scholarly journals Protein–Protein Interaction Network Analysis Reveals Several Diseases Highly Associated with Polycystic Ovarian Syndrome

2019 ◽  
Vol 20 (12) ◽  
pp. 2959 ◽  
Author(s):  
Balqis Ramly ◽  
Nor Afiqah-Aleng ◽  
Zeti-Azura Mohamed-Hussein

Based on clinical observations, women with polycystic ovarian syndrome (PCOS) are prone to developing several other diseases, such as metabolic and cardiovascular diseases. However, the molecular association between PCOS and these diseases remains poorly understood. Recent studies showed that the information from protein–protein interaction (PPI) network analysis are useful in understanding the disease association in detail. This study utilized this approach to deepen the knowledge on the association between PCOS and other diseases. A PPI network for PCOS was constructed using PCOS-related proteins (PCOSrp) obtained from PCOSBase. MCODE was used to identify highly connected regions in the PCOS network, known as subnetworks. These subnetworks represent protein families, where their molecular information is used to explain the association between PCOS and other diseases. Fisher’s exact test and comorbidity data were used to identify PCOS–disease subnetworks. Pathway enrichment analysis was performed on the PCOS–disease subnetworks to identify significant pathways that are highly involved in the PCOS–disease associations. Migraine, schizophrenia, depressive disorder, obesity, and hypertension, along with twelve other diseases, were identified to be highly associated with PCOS. The identification of significant pathways, such as ribosome biogenesis, antigen processing and presentation, and mitophagy, suggest their involvement in the association between PCOS and migraine, schizophrenia, and hypertension.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Suthanthiram Backiyarani ◽  
Rajendran Sasikala ◽  
Simeon Sharmiladevi ◽  
Subbaraya Uma

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.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Masoumeh Adhami ◽  
Balal Sadeghi ◽  
Ali Rezapour ◽  
Ali Akbar Haghdoost ◽  
Habib MotieGhader

Abstract Background The coronavirus disease-19 (COVID-19) emerged in Wuhan, China and rapidly spread worldwide. Researchers are trying to find a way to treat this disease as soon as possible. The present study aimed to identify the genes involved in COVID-19 and find a new drug target therapy. Currently, there are no effective drugs targeting SARS-CoV-2, and meanwhile, drug discovery approaches are time-consuming and costly. To address this challenge, this study utilized a network-based drug repurposing strategy to rapidly identify potential drugs targeting SARS-CoV-2. To this end, seven potential drugs were proposed for COVID-19 treatment using protein-protein interaction (PPI) network analysis. First, 524 proteins in humans that have interaction with the SARS-CoV-2 virus were collected, and then the PPI network was reconstructed for these collected proteins. Next, the target miRNAs of the mentioned module genes were separately obtained from the miRWalk 2.0 database because of the important role of miRNAs in biological processes and were reported as an important clue for future analysis. Finally, the list of the drugs targeting module genes was obtained from the DGIDb database, and the drug-gene network was separately reconstructed for the obtained protein modules. Results Based on the network analysis of the PPI network, seven clusters of proteins were specified as the complexes of proteins which are more associated with the SARS-CoV-2 virus. Moreover, seven therapeutic candidate drugs were identified to control gene regulation in COVID-19. PACLITAXEL, as the most potent therapeutic candidate drug and previously mentioned as a therapy for COVID-19, had four gene targets in two different modules. The other six candidate drugs, namely, BORTEZOMIB, CARBOPLATIN, CRIZOTINIB, CYTARABINE, DAUNORUBICIN, and VORINOSTAT, some of which were previously discovered to be efficient against COVID-19, had three gene targets in different modules. Eventually, CARBOPLATIN, CRIZOTINIB, and CYTARABINE drugs were found as novel potential drugs to be investigated as a therapy for COVID-19. Conclusions Our computational strategy for predicting repurposable candidate drugs against COVID-19 provides efficacious and rapid results for therapeutic purposes. However, further experimental analysis and testing such as clinical applicability, toxicity, and experimental validations are required to reach a more accurate and improved treatment. Our proposed complexes of proteins and associated miRNAs, along with discovered candidate drugs might be a starting point for further analysis by other researchers in this urgency of the COVID-19 pandemic.


