCOA3, TRDMT1, DICER1, and HDAC1. These KRs serve as the backbone of the network, they propagate signals through the different hierarchical levels of the network to conserve the network’s stability while maintaining low popularity in the network. We also observed that the SB network exhibits a rich-club organization, the formation of which is attributed to our key regulators also except for TNIP1 and TRDMT1. The KRs that were found to ally with each other and emerge in the same motif, open up a new dimension of research of studying these KRs together. Owing to the multiple etiology and mechanisms of SB, a combination of several biomarkers is expected to have higher diagnostic accuracy for SB as compared to using a single biomarker. So, if all the KRs present in a single module/motif are targetted together, they can serve as biomarkers for the diagnosis of SB. Our study puts forward some novel SB-related genes that need further experimental validation to be considered as reliable future biomarkers and therapeutic targets.

scholarly journals Methodology of predicting novel key regulators in ovarian cancer network: a network theoretical approach

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Md. Zubbair Malik ◽  
Keilash Chirom ◽  
Shahnawaz Ali ◽  
Romana Ishrat ◽  
Pallavi Somvanshi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ppi Network ◽  
Scale Free ◽  
Protein Protein Interaction ◽  
Levels Of Organization ◽  
Grassroots Level ◽  
Community Finding ◽  
Main Regulator ◽  
Cancer Network ◽  
Modular Structures

Abstract Background Identification of key regulator/s in ovarian cancer (OC) network is important for potential drug target and prevention from this cancer. This study proposes a method to identify the key regulators of this network and their importance. Methods The protein-protein interaction (PPI) network of ovarian cancer (OC) is constructed from curated 6 hundred genes from standard six important ovarian cancer databases (some of the genes are experimentally verified). We proposed a method to identify key regulators (KRs) from the complex ovarian cancer network based on the tracing of backbone hubs, which participate at all levels of organization, characterized by Newmann-Grivan community finding method. Knockout experiment, constant Potts model and survival analysis are done to characterize the importance of the key regulators in regulating the network. Results The PPI network of ovarian cancer is found to obey hierarchical scale free features organized by topology of heterogeneous modules coordinated by diverse leading hubs. The network and modular structures are devised by fractal rules with the absence of centrality-lethality rule, to enhance the efficiency of signal processing in the network and constituting loosely connected modules. Within the framework of network theory, we device a method to identify few key regulators (KRs) from a huge number of leading hubs, that are deeply rooted in the network, serve as backbones of it and key regulators from grassroots level to complete network structure. Using this method we could able to identify five key regulators, namely, AKT1, KRAS, EPCAM, CD44 and MCAM, out of which AKT1 plays central role in two ways, first it serves as main regulator of ovarian cancer network and second serves as key cross-talk agent of other key regulators, but exhibits disassortive property. The regulating capability of AKT1 is found to be highest and that of MCAM is lowest. Conclusions The popularities of these key hubs change in an unpredictable way at different levels of organization and absence of these hubs cause massive amount of wiring energy/rewiring energy that propagate over all the network. The network compactness is found to increase as one goes from top level to bottom level of the network organization.

scholarly journals TulsiPIN: an interologous protein interactome ofOcimum tenuiflorum

2019 ◽  
Author(s):  
Vikram Singh ◽  
Gagandeep Singh ◽  
Vikram Singh
Keyword(s):  
Small World ◽  
Ppi Network ◽  
Modular Architecture ◽  
High Confidence ◽  
Scale Free ◽  
Protein Protein Interaction ◽  
Topological Features ◽  
Ppi Networks ◽  
A Genome ◽  
Transcription Regulators

