• Title/Summary/Keyword: Target enrichment

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Prediction the efficacy and mechanism of action of Daehwangmokdanpitang to treat psoriasis based on network pharmacology (네트워크 약리학 기반 대황목단피탕(大黃牧丹皮湯)의 건선 조절 효능 및 작용 기전 예측)

  • Bitna Kweon;Dong-Uk Kim;Gabsik Yang; Il-Joo Jo
    • The Korea Journal of Herbology
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    • v.38 no.6
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    • pp.73-91
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    • 2023
  • Objectives : This study used a network pharmacology approach to elucidate the efficacy and molecular mechanisms of Daehwangmokdanpitang (DHMDPT) on Psoriasis. Methods : Using OASIS databases and PubChem database, compounds of DHMDPT and their target genes were collected. The putative target genes of DHMDPT and known target genes of psoriasis were compared and found the correlation. Then, the network was constructed using Cytoscape 3.10.1. The key target genes were screened by Analyzer network and their functional enrichment analysis was conducted based on the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways to predict the mechanisms. Results : The result showed that total 30 compounds and 439 related genes were gathered from DHMDPT. 264 genes were interacted with psoriasis gene set, suggesting that the effects of DHMDPT are closely related to psoriasis. Based on GO enrichment analysis and KEGG pathways, 'Binding', 'Cytokine Activity', 'Receptor Ligand Activity' 'HIF-1 signaling pathway', 'IL-17 signaling pathway', 'Toll-like receptor signaling pathway', and 'TNF signaling pathway' were predicted as functional pathways of 16 key target genes of DHMDPT on psoriasis. Among the target genes, IL6, IL1B, TNF, AKT1 showed high correlation with the results of KEGG pathways. Additionally, Emodin, Acetovanillone, Gallic acid, and Ferulic acid showed a high relevance with key genes and their mechanisms. Conclusion : Through a network pharmacological method, DHMDPT was predicted to have high relevance with psoriasis. This study could be used as a basis for studying therapeutic effects of DHMDPT on psoriasis.

MiRNA Synergistic Network Construction and Enrichment Analysis for Common Target Genes in Small-cell Lung Cancer

  • Zhang, Tie-Feng;Cheng, Ke-Wen;Shi, Wei-Yin;Zhang, Jin-Tao;Liu, Ke-Di;Xu, Shu-Guang;Chen, Ji-Quan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6375-6378
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    • 2012
  • Background: Small-cell lung cancer (also known as SCLC) is an aggressive form and untreated patients generally die within about 3 months. To obtain further insight into mechanism underlying malignancy with this cancer, an miRNA synergistic regulatory network was constructed and analyzed in the present study. Method: A miRNA microarray dataset was downloaded from the NCBI GEO database (GSE27435). A total of 546 miRNAs were identified to be expressed in SCLC cells. Then a miRNA synergistic network was constructed, and the included miRNAs mapped to the network. Topology analysis was also performed to analyze the properties of the synergistic network. Consequently, we could identified constitutive modules. Further, common target genes of each module were identified with CFinder. Finally, enrichment analysis was performed for target genes. Results: In this study, a miRNA synergistic network with 464 miRNAs and 2981 edges was constructed. According to the topology analysis, the topological properties between the networks constructed by LC related miRNAs and LC unrelated miRNAs were significantly different. Moreover, a module cilque0 could be identified in our network using CFinder. The module included three miRNAs (hsa-let-7c, hsa-let-7b and hsa-let-7d). In addition, several genes were found which were predicted to be common targets of cilque0. The enrichment analysis demonstrated that these target genes were enriched in MAPK signaling pathways. Conclusions: Although limitations exist in the current data, the results uncovered here are important for understanding the key roles of miRNAs in SCLC. However, further validation is required since our results were based on microarray data derived from a small sample size.

