scholarly journals Spectral analysis for gene communities in cancer cells

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Ayumi Kikkawa

Abstract We investigate gene interaction networks in various cancer cells by spectral analysis of the adjacency matrices. We observe the localization of the networks on hub genes, which have an extraordinary number of links. The eigenvector centralities take finite values only on special nodes when the hub degree exceeds the critical value $d_c \simeq 40$. The degree correlation function shows the disassortative behaviour in the large degrees, and the nodes whose degrees are $d \gtrsim 40$ have a tendency to link to small degree nodes. The communities of the gene networks centred at the hub genes are extracted based on the amount of node degree discrepancies between linked nodes. We verify the Wigner–Dyson distribution of the nearest neighbour eigenvalues spacing distribution $P(s)$ in the small degree discrepancy communities (the assortative communities), and the Poisson $P(s)$ in the communities of large degree discrepancies (the disassortative communities) including the hubs.

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Yuchen Liu ◽  
Jianfa Li ◽  
Zhicong Chen ◽  
Weiren Huang ◽  
Zhiming Cai

Natural signaling circuits could be rewired to reprogram cells with pre-determined procedures. However, it is difficult to link cellular signals at will. Here, we describe signal-connectors—a series of RNA devices—that connect one signal to another signal at the translational level. We use them to either repress or enhance the translation of target genes in response to signals. Application of these devices allows us to construct various logic gates and to incorporate feedback loops into gene networks. They have also been used to rewire a native signaling pathway and even to create novel pathways. Furthermore, logical AND gates based on these devices and integration of multiple signals have been used successfully for identification and redirection of the state of cancer cells. Eventually, the malignant phenotypes of cancers have been reversed by rewiring the oncogenic signaling from promoting to suppressing tumorigenesis. We provide a novel platform for redirecting cellular information.


mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Sriparna Mukherjee ◽  
Irshad Akbar ◽  
Reshma Bhagat ◽  
Bibhabasu Hazra ◽  
Arindam Bhattacharyya ◽  
...  

ABSTRACT RNA viruses are known to modulate host microRNA (miRNA) machinery for their own benefit. Japanese encephalitis virus (JEV), a neurotropic RNA virus, has been reported to manipulate several miRNAs in neurons or microglia. However, no report indicates a complete sketch of the miRNA profile of neural stem/progenitor cells (NSPCs), hence the focus of our current study. We used an miRNA array of 84 miRNAs in uninfected and JEV-infected human neuronal progenitor cells and primary neural precursor cells isolated from aborted fetuses. Severalfold downregulation of hsa-miR-9-5p, hsa-miR-22-3p, hsa-miR-124-3p, and hsa-miR-132-3p was found postinfection in both of the cell types compared to the uninfected cells. Subsequently, we screened for the target genes of these miRNAs and looked for the biological pathways that were significantly regulated by the genes. The target genes involved in two or more pathways were sorted out. Protein-protein interaction (PPI) networks of the miRNA target genes were formed based on their interaction patterns. A binary adjacency matrix for each gene network was prepared. Different modules or communities were identified in those networks by community detection algorithms. Mathematically, we identified the hub genes by analyzing their degree centrality and participation coefficient in the network. The hub genes were classified as either provincial (P < 0.4) or connector (P > 0.4) hubs. We validated the expression of hub genes in both cell line and primary cells through qRT-PCR after JEV infection and respective miR mimic transfection. Taken together, our findings highlight the importance of specific target gene networks of miRNAs affected by JEV infection in NSPCs. IMPORTANCE JEV damages the neural stem/progenitor cell population of the mammalian brain. However, JEV-induced alteration in the miRNA expression pattern of the cell population remains an open question, hence warranting our present study. In this study, we specifically address the downregulation of four miRNAs, and we prepared a protein-protein interaction network of miRNA target genes. We identified two types of hub genes in the PPI network, namely, connector hubs and provincial hubs. These two types of miRNA target hub genes critically influence the participation strength in the networks and thereby significantly impact up- and downregulation in several key biological pathways. Computational analysis of the PPI networks identifies key protein interactions and hubs in those modules, which opens up the possibility of precise identification and classification of host factors for viral infection in NSPCs.