AbstractOcimum tenuiflorum, commonly known as holy basil or tulsi, is globally recognized for its multitude of medicinal properties. However, a comprehensive study revealing the complex interplay among its constituent proteins at subcellular level is still lacking. To bridge this gap, a genome scale interologous protein-protein interaction (PPI) network, TulsiPIN, is developed using 49 template plants. The reported network consists of 13, 660 nodes and 327, 409 binary interactions. A high confidence PPI network consisting of 7, 719 nodes having 95, 532 interactions was inferred using domain-domain interaction information along with interolog based statistics, and its reliability was further assessed using functional homogeneity and protein colocalization. 1, 625 vital proteins are predicted by statistically evaluating this high confidence TulsiPIN with two ensembles of corresponding random networks, each consisting of 10, 000 realizations of Erdős-Rényi and Barabási-Albert models. Topological features of TulsiPIN including small-world, scale-free and modular architecture are inspected and found to resemble with other plant PPI networks. Finally, numerous regulatory proteins like transcription factors, transcription regulators and protein kinases are profiled in TulsiPIN and a sub-network of proteins participating in 10 secondary metabolite biosynthetic pathways is studied. We believe, the methodology developed and insights imparted would be useful in understanding regulatory mechanisms in various plant species.

scholarly journals Exploring the mechanism of Bushenhuoxue formula acting on postmenopausal osteoporosis via network pharmacology and experimental validation

2021 ◽  
Author(s):  
Chunhai Ke ◽  
Yizhou Chen ◽  
Yi Wang ◽  
Guonong He ◽  
Hongkai Lou ◽  
...  
Keyword(s):  
Postmenopausal Osteoporosis ◽  
Experimental Validation ◽  
Animal Experiments ◽  
Network Pharmacology ◽  
Overlapping Genes ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Vegf Signaling ◽  
Endothelial Growth Factor

Abstract Background: Bushenhuoxue (BSHX) formula, a ten-compound herbal decoction, has been used to treat postmenopausal osteoporosis (PMOP) in China for decades. Our previous study also revealed the anti-PMOP effects of BSHX formula in ovariectomized (OVX) mice. However, its pharmacological mechanisms remain unknown. Methods: Network pharmacology followed by animal experiments was used to explore the action mechanism of BSHX formula. Firstly, we obtained the chemical compounds and potential targets of BSHX formula using TCMSP and TCMID databases. Simultaneously, GeneCards and DisGeNET databases were used to determine the targets in PMOP. Based on their overlapping genes between BSHX formula and PMOP, a protein-protein interaction (PPI) network was constructed for screening hub-targets. GO and KEGG enrichment analyses were further performed to identify the critical biological processes and signaling pathways. In vivo experimental study, an OVX mouse model was established to determine the anti-PMOP effects of BSHX formula via Micro-CT assay and ABH staining. The expressions of β-catenin, alkaline phosphatase (ALP), vascular endothelial growth factor (VEGF) and CD31 were detected by immunohistochemistry.Results: A total of 218 active ingredients and 274 related targets were identified in BSHX formula. After matching with 292 therapeutic targets of PMOP, 64 overlapping genes were obtained and further used to build a PPI network in which CTNNB1 and VEGFA played a central role. GO and KEGG enrichment analyses indicated that the anti-PMOP effects of BSHX formula were mainly associated with cell proliferation, angiogenesis and their regulated pathways including β-catenin signaling and VEGF signaling. In mouse experiments, we revealed that bone mass and blood vessels in the OVX mice were significantly enhanced after treated with BSHX formula for 8 weeks. Moreover, down-regulations of β-catenin, ALP, VEGF and CD31 caused by OVX surgery were significantly restored by BSHX formula.Conclusions: Through network pharmacology and an experimental validation, we have revealed that BSHX formula exerts anti-PMOP effects mainly through promoting β-catenin-mediated osteogenesis and VEGF-mediated angiogenesis. BSHX formula can be considered as a new option for the treatment of PMOP.

