scholarly journals Integrated Analysis of Gene Network in Childhood Leukemia from Microarray and Pathway Databases

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Amphun Chaiboonchoe ◽  
Sandhya Samarasinghe ◽  
Don Kulasiri ◽  
Kourosh Salehi-Ashtiani
Keyword(s):  
Gene Network ◽  
Childhood Leukemia ◽  
Therapeutic Agents ◽  
Interaction Networks ◽  
Integrated Analysis ◽  
Molecular Pathways ◽  
Biological Processes ◽  
Biological Insight ◽  
Insight Into ◽  
Pathway Databases

Glucocorticoids (GCs) have been used as therapeutic agents for children with acute lymphoblastic leukaemia (ALL) for over 50 years. However, much remains to be understood about the molecular mechanism of GCs actions in ALL subtypes. In this study, we delineate differential responses of ALL subtypes, B- and T-ALL, to GCs treatment at systems level by identifying the differences among biological processes, molecular pathways, and interaction networks that emerge from the action of GCs through the use of a selected number of available bioinformatics methods and tools. We provide biological insight into GC-regulated genes, their related functions, and their networks specific to the ALL subtypes. We show that differentially expressed GC-regulated genes participate in distinct underlying biological processes affected by GCs in B-ALL and T-ALL with little to no overlap. These findings provide the opportunity towards identifying new therapeutic targets.

scholarly journals Gene-based analysis of ADHD using PASCAL: a biological insight into the novel associated genes

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Aitana Alonso-Gonzalez ◽  
Manuel Calaza ◽  
Cristina Rodriguez-Fontenla ◽  
Angel Carracedo
Keyword(s):  
Gene Network ◽  
Association Studies ◽  
Meta Analysis ◽  
Neurodevelopmental Disorder ◽  
Differentially Expressed Gene ◽  
Brain Regions ◽  
Genome Wide Association Studies ◽  
Summary Statistics ◽  
Biological Insight ◽  
Insight Into

Abstract Background Attention-Deficit Hyperactivity Disorder (ADHD) is a complex neurodevelopmental disorder (NDD) which may significantly impact on the affected individual’s life. ADHD is acknowledged to have a high heritability component (70–80%). Recently, a meta-analysis of GWAS (Genome Wide Association Studies) has demonstrated the association of several independent loci. Our main aim here, is to apply PASCAL (pathway scoring algorithm), a new gene-based analysis (GBA) method, to the summary statistics obtained in this meta-analysis. PASCAL will take into account the linkage disequilibrium (LD) across genomic regions in a different way than the most commonly employed GBA methods (MAGMA or VEGAS (Versatile Gene-based Association Study)). In addition to PASCAL analysis a gene network and an enrichment analysis for KEGG and GO terms were carried out. Moreover, GENE2FUNC tool was employed to create gene expression heatmaps and to carry out a (DEG) (Differentially Expressed Gene) analysis using GTEX v7 and BrainSpan data. Results PASCAL results have revealed the association of new loci with ADHD and it has also highlighted other genes previously reported by MAGMA analysis. PASCAL was able to discover new associations at a gene level for ADHD: FEZF1 (p-value: 2.2 × 10− 7) and FEZF1-AS1 (p-value: 4.58 × 10− 7). In addition, PASCAL has been able to highlight association of other genes that share the same LD block with some previously reported ADHD susceptibility genes. Gene network analysis has revealed several interactors with the associated ADHD genes and different GO and KEGG terms have been associated. In addition, GENE2FUNC has demonstrated the existence of several up and down regulated expression clusters when the associated genes and their interactors were considered. Conclusions PASCAL has been revealed as an efficient tool to extract additional information from previous GWAS using their summary statistics. This study has identified novel ADHD associated genes that were not previously reported when other GBA methods were employed. Moreover, a biological insight into the biological function of the ADHD associated genes across brain regions and neurodevelopmental stages is provided.

An Insight into Oligopeptide Transporter 3 (OPT3) family proteins

2020 ◽  
Vol 27 ◽  
Author(s):  
Fırat Kurt
Keyword(s):  
Stress Responses ◽  
Chelating Agent ◽  
Biological Processes ◽  
Biotic And Abiotic Stress ◽  
Oligopeptide Transporter ◽  
Binding Residues ◽  
Fe Homeostasis ◽  
Proteins Interactions ◽  
Insight Into ◽  
Selection Of

: Oligopeptide transporter 3 (OPT3) proteins are one of the subsets of OPT clade, yet little is known about these transporters. Therefore, homolog OPT3 proteins in several plant species were investigated and characterized using bioinformatical tools. Motif and co-expression analyses showed that OPT3 proteins may be involved in both biotic and abiotic stress responses as well as growth and developmental processes. AtOPT3 usually seemed to take part in Fe homeostasis whereas ZmOPT3 putatively interacted with proteins involved in various biological processes from plant defense system to stress responses. Glutathione (GSH), as a putative alternative chelating agent, was used in the AtOPT3 and ZmOPT3 docking analyses to identify their putative binding residues. The information given in this study will contribute to the understanding of OPT3 proteins’ interactions in various pathways and to the selection of potential ligands for OPT3s.