NGSEA: Network-Based Gene Set Enrichment Analysis for Interpreting Gene Expression Phenotypes with Functional Gene Sets

  • Han, Heonjong;Lee, Sangyoung;Lee, Insuk
    • Molecules and Cells
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    • v.42 no.8
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    • pp.579-588
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    • 2019
  • Gene set enrichment analysis (GSEA) is a popular tool to identify underlying biological processes in clinical samples using their gene expression phenotypes. GSEA measures the enrichment of annotated gene sets that represent biological processes for differentially expressed genes (DEGs) in clinical samples. GSEA may be suboptimal for functional gene sets; however, because DEGs from the expression dataset may not be functional genes per se but dysregulated genes perturbed by bona fide functional genes. To overcome this shortcoming, we developed network-based GSEA (NGSEA), which measures the enrichment score of functional gene sets using the expression difference of not only individual genes but also their neighbors in the functional network. We found that NGSEA outperformed GSEA in identifying pathway gene sets for matched gene expression phenotypes. We also observed that NGSEA substantially improved the ability to retrieve known anti-cancer drugs from patient-derived gene expression data using drug-target gene sets compared with another method, Connectivity Map. We also repurposed FDA-approved drugs using NGSEA and experimentally validated budesonide as a chemical with anti-cancer effects for colorectal cancer. We, therefore, expect that NGSEA will facilitate both pathway interpretation of gene expression phenotypes and anti-cancer drug repositioning. NGSEA is freely available at www.inetbio.org/ngsea.

Determination of Optimum Batch Size and Fuel Enrichment for OPR1000 NPP Based on Nuclear Fuel Cycle Cost Analysis (OPR1000 발전소의 핵연료 주기비분석을 통한 최적 배취 크기와 핵연료 농축도 결정)

  • Cho, Sung Ju;Hah, Chang Joo
    • Journal of Energy Engineering
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    • v.23 no.4
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    • pp.256-262
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    • 2014
  • Cycle length of domestic nuclear power plants is determined by the demand-supply plan of utility company. The target cycle length is achieved by adjusting the number of feed fuel assembly and fuel enrichment. Traditionally, utility company first select the number of feed fuel assembly and then find out the fuel enrichment to achieve the special cycle length. But it is difficult to find out if this method is most economical than any other combinations of the enrichment and batch size satisfying the same cycle length. In this paper, core depletion calculation is performed to find out the optimum combination of the enrichment and batch size for given target cycle length in terms of fuel cycle cost using commercial core design code; CASMO/MASTER code. To minimize the uncertainty resulting from transition core analysis, levelized fuel cycle cost analysis was applied to the equilibrium cycle core in order to determine the optimum combination. The sensitivity study of discount rate was also carried out to analyze the levelized fuel cycle cost applicable to countries with different discount rates. From the levelized fuel cycle cost analysis results, the combination with smaller batch size and higher fuel enrichment becomes more economical as the discount rate becomes lower. On the other hand, the combination with higher batch size and lower fuel enrichment becomes more economical as the discount rate becomes higher.

Implementation of Active Sound Enrichment Control for Improving Engine Sound Quality Inside the Cabin of a Passenger Car (차량 실내공간의 가속 시 엔진음 음질 향상을 위한 실시간 능동음향증강 제어 구현)

  • Lee, Young-Sup;Kim, Jeakwan;Ryu, Seokhoon;Kim, Seonghyeon;Park, Dong Chul
    • Transactions of the Korean Society for Noise and Vibration Engineering
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    • v.26 no.2
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    • pp.195-202
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    • 2016
  • In this study, a concept of active sound enrichment (ASE) control system was implemented and demonstrated for improving engine sound quality inside the cabin of a passenger car during acceleration. Unlike the active noise control cancels the noise for disturbance rejection, the ASE adds additional sound to the noise for tracking control. This approach requires a new algorithm to provide additional artificial sound to the original engine sound using active control strategy to achieve a target sound profile, which is predefined to satisfy required interior sound quality. The ASE algorithm was implemented in a digital controller dSPACE DS1401 and real-time control experiment was accomplished in an actual car. The ASE control results show that the actively enriched sound of each engine order against RPM tracks the target profiles precisely and quickly and improves the discontinuity, the level ratios and the sound pressure level of each engine order. Thus it is anticipated the ASE system can be applied for the improvement of the engine sound quality inside the cabin during acceleration.