Protein-Protein Interaction (PPI) Network: Recent Advances in Drug Discovery

2017 ◽  
Vol 18 (1) ◽  
pp. 5-10 ◽  
Author(s):  
Alexiou Athanasios ◽  
Vairaktarakis Charalampos ◽  
Tsiamis Vasileios ◽  
Ghulam Ashraf
Keyword(s):  
Drug Discovery ◽  
Protein Interaction ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Recent Advances

scholarly journals Decoding the molecular mechanism of parthenocarpy in Musa spp. through protein–protein interaction network

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Suthanthiram Backiyarani ◽  
Rajendran Sasikala ◽  
Simeon Sharmiladevi ◽  
Subbaraya Uma
Keyword(s):  
Candidate Genes ◽  
Protein Interaction ◽  
Target Genes ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Auxin Signaling ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
The Difference

AbstractBanana, one of the most important staple fruit among global consumers is highly sterile owing to natural parthenocarpy. Identification of genetic factors responsible for parthenocarpy would facilitate the conventional breeders to improve the seeded accessions. We have constructed Protein–protein interaction (PPI) network through mining differentially expressed genes and the genes used for transgenic studies with respect to parthenocarpy. Based on the topological and pathway enrichment analysis of proteins in PPI network, 12 candidate genes were shortlisted. By further validating these candidate genes in seeded and seedless accession of Musa spp. we put forward MaAGL8, MaMADS16, MaGH3.8, MaMADS29, MaRGA1, MaEXPA1, MaGID1C, MaHK2 and MaBAM1 as possible target genes in the study of natural parthenocarpy. In contrary, expression profile of MaACLB-2 and MaZEP is anticipated to highlight the difference in artificially induced and natural parthenocarpy. By exploring the PPI of validated genes from the network, we postulated a putative pathway that bring insights into the significance of cytokinin mediated CLAVATA(CLV)–WUSHEL(WUS) signaling pathway in addition to gibberellin mediated auxin signaling in parthenocarpy. Our analysis is the first attempt to identify candidate genes and to hypothesize a putative mechanism that bridges the gaps in understanding natural parthenocarpy through PPI network.

scholarly journals Differential Expression of mRNAs in Peripheral Blood Related to Prodrome and Progression of Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Weishuang Xue ◽  
Jinwei Li ◽  
Kailei Fu ◽  
Weiyu Teng
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Peripheral Blood ◽  
Bioinformatics Analysis ◽  
Gene Expression Omnibus ◽  
Venn Diagram ◽  
Ppi Network ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Ppi Networks

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease that affects the quality of life of elderly individuals, while the pathogenesis of AD is still unclear. Based on the bioinformatics analysis of differentially expressed genes (DEGs) in peripheral blood samples, we investigated genes related to mild cognitive impairment (MCI), AD, and late-stage AD that might be used for predicting the conversions. Methods. We obtained the DEGs in MCI, AD, and advanced AD patients from the Gene Expression Omnibus (GEO) database. A Venn diagram was used to identify the intersecting genes. Gene Ontology (GO) and Kyoto Gene and Genomic Encyclopedia (KEGG) were used to analyze the functions and pathways of the intersecting genes. Protein-protein interaction (PPI) networks were constructed to visualize the network of the proteins coded by the related genes. Hub genes were selected based on the PPI network. Results. Bioinformatics analysis indicated that there were 61 DEGs in both the MCI and AD groups and 27 the same DEGs among the three groups. Using GO and KEGG analyses, we found that these genes were related to the function of mitochondria and ribosome. Hub genes were determined by bioinformatics software based on the PPI network. Conclusions. Mitochondrial and ribosomal dysfunction in peripheral blood may be early signs in AD patients and related to the disease progression. The identified hub genes may provide the possibility for predicting AD progression or be the possible targets for treatments.

The Screening and Identification of Key Biomarkers in Adrenocortical Carcinoma: Evidence from a Bioinformatics Analysis

2022 ◽  
Vol 12 (3) ◽  
pp. 523-532
Author(s):  
Xin Yan ◽  
Chunfeng Liang ◽  
Xinghuan Liang ◽  
Li Li ◽  
Zhenxing Huang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Gene Ontology ◽  
Protein Interaction ◽  
Adrenocortical Carcinoma ◽  
Gene Expression Omnibus ◽  
Heparin Binding ◽  
Ppi Network ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Upregulated Genes