Molecular pathways of Interferon–Stimulated Gene 15: Implications in cancer

2020 ◽  
Vol 21 ◽  
Author(s):  
Angeles C. Tecalco–Cruz
Keyword(s):  
Posttranslational Modification ◽  
Human Interferon ◽  
Molecular Pathways ◽  
Biological Processes ◽  
Small Protein ◽  
Target Proteins ◽  
Central Elements ◽  
Cancer Types ◽  
Interferon Stimulated Gene 15

Abstract:: Human interferon–stimulated gene 15 (ISG15) is a 15–kDa ubiquitin–like protein that can be detected as either free ISG15 or covalently associated with its target proteins through a process termed ISGylation. Interestingly, extracellular free ISG15 has been proposed as a cytokine–like protein, whereas ISGylation is a posttranslational modification. ISG15 is a small protein with implications in some biological processes and pathologies that include cancer. This review highlights the findings of both free ISG15 and protein ISGylation involved in several molecular pathways, emerging as central elements in some cancer types.

scholarly journals Molecular Pathways Involved in the Development of Congenital Erythrocytosis

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1150
Author(s):  
Jana Tomc ◽  
Nataša Debeljak
Keyword(s):  
Signal Transduction ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Oxygen Affinity ◽  
Molecular Pathways ◽  
Disease Development ◽  
Post Translational Modifications ◽  
Hemoglobin Oxygen Affinity ◽  
Insight Into ◽  
Idiopathic Erythrocytosis

Patients with idiopathic erythrocytosis are directed to targeted genetic testing including nine genes involved in oxygen sensing pathway in kidneys, erythropoietin signal transduction in pre-erythrocytes and hemoglobin-oxygen affinity regulation in mature erythrocytes. However, in more than 60% of cases the genetic cause remains undiagnosed, suggesting that other genes and mechanisms must be involved in the disease development. This review aims to explore additional molecular mechanisms in recognized erythrocytosis pathways and propose new pathways associated with this rare hematological disorder. For this purpose, a comprehensive review of the literature was performed and different in silico tools were used. We identified genes involved in several mechanisms and molecular pathways, including mRNA transcriptional regulation, post-translational modifications, membrane transport, regulation of signal transduction, glucose metabolism and iron homeostasis, which have the potential to influence the main erythrocytosis-associated pathways. We provide valuable theoretical information for deeper insight into possible mechanisms of disease development. This information can be also helpful to improve the current diagnostic solutions for patients with idiopathic erythrocytosis.

scholarly journals Targeting the Ubiquitin Signaling Cascade in Tumor Microenvironment for Cancer Therapy

2021 ◽  
Vol 22 (2) ◽  
pp. 791
Author(s):  
Qi Liu ◽  
Bayonle Aminu ◽  
Olivia Roscow ◽  
Wei Zhang
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Therapeutic Agents ◽  
Biological Processes ◽  
Post Translational Modification ◽  
E3 Ligases ◽  
Tumor Microenvironments ◽  
Cellular Immune ◽  
Ubiquitin Conjugating Enzymes ◽  
Cellular Components

Tumor microenvironments are composed of a myriad of elements, both cellular (immune cells, cancer-associated fibroblasts, mesenchymal stem cells, etc.) and non-cellular (extracellular matrix, cytokines, growth factors, etc.), which collectively provide a permissive environment enabling tumor progression. In this review, we focused on the regulation of tumor microenvironment through ubiquitination. Ubiquitination is a reversible protein post-translational modification that regulates various key biological processes, whereby ubiquitin is attached to substrates through a catalytic cascade coordinated by multiple enzymes, including E1 ubiquitin-activating enzymes, E2 ubiquitin-conjugating enzymes and E3 ubiquitin ligases. In contrast, ubiquitin can be removed by deubiquitinases in the process of deubiquitination. Here, we discuss the roles of E3 ligases and deubiquitinases as modulators of both cellular and non-cellular components in tumor microenvironment, providing potential therapeutic targets for cancer therapy. Finally, we introduced several emerging technologies that can be utilized to develop effective therapeutic agents for targeting tumor microenvironment.

scholarly journals POS0458 IDENTIFICATION OF HUB GENES AND MOLECULAR PATHWAYS IN PATIENTS WITH RHEUMATOID ARTHRITIS BY BIOINFORMATICS ANALYSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 460.1-460
Author(s):  
L. Cheng ◽  
S. X. Zhang ◽  
S. Song ◽  
C. Zheng ◽  
X. Sun ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Signaling Pathway ◽  
Synovial Tissue ◽  
Bioinformatics Analysis ◽  
Metabolic Process ◽  
Shanxi Province ◽  
Molecular Pathways ◽  
Biological Processes ◽  
Hub Genes ◽  
Tissue Samples