2022 ◽  
Author(s):  
Hanxiang Chen ◽  
Yongqing Li ◽  
Shaoming Zhang ◽  
Yunshan Wang ◽  
Lili Wang ◽  
...  

Abstract Background As one of the most common cancer among women worldwide, the prognosis of patients with advanced cervical cancer remains unsatisfactory. A study indicated that transmembrane protein 33 (TMEM33) was implicated in tumor recurrence, while its role in cervical cancer has not been elucidated. Methods TMEM33 expression in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) was primarily screened in The Cancer Genome Altas (TCGA), and further validated in Gene Expression Omnibus (GEO) database. The Kaplan–Meier plotter analysis and Cox regression were constructed to evaluate the prognostic value of TMEM33 in CESC. Functional enrichment analysis was performed with GO, KEGG and GSEA tools. Protein-protein interaction analysis and correlated gene networks were conducted using STING and GEPIA2 websites, respectively. The expression of TMEM33 in cervical cancer cells were examined by immunoblotting and RT-qPCR. Finally, CCK-8 assay and colony formation assay were performed to investigate the role of TMEM33 in cervical cancer cell proliferation. Results TMEM33 expression was significantly elevated in CESC compared with normal tissues. High expression of TMEM33 was associated with poor prognostic clinical characteristics in CESC patients. KM-plotter analysis revealed that patients with increased TMEM33 had shorter overall survival (OS), progress free interval (PFI), and disease specific survival (DSS). Moreover, Multivariate Cox analysis further confirmed that high TMEM33 expression was an independent risk factor for OS in patients with CESC. TMEM33 was associated with immune cell infiltration, and its expression was correlated with tumorigenesis-related genes RNF4, OCIAD1, TMED5, DHX15, MED28 and LETM1. More importantly, knockdown of TMEM33 in cervical cancer cells decreased the expression of those genes and inhibited cell proliferation. Conclusions Increased TMEM33 in cervical cancer can serve as an independent prognostic marker and might play a role in tumorigenesis by promoting cell proliferation.


Author(s):  
Sheila V. Stager ◽  
Simran Gupta ◽  
Richard Amdur ◽  
Steven A. Bielamowicz

Purpose The purpose of this study was to use objective measures of glottal gap, bowing, and supraglottic compression from selected images of laryngoscopic examinations from adults over 60 years of age with voice complaints and signs of aging to test current hypotheses on whether degree of severity impacts treatment recommendations and potential follow-through with treatment. Method Records from 108 individuals 60 years or older with voice complaints and signs of aging were reviewed. Three objective measures (normalized glottal gap area [NGGA], total bowing index, and normalized true vocal fold width) were derived. Each measure was subsequently divided into three categories by severity: absence, small degree, or large degree. Nonparametric statistics tested associations between severity and treatment recommendations as well as potential follow-through. Results Noninvasive treatments (observation/voice therapy) were marginally associated with no glottal gap ( p = .09). More invasive treatments (injection/bilateral thyroplasty) were associated with glottal gaps being present ( p = .026), but bilateral thyroplasty recommendations were not significantly associated with the largest gaps. Treatment modalities were not characterized by specific severity categories for any of the objective measures. No significant differences were found for any of the three objective measures between those who followed through with recommended treatment and those who did not. Discussion Results demonstrated some support for current hypotheses on how degrees of severity of objective measures relate to treatment recommendations. Of the three measures, NGGA appears to be more informative regarding treatment recommendations and follow-through, but due to low power, larger sample sizes are needed to confirm clinical relevance.