<sec> <title>Objective:</title> This study aimed to identify the potential key genes associated with the progression and prognosis of adrenocortical carcinoma (ACC). </sec> <sec> <title>Methods:</title> Differentially expressed genes (DEGs) in ACC cells and normal adrenocortical cells were assessed by microarray from the Gene Expression Omnibus database. The biological functions of the classified DEGs were examined by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses and a protein–protein interaction (PPI) network was mapped using Cytoscape software. MCODE software was also used for the module analysis and then 4 algorithms of cytohubba software were used to screen hub genes. The overall survival (OS) examination of the hub genes was then performed by the ualcan online tool. </sec> <sec> <title>Results:</title> Two GSEs (GSE12368, GSE33371) were downloaded from GEO including 18 and 43 cases, respectively. One hundred and sixty-nine DEGs were identified, including 57 upregulated genes and 112 downregulated genes. The Gene Ontology (GO) analyses showed that the upregulated genes were significantly enriched in the mitotic cytokines is, nucleus and ATP binding, while the downregulated genes were involved in the positive regulation of cardiac muscle contraction, extracellular space, and heparin-binding (P < 0.05). The Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) pathway examination showed significant pathways including the cell cycle and the complement and coagulation cascades. The protein– protein interaction (PPI) network consisted of 162 nodes and 847 edges, including mitotic nuclear division, cytoplasmic, protein kinase binding, and cell cycle. All 4 identified hub genes (FOXM1, UBE2C, KIF11, and NDC80) were associated with the prognosis of adrenocortical carcinoma (ACC) by survival analysis. </sec> <sec> <title>Conclusions:</title> The present study offered insights into the molecular mechanism of adrenocortical carcinoma (ACC) that may be beneficial in further analyses. </sec>

Comparison of Computational Tools for Protein-Protein Interaction (PPI) Mapping and Analysis

2013 ◽  
Vol 63 (1) ◽  
Author(s):  
Geok Wei Leong ◽  
Sheau Chen Lee ◽  
Cher Chien Lau ◽  
Peter Klappa ◽  
Mohd Shahir Shamsir Omar
Keyword(s):  
Protein Interactions ◽  
Network Visualization ◽  
Database Integration ◽  
File Format ◽  
Output File ◽  
Ppi Network ◽  
Protein Protein Interactions ◽  
Computational Tools ◽  
Protein Protein Interaction ◽  
Visualization Tools

Several visualization tools for the mapping of protein-protein interactions have been developed in recent years. However, a systematic comparison of the virtues and limitations of different PPI visualization tools has not been carried out so far. In this study, we compare seven commonly used visualization tools, based on input and output file format, layout algorithm, database integration, Gene Ontology annotation and accessibility of each tool. The assessment was carried out based on brain disease datasets. Our suggested tools, NAViGaTOR, Cytoscape and Gephi perform competitively as PPI network visualization tools, can be a reference for future researches on PPI mapping and analysis. 

scholarly journals TripletProt: Deep Representation Learning of Proteins based on Siamese Networks

2020 ◽  
Author(s):  
Esmaeil Nourani ◽  
Ehsaneddin Asgari ◽  
Alice C. McHardy ◽  
Mohammad R.K. Mofrad
Keyword(s):  
Functional Annotation ◽  
Cellular Localization ◽  
State Of The Art ◽  
Language Model ◽  
Representation Learning ◽  
Learning Problems ◽  
Ppi Network ◽  
New Approach ◽  
Protein Protein Interaction ◽  
Siamese Networks

AbstractWe introduce TripletProt, a new approach for protein representation learning based on the Siamese neural networks. We evaluate TripletProt comprehensively in protein functional annotation tasks including sub-cellular localization (14 categories) and gene ontology prediction (more than 2000 classes), which are both challenging multi-class multi-label classification machine learning problems. We compare the performance of TripletProt with the state-of-the-art approaches including recurrent language model-based approach (i.e., UniRep), as well as protein-protein interaction (PPI) network and sequence-based method (i.e., DeepGO). Our TripletProt showed an overall improvement of F1 score in the above mentioned comprehensive functional annotation tasks, solely relying on the PPI network. TripletProt and in general Siamese Network offer great potentials for the protein informatics tasks and can be widely applied to similar tasks.

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