• Title/Summary/Keyword: protein-protein interactions network

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Basic network pharmacological analysis of Salvia miltiorrhiza root for further application to an animal stroke model (단삼(丹參)을 뇌졸중 동물모델에 적용하기 위한 기초적인 네트워크 약리학 분석)

  • Choi, Myeongjin;Yang, Wonjin;Lee, Byoungho;Cho, Suin
    • Herbal Formula Science
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    • v.29 no.1
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    • pp.19-31
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    • 2021
  • Objectives : The root of Salvia miltiorrhiza, known as 'Dansam (DS, 丹參)', is used for and treating cardiovascular diseases based on its efficacy of promoting blood circulation and breaking through a blood stasis. In this study, we would like to see if DS could be effectively used for stroke from the perspective of network pharmacology. Methods : The analysis was conducted using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database to derive the main active compounds of DS and identify the mechanism of each compound acting on the human body. The networks between compounds, target protein and disease were expressed through Cytoscape. Protein-protein interaction (PPI) analysis was performed using STRING database. Results : Fifty two active compounds of DS were identified by screening the ingredients of DS through TCMSP. Based on the networks of these compounds with target protein and disease, it can be said that DS might be effective for preventing and treating stroke. PPI result showed that adrenergic receptor has many interactions among proteins, indicating its significance in stroke pathway. Conclusion : In this study, we derived target proteins and target diseases of DS that could be used in study of stroke. However, since it is uncertain if these targets can be controlled by DS extracts or not, we would like to confirm the results with further animal experiments.

StrokeBase: A Database of Cerebrovascular Disease-related Candidate Genes

  • Kim, Young-Uk;Kim, Il-Hyun;Bang, Ok-Sun;Kim, Young-Joo
    • Genomics & Informatics
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    • v.6 no.3
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    • pp.153-156
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    • 2008
  • Complex diseases such as stroke and cancer have two or more genetic loci and are affected by environmental factors that contribute to the diseases. Due to the complex characteristics of these diseases, identifying candidate genes requires a system-level analysis of the following: gene ontology, pathway, and interactions. A database and user interface, termed StrokeBase, was developed; StrokeBase provides queries that search for pathways, candidate genes, candidate SNPs, and gene networks. The database was developed by using in silico data mining of HGNC, ENSEMBL, STRING, RefSeq, UCSC, GO, HPRD, KEGG, GAD, and OMIM. Forty candidate genes that are associated with cerebrovascular disease were selected by human experts and public databases. The networked cerebrovascular disease gene maps also were developed; these maps describe genegene interactions and biological pathways. We identified 1127 genes, related indirectly to cerebrovascular disease but directly to the etiology of cerebrovascular disease. We found that a protein-protein interaction (PPI) network that was associated with cerebrovascular disease follows the power-law degree distribution that is evident in other biological networks. Not only was in silico data mining utilized, but also 250K Affymetrix SNP chips were utilized in the 320 control/disease association study to generate associated markers that were pertinent to the cerebrovascular disease as a genome-wide search. The associated genes and the genes that were retrieved from the in silico data mining system were compared and analyzed. We developed a well-curated cerebrovascular disease-associated gene network and provided bioinformatic resources to cerebrovascular disease researchers. This cerebrovascular disease network can be used as a frame of systematic genomic research, applicable to other complex diseases. Therefore, the ongoing database efficiently supports medical and genetic research in order to overcome cerebrovascular disease.

Effects of Gleditsia spina (GS) water extract on Gene Expression of Human Melanoma cells, by using Microarry technique (DNA chip을 이용한 조각자 추출물의 인간유래 악성 종양에 미치는 영향)

  • Park, Yong-Ho;Kim, Jong-Han;Park, Su-Yeon;Choi, Jeong-Hwa
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.21 no.1
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    • pp.55-69
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    • 2008
  • Objective : This study was designed to investigated effects of Gleditsia spina (GS) on human derived melanoma cells Methods : The genetic profile for the effect of medicine on human derived melanoma cells of SK-MEL-2, was measured by using microarray technique, and the functional analysis on these genes was conducted. The network of total protein interactions was measured by using cytoscape program. Results : Total 253 genes were up-regulated and 439 genes down-regulated in cells treated with GS. Genes induced or suppressed by GS were all mainly concerned with metabolic process, regulation of biological process and protein binding. Conclusion : Suggest the possibility of GS as anti-cancer drug and cosmetic agent, and also suggest that related mechanisms are involved in regulation of intra-cellular metabolism in melanoma cells.