2016 ◽  
Vol 21 (1) ◽  
pp. 47
Author(s):  
Djoko Purwanto ◽  
EPF Eko Yulipriyono

The traffic problems in a big city such as Semarang generally caused by the typical situation like overcrowding at peak hours. To overcome this problem, Semarang Government has implemented “One Way System” on the Indraprasta Street section without providing road partner. This study is intended to identify the effectiveness of this policy. The following streets were reviewed: Indraprasta, Imam Bonjol, Mgr. Soegiyopranoto, and Pierre Tendean. Further, the intersections which studied are Indraprasta-Imam Bonjol-Pierre Tendean and Tugu Muda. Traffic survey data were collected in the morning and afternoon peak hours. Manual Kapasitas Jalan Indonesia 1997 was used in the data analysis procedure. This short-term study was conducted by simulating the proposed scenario and compared with the existing situations.In conclusion, “One Way System” on Indraprasta Street section is assessed not effective due to its relatively small degree of saturation, while Mgr. Soegiyopranoto Street has a large degree of saturation. Therefore, the one-way system to Imam Bonjol Street and Mgr. Soegiyopranoto Street also needed to implement and form a “rotary link“. In addition, enacting contraflow for public transport on Soegiyopranoto Street and Imam Bonjol Street is necessary, also the arrangement of signals and geometric in the intersection that linked those three streets.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Hao Yu ◽  
Yang Liu ◽  
Chao Li ◽  
Jianhao Wang ◽  
Bo Yu ◽  
...  

Background. Neuropathic pain (NP) is a devastating complication following nerve injury, and it can be alleviated by regulating neuroimmune direction. We aimed to explore the neuroimmune mechanism and identify some new diagnostic or therapeutic targets for NP treatment via bioinformatic analysis. Methods. The microarray GSE18803 was downloaded and analyzed using R. The Venn diagram was drawn to find neuroimmune-related differentially expressed genes (DEGs) in neuropathic pain. Gene Ontology (GO), pathway enrichment, and protein-protein interaction (PPI) network were used to analyze DEGs, respectively. Besides, the identified hub genes were submitted to the DGIdb database to find relevant therapeutic drugs. Results. A total of 91 neuroimmune-related DEGs were identified. The results of GO and pathway enrichment analyses were closely related to immune and inflammatory responses. PPI analysis showed two important modules and 8 hub genes: PTPRC, CD68, CTSS, RAC2, LAPTM5, FCGR3A, CD53, and HCK. The drug-hub gene interaction network was constructed by Cytoscape, and it included 24 candidate drugs and 3 hub genes. Conclusion. The present study helps us better understand the neuroimmune mechanism of neuropathic pain and provides some novel insights on NP treatment, such as modulation of microglia polarization and targeting bone resorption. Besides, CD68, CTSS, LAPTM5, FCGR3A, and CD53 may be used as early diagnostic biomarkers and the gene HCK can be a therapeutic target.


2017 ◽  
Vol 47 (13) ◽  
pp. 1445-1458 ◽  
Author(s):  
Kikuko Hotta ◽  
Masataka Kikuchi ◽  
Takuya Kitamoto ◽  
Aya Kitamoto ◽  
Yuji Ogawa ◽  
...  

2021 ◽  
Author(s):  
Gholamreza Jafari ◽  
Nastaran Allahyari ◽  
Amir Kargaran ◽  
Ali Hosseiny

Despite its high and direct impact on nearly all biological processes, the underlying structure of gene-gene interaction networks is investigated so far according to pair connections. To address this, we explore the gene interaction networks of the yeast Saccharomyces cerevisiae beyond pairwise interaction using the structural balance theory (SBT). Specifically, we ask whether essential and nonessential gene interaction networks are structurally balanced. We study triadic interactions in the weighted signed undirected gene networks and observe that balanced and unbalanced triads are over and underrepresented in both networks, thus beautifully in line with the strong notion of balance. Moreover, we note that the energy distribution of triads is significantly different in both essential and nonessential networks compared with the shuffled networks. Yet, this difference is greater in the essential network regarding the frequency as well as the energy of triads. Additionally, results demonstrate that triads in the essential gene network are more interconnected through sharing common links, while in the nonessential network they tend to be isolated. Last but not least, we investigate the contribution of all-length signed walks and its impact on the degree of balance. Our findings reveal that interestingly when considering longer cycles the nonessential gene network is more balanced compared to the essential network.


2020 ◽  
Author(s):  
Umar Ahmad ◽  
De Ming Chau ◽  
Suet Lin Chia ◽  
Khatijah Yusoff ◽  
Syahril Abdullah ◽  
...  