Background:Rheumatoid arthritis (RA) is a chronic, inflammatory synovitis based systemic disease of unknown etiology1. The genes and pathways in the inflamed synovium of RA patients are poorly understood.Objectives:This study aims to identify differentially expressed genes (DEGs) associated with the progression of synovitis in RA using bioinformatics analysis and explore its pathogenesis2.Methods:RA expression profile microarray data GSE89408 were acquired from the public gene chip database (GEO), including 152 synovial tissue samples from RA and 28 healthy synovial tissue samples. The DEGs of RA synovial tissues were screened by adopting the R software. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Protein-protein interaction (PPI) networks were assembled with Cytoscape software.Results:A total of 654 DEGs (268 up-regulated genes and 386 down-regulated genes) were obtained by the differential analysis. The GO enrichment results showed that the up-regulated genes were significantly enriched in the biological processes of myeloid leukocyte activation, cellular response to interferon-gamma and immune response-regulating signaling pathway, and the down-regulated genes were significantly enriched in the biological processes of extracellular matrix, retinoid metabolic process and regulation of lipid metabolic process. The KEGG annotation showed the up-regulated genes mainly participated in the staphylococcus aureus infection, chemokine signaling pathway, lysosome signaling pathway and the down-regulated genes mainly participated in the PPAR signaling pathway, AMPK signaling pathway, ECM-receptor interaction and so on. The 9 hub genes (PTPRC, TLR2, tyrobp, CTSS, CCL2, CCR5, B2M, fcgr1a and PPBP) were obtained based on the String database model by using the Cytoscape software and cytoHubba plugin3.Conclusion:The findings identified the molecular mechanisms and the key hub genes of pathogenesis and progression of RA.References:[1]Xiong Y, Mi BB, Liu MF, et al. Bioinformatics Analysis and Identification of Genes and Molecular Pathways Involved in Synovial Inflammation in Rheumatoid Arthritis. Med Sci Monit 2019;25:2246-56. doi: 10.12659/MSM.915451 [published Online First: 2019/03/28][2]Mun S, Lee J, Park A, et al. Proteomics Approach for the Discovery of Rheumatoid Arthritis Biomarkers Using Mass Spectrometry. Int J Mol Sci 2019;20(18) doi: 10.3390/ijms20184368 [published Online First: 2019/09/08][3]Zhu N, Hou J, Wu Y, et al. Identification of key genes in rheumatoid arthritis and osteoarthritis based on bioinformatics analysis. Medicine (Baltimore) 2018;97(22):e10997. doi: 10.1097/MD.0000000000010997 [published Online First: 2018/06/01]Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared

G4-PROTAC: Targeted degradation of a G-quadruplex binding protein

2021 ◽  
Author(s):  
Kiran Patil ◽  
Danielle Chin ◽  
Hui Ling Seah ◽  
Qi Shi ◽  
Kah Wai Lim ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Binding Protein ◽  
Interaction Networks ◽  
Biological Processes ◽  
G Quadruplex

G-quadruplex (G4)-binding proteins regulate important biological processes, but their interaction networks are poorly understood. We report the first use of G4 as warhead of a proteolysis-targeting chimera (G4-PROTAC) for targeted...

scholarly journals PPInfer: a Bioconductor package for inferring functionally related proteins using protein interaction networks

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1969
Author(s):  
Dongmin Jung ◽  
Xijin Ge
Keyword(s):  
Protein Interaction ◽  
Protein Interaction Networks ◽  
Interaction Networks ◽  
Biological Processes ◽  
Bioconductor Package ◽  
Biological Functions ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Related Proteins

Interactions between proteins occur in many, if not most, biological processes. This fact has motivated the development of a variety of experimental methods for the identification of protein-protein interaction (PPI) networks. Leveraging PPI data available STRING database, we use network-based statistical learning methods to infer the putative functions of proteins from the known functions of neighboring proteins on a PPI network. This package identifies such proteins often involved in the same or similar biological functions. The package is freely available at the Bioconductor web site (http://bioconductor.org/packages/PPInfer/).

scholarly journals PPInfer: a Bioconductor package for inferring functionally related proteins using protein interaction networks

F1000Research ◽  
2018 ◽  
Vol 6 ◽  
pp. 1969 ◽  
Author(s):  
Dongmin Jung ◽  
Xijin Ge
Keyword(s):  
Protein Interaction ◽  
Protein Interaction Networks ◽  
Interaction Networks ◽  
Biological Processes ◽  
Bioconductor Package ◽  
Biological Functions ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Related Proteins

Interactions between proteins occur in many, if not most, biological processes. This fact has motivated the development of a variety of experimental methods for the identification of protein-protein interaction (PPI) networks. Leveraging PPI data available in the STRING database, we use a network-based statistical learning methods to infer the putative functions of proteins from the known functions of neighboring proteins on a PPI network. This package identifies such proteins often involved in the same or similar biological functions. The package is freely available at the Bioconductor web site (http://bioconductor.org/packages/PPInfer/).

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