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Target Prediction Based On PPI Network

  • Lee, Taekeon;Hwang, Youhyeon;Oh, Min;Yoon, Youngmi
    • Journal of the Korea Society of Computer and Information
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    • v.21 no.3
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    • pp.65-71
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    • 2016
  • To reduce the expenses for development a novel drug, systems biology has been studied actively. Target prediction, a part of systems biology, contributes to finding a new purpose for FDA(Food and Drug Administration) approved drugs and development novel drugs. In this paper, we propose a classification model for predicting novel target genes based on relation between target genes and disease related genes. After collecting known target genes from TTD(Therapeutic Target Database) and disease related genes from OMIM(Online Mendelian Inheritance in Man), we analyzed the effect of target genes on disease related genes based on PPI(Protein-Protein Interactions) network. We focused on the distinguishing characteristics between known target genes and random target genes, and used the characteristics as features for building a classifier. Because our model is constructed using information about only a disease and its known targets, the model can be applied to unusual diseases without similar drugs and diseases, while existing models for finding new drug-disease associations are based on drug-drug similarity and disease-disease similarity. We validated accuracy of the model using LOOCV of ten times and the AUCs were 0.74 on Alzheimer's disease and 0.71 on Breast cancer.

Reconstruction and Exploratory Analysis of mTORC1 Signaling Pathway and Its Applications to Various Diseases Using Network-Based Approach

  • Buddham, Richa;Chauhan, Sweety;Narad, Priyanka;Mathur, Puniti
    • Journal of Microbiology and Biotechnology
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    • v.32 no.3
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    • pp.365-377
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    • 2022
  • Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biological functions by transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In cancer, this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. In the present work, we congregated an electronic network of mTORC1 built on an assembly of data using natural language processing, consisting of 470 edges (activations/interactions and/or inhibitions) and 206 nodes representing genes/proteins, using the Cytoscape 3.6.0 editor and its plugins for analysis. The experimental design included the extraction of gene expression data related to five distinct types of cancers, namely, pancreatic ductal adenocarcinoma, hepatic cirrhosis, cervical cancer, glioblastoma, and anaplastic thyroid cancer from Gene Expression Omnibus (NCBI GEO) followed by pre-processing and normalization of the data using R & Bioconductor. ExprEssence plugin was used for network condensation to identify differentially expressed genes across the gene expression samples. Gene Ontology (GO) analysis was performed to find out the over-represented GO terms in the network. In addition, pathway enrichment and functional module analysis of the protein-protein interaction (PPI) network were also conducted. Our results indicated NOTCH1, NOTCH3, FLCN, SOD1, SOD2, NF1, and TLR4 as upregulated proteins in different cancer types highlighting their role in cancer progression. The MCODE analysis identified gene clusters for each cancer type with MYC, PCNA, PARP1, IDH1, FGF10, PTEN, and CCND1 as hub genes with high connectivity. MYC for cervical cancer, IDH1 for hepatic cirrhosis, MGMT for glioblastoma and CCND1 for anaplastic thyroid cancer were identified as genes with prognostic importance using survival analysis.

Crystal Structure of SAV0927 and Its Functional Implications

  • Jeong, Soyeon;Kim, Hyo Jung;Ha, Nam-Chul;Kwon, Ae-Ran
    • Journal of Microbiology and Biotechnology
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    • v.29 no.3
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    • pp.500-505
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    • 2019
  • Staphylococcus aureus is a round-shaped, gram-positive bacterium that can cause numerous infectious diseases ranging from mild infections such as skin infections and food poisoning to life-threatening infections such as sepsis, endocarditis and toxic shock syndrome. Various antibiotic-resistant strains of S. aureus have frequently emerged, threatening human lives significantly. Despite much research on the genetics of S. aureus, many of its genes remain unknown functionally and structurally. To counteract its toxins and to prevent the antibiotic resistance of S. aureus, our understanding of S. aureus should be increased at the proteomic scale. SAV0927 was first sequenced in an antibiotic resistant S. aureus strain. The gene is a conserved hypothetical protein, and its homologues appear to be restricted to Firmicutes. In this study, we determined the crystal structure of SAV0927 at $2.5{\AA}$ resolution. The protein was primarily dimeric both in solution and in the crystals. The asymmetric unit contained five dimers that are stacked linearly with ${\sim}80^{\circ}$ rotation by each dimer, and these interactions further continued in the crystal packing, resulting in a long linear polymer. The crystal structures, together with the network analysis, provide functional implications for the SAV0927-mediated protein network.