AbstractMotivationBladder cancer cells acquire persistent infection associated with oncolytic Newcastle disease virus (NDV) in which its molecular events are still unclear. This poses a potential problem for oncolytic virus application for cancer therapy. To unravel the molecular mechanism underlying the development of NDV persistent infection in bladder cancer, we used mRNA expression profile of the persistently infected bladder cancer cells to construct PPI network.ResultsBased on path and module exploring in the PPI network, the bridges were found mainly from pathways of p53 signalling, ECM-receptor interaction, and TGF-beta signalling by the upregulated mRNAs, to the antigen processing and presentation, protein processing in endoplasmic reticulum, completement and coagulation cascades by the downregulated mRNAs in NDV persistent TCCSUPPi cells. In persistent EJ28Pi cells comparatively, connections were identified mainly from pathways of renal carcinoma, viral carcinogenesis, Ras signalling and cell cycle by the upregulated mRNAs, to the Wnt signalling, HTLV-I infection and pathways in cancer by the downregulated mRNAs. This connection was mainly dependent on of RPL8- HSPA1A/HSPA4 in TCCSUPPi cells and EP300, PTPN11, RAC1 - TP53, SP1, CCND1 and XPO1 in EJ28Pi cells. Oncomine validation showed that the top hub genes identified in the network that includes RPL8, THBS1, F2 from TCCSUPPi and TP53 and RAC1 from EJ28Pi are involved in the development and progression of bladder cancer. Protein-drug interaction network, have identified several drugs targets that could be used to disconnect the linkages between modules and prevent bladder cancer cells from acquiring NDV persistent infection. This is the first time reporting the PPI network analysis of differentially expressed mRNAs of the NDV persistently infected bladder cancer cell lines which provide an insight into screening drugs that could be used together with NDV to manage bladder cancer resistance to therapy and progression.


2021 ◽  
Author(s):  
Hong Luan ◽  
Linge Jian ◽  
Ye He ◽  
Tuo Zhang ◽  
Yanna Su ◽  
...  

Abstract Background: Skin cutaneous melanoma is a malignant and highly metastatic skin tumor, and its morbidity and mortality are still rising worldwide. However, the molecular mechanisms that promote melanoma metastasis are unclear. Methods: Two datasets (GSE15605 and GSE46517) were retrieved to identify the differentially expressed genes (DEGs), including 23 normal skin tissues (N), 77 primary melanoma tissues (T) and 85 metastatic melanoma tissues (M). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed to explore the functions of the DEGs. The protein–protein interaction (PPI) network was constructed using the STRING tool and Cytoscape software. We used the cytoHubba plugin of Cytoscape to identify the most significant hub genes by five topological analyses (Degree, Bottleneck, MCC, MNC, and EPC). Hub gene expression was validated using the UALCAN website. Clinical relevance was investigated using The Cancer Genome Atlas (TCGA) resources. Finally, we explored the association between metastasis-associated genes and immune infiltrates through the Tumor Immune Estimation Resource (TIMER) database and performed drug-gene interaction analysis using the Drug-Gene Interaction database.Results: A total of 294 specific genes were related to melanoma metastasis and were mainly involved in the positive regulation of locomotion, mitotic cell cycle process, and epithelial cell differentiation. Four hub genes (CDK1, FOXM1, KIF11, and RFC4) were identified from the cytoHubba plugin of Cytoscape. CDK1 was significantly upregulated in metastatic melanoma compared with primary melanoma, and high expression of CDK1 was positively correlated with poor prognosis. We found that CDK1 expression correlated positively with the infiltration levels of macrophage cells (Rho = -0.164, P = 2.02e-03) and neutrophil cells (Rho = 0.269, P = 2.72e-07) in SKCM metastasis. In addition, we identified that CDK1 had a close interaction with 10 antitumor drugs. Conclusions: CDK1 was identified as a hub gene involved in the progression of melanoma metastasis and may be regarded as a therapeutic target for melanoma patients to improve prognosis and prevent metastasis in the future.


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