2021 ◽  
Author(s):  
Backiyarani Suthanthiram ◽  
Sasikala Rajendran ◽  
Sharmiladevi Simeon ◽  
Uma Subbaraya

Abstract Banana, one of the most important staple, delicious 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 exploring the PPI of candidate genes from the putative network, we postulated a putative pathway that bring insights into the significance of cytokinin mediated CLV-WUSHEL signaling pathway in addition to gibberellin mediated auxin signaling pathway in parthenocarpy. Further validation of candidate genes in seeded and seedless accession of Musa spp using qRT-PCR put forward AGL8, MADS16, IAA (GH3.8), RGA1, EXPA1, GID1C, HK2 and BAM1 as possible target genes in natural parthenocarpy. In contrary, expression profile of ACLB-2 and ZEP is anticipated to highlight the difference in artificially induced and natural 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 protein-protein interaction network.


2019 ◽  
Vol 19 (2) ◽  
pp. 146-155 ◽  
Author(s):  
Renu Chaudhary ◽  
Meenakshi Balhara ◽  
Deepak Kumar Jangir ◽  
Mehak Dangi ◽  
Mrridula Dangi ◽  
...  

<P>Background: Protein-Protein interaction (PPI) network analysis of virulence proteins of Aspergillus fumigatus is a prevailing strategy to understand the mechanism behind the virulence of A. fumigatus. The identification of major hub proteins and targeting the hub protein as a new antifungal drug target will help in treating the invasive aspergillosis. </P><P> Materials & Method: In the present study, the PPI network of 96 virulence (drug target) proteins of A. fumigatus were investigated which resulted in 103 nodes and 430 edges. Topological enrichment analysis of the PPI network was also carried out by using STRING database and Network analyzer a cytoscape plugin app. The key enriched KEGG pathway and protein domains were analyzed by STRING.Conclusion:Manual curation of PPI data identified three proteins (PyrABCN-43, AroM-34, and Glt1- 34) of A. fumigatus possessing the highest interacting partners. Top 10% hub proteins were also identified from the network using cytohubba on the basis of seven algorithms, i.e. betweenness, radiality, closeness, degree, bottleneck, MCC and EPC. Homology model and the active pocket of top three hub proteins were also predicted.</P>


2017 ◽  
Vol 8 (Suppl 1) ◽  
pp. S20-S21 ◽  
Author(s):  
Akram Safaei ◽  
Mostafa Rezaei Tavirani ◽  
Mona Zamanian Azodi ◽  
Alireza Lashay ◽  
Seyed Farzad Mohammadi ◽  
...  

2014 ◽  
Vol 934 ◽  
pp. 159-164
Author(s):  
Yun Yuan Dong ◽  
Xian Chun Zhang

Protein-protein interaction (PPI) networks provide a simplified overview of the web of interactions that take place inside a cell. According to the centrality-lethality rule, hub proteins (proteins with high degree) tend to be essential in the PPI network. Moreover, there are also many low degree proteins in the PPI network, but they have different lethality. Some of them are essential proteins (essential-nonhub proteins), and the others are not (nonessential-nonhub proteins). In order to explain why nonessential-nonhub proteins don’t have essentiality, we propose a new measure n-iep (the number of essential neighbors) and compare nonessential-nonhub proteins with essential-nonhub proteins from topological, evolutionary and functional view. The comparison results show that there are statistical differences between nonessential-nonhub proteins and essential-nonhub proteins in centrality measures, clustering coefficient, evolutionary rate and the number of essential neighbors. These are reasons why nonessential-nonhub proteins don’t have lethality.


2016 ◽  
Vol 12 (1) ◽  
pp. 85-92 ◽  
Author(s):  
Xiao-Tai Huang ◽  
Yuan Zhu ◽  
Leanne Lai Hang Chan ◽  
Zhongying Zhao ◽  
Hong Yan

We construct an integrative protein–protein interaction (PPI) network in Caenorhabditis elegans, which is weighted by our proposed reliability score based on a probability graphical model (RSPGM) method.


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