Genetic Regulation of Cellular Responses and Signal Targeting Pathways Invoked by an Environmental Stress (환경 스트레스에 의한 세포 내 신호의 이동 경로와 유전적 조절)

  • Kim, Il-Sup;Kim, Hyun-Young;Kang, Hong-Gyu;Yoon, Ho-Sung
    • Korean Journal of Environmental Biology
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    • v.26 no.4
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    • pp.377-384
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    • 2008
  • A cell is the product of a long period of evolution and can be represented as an optimized system (homeostasis). Stimuli from the outside environment are received by sensory apparatus on the surface of the cell and transferred through complicated pathways and eventually regulate gene expression. These signals affect cell physiology, growth, and development, and the interaction among genes in the signal transduction pathway is a critical part of the regulation. In this study, the interactions of deletion mutants and overexpression of the extracopies of the genes were used to understand their relationships to each other. Also, green fluorescent protein (GFP reporter gene) was fused to the regulatory genes to elucidate their interactions. Cooverexpression of the two genes in extracopy plasmids suggested that patS acts at the downstream of hetR in the regulatory network. The experiments using gfp fusion in different genetic background cells also indicated the epistasis relationships between the two genes. A model describing the regulatory network that controls cell development is presented.

Identifying Post-translational Modification Crosstalks for Breast Cancer

  • Tung, Chi-Hua;Shueng, Pei-Wei;Chu, Yen-Wei;Chu, Yen-Wei;Chen, Chian-Ying
    • Journal of Computing Science and Engineering
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    • v.11 no.4
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    • pp.111-120
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    • 2017
  • Post-translational modifications (PTMs) of proteins play substantial roles in the gene regulation of cell physiological functions and in the generation of major diseases. However, the majority of existing studies only explored a certain PTM of proteins, while very few have investigated the PTMs of two or more domains and the effects of their interactions. In this study, after collecting data regarding a large number of breast cancer-related and validated PTMs, a sequence and domain analysis of breast cancer proteins was carried out using bioinformatics methods. Then, protein-protein interaction network-related tools were applied in order to determine the crosstalks between the PTMs of the proteins. Finally, statistical and functional analyses were conducted to identify more modification sites of domains and proteins that may interact with at least two or more PTMs. In addition to exploring the associations between the interactive effects of PTMs, the present study also provides important information that would allow biologists to further explore the regulatory pathways of biological functions and related diseases.

Studies on the Processing Properties and Interactions Between Porcine Blood Proteins and Waxy Rice Starch During Making Porcine Blood Cake

  • Lin, Chin-Wen;Yang, Jeng-Huh;Chu, Hsien-Pin;Su, Ho-Ping;Chen, Hsiao-Ling;Huang, Chia-Cheong
    • Asian-Australasian Journal of Animal Sciences
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    • v.14 no.3
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    • pp.358-364
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    • 2001
  • The physiochemical properties and interactions between porcine blood and waxy rice were determined. Addition of calcium chloride (0.15%) improved acceptability of blood cake and increased the gelatinization degree of waxy rice. The water-holding capacity of porcine blood gel (blood/water=60/40, v/v), extent of absorption and gelatinization of waxy rice, and scanning electron microscopy showed that blood protein matrix and waxy rice are competitors for holding water in the cooking procedure. Non-haem iron content increased linearly (R=0.95) when heating temperature rose. The presence of blood proteins caused increasing of peak temperature (Tp) of gelatinization in differential scanning calorimetric thermal gram, The microstnlcture of plasma proteins and haemoglobin appeared continuous changes, and interacted with surface of waxy rice flour in terms of network and mosaic form, respectively. The electrophoretic patterns revealed an interaction between plasma proteins and waxy rice glutelin and haemoglobin when heated could be found at temperatures above $60^{\circ}C$.

CONVIRT: A web-based tool for transcriptional regulatory site identification using a conserved virtual chromosome

  • Ryu, Tae-Woo;Lee, Se-Joon;Hur, Cheol-Goo;Lee, Do-Heon
    • BMB Reports
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    • v.42 no.12
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    • pp.823-828
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    • 2009
  • Techniques for analyzing protein-DNA interactions on a genome-wide scale have recently established regulatory roles for distal enhancers. However, the large sizes of higher eukaryotic genomes have made identification of these elements difficult. Information regarding sequence conservation, exon annotation and repetitive regions can be used to reduce the size of the search region. However, previously developed resources are inadequate for consolidating such information. CONVIRT is a web resource for the identification of transcription factor binding sites and also features comparative genomics. Genomic information on ortholog-independent conserved regions, exons, repeats and sequences is integrated into the virtual chromosome, and statistically over-represented single or combinations of transcription factor binding sites are sought. CONVIRT provides regulatory network analysis for several organisms with long promoter regions and permits inter-species genome alignments. CONVIRT is freely available at http://biosoft.kaist.ac.kr/convirt.