Novel Discovery of LINE-1 in a Korean Individual by a Target Enrichment Method

  • Shin, Wonseok;Mun, Seyoung;Kim, Junse;Lee, Wooseok;Park, Dong-Guk;Choi, Seungkyu;Lee, Tae Yoon;Cha, Seunghee;Han, Kyudong
    • Molecules and Cells
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    • v.42 no.1
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    • pp.87-95
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    • 2019
  • Long interspersed element-1 (LINE-1 or L1) is an autonomous retrotransposon, which is capable of inserting into a new region of genome. Previous studies have reported that these elements lead to genomic variations and altered functions by affecting gene expression and genetic networks. Mounting evidence strongly indicates that genetic diseases or various cancers can occur as a result of retrotransposition events that involve L1s. Therefore, the development of methodologies to study the structural variations and interpersonal insertion polymorphisms by L1 element-associated changes in an individual genome is invaluable. In this study, we applied a systematic approach to identify human-specific L1s (i.e., L1Hs) through the bioinformatics analysis of high-throughput next-generation sequencing data. We identified 525 candidates that could be inferred to carry non-reference L1Hs in a Korean individual genome (KPGP9). Among them, we randomly selected 40 candidates and validated that approximately 92.5% of non-reference L1Hs were inserted into a KPGP9 genome. In addition, unlike conventional methods, our relatively simple and expedited approach was highly reproducible in confirming the L1 insertions. Taken together, our findings strongly support that the identification of non-reference L1Hs by our novel target enrichment method demonstrates its future application to genomic variation studies on the risk of cancer and genetic disorders.

Network Pharmacology-based Prediction of Efficacy and Mechanism of Yunpye-hwan Acting on COPD (네트워크 약리학을 이용한 윤폐환(潤肺丸)의 COPD 치료 효능 및 작용기전 연구)

  • Minju Kim;Aram Yang;Bitna Kweon;Dong-Uk Kim;Gi-Sang Bae
    • The Korea Journal of Herbology
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    • v.39 no.3
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    • pp.37-47
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    • 2024
  • Objectives : Because predicting the potential efficacy and mechanisms of Korean medicines is challenging due to their high complexity, employing an approach based on network pharmacology could be effective. In this study, network pharmacological analysis was utilized to anticipate the effects of YunPye-Hwan (YPH) in treating Chronic obstructive pulmonary disease (COPD). Methods : Compounds and their related target genes of YPH were gathered from the TCMSP and PubChem databases. These target genes of YPH were subsequently compared with gene sets associated with COPD to assess correlation. Next, core genes were identified through a two-step screening process, and finally, functional enrichment analysis of these core genes was conducted using both Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways. Results : A total of 15 compounds and 437 target genes were gathered, resulting in a network comprising 473 nodes and 14,137 edges. Among them, 276 genes overlapped with gene sets associated with COPD, indicating a significant correlation between YPH and COPD. Functional enrichment analysis of the 18 core genes revealed biological processes and pathways such as "miRNA Transcription," "Nucleic Acid-Templated Transcription," "DNA-binding Transcription Factor Activity," "MAPK signaling pathway," and "TNF signaling pathway" were implicated. Conclusion : YPH exhibited significant relevance to COPD by modulating cell proliferation, differentiation, inflammation, and cell death pathways. This study could serve as a foundational framework for further research investigating the potential use of YPH in the treatment of COPD.

Integrated bioinformatics analysis of validated and circulating miRNAs in ovarian cancer

  • Dogan, Berkcan;Gumusoglu, Ece;Ulgen, Ege;Sezerman, Osman Ugur;Gunel, Tuba
    • Genomics & Informatics
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    • v.20 no.2
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    • pp.20.1-20.13
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    • 2022
  • Recent studies have focused on the early detection of ovarian cancer (OC) using tumor materials by liquid biopsy. The mechanisms of microRNAs (miRNAs) to impact OC and signaling pathways are still unknown. This study aims to reliably perform functional analysis of previously validated circulating miRNAs' target genes by using pathfindR. Also, overall survival and pathological stage analyses were evaluated with miRNAs' target genes which are common in the The Cancer Genome Atlas and GTEx datasets. Our previous studies have validated three downregulated miRNAs (hsa-miR-885-5p, hsa-miR-1909-5p, and hsa-let7d-3p) having a diagnostic value in OC patients' sera, with high-throughput techniques. The predicted target genes of these miRNAs were retrieved from the miRDB database (v6.0). Active-subnetwork-oriented Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted by pathfindR using the target genes. Enrichment of KEGG pathways assessed by the analysis of pathfindR indicated that 24 pathways were related to the target genes. Ubiquitin-mediated proteolysis, spliceosome and Notch signaling pathway were the top three pathways with the lowest p-values (p < 0.001). Ninety-three common genes were found to be differentially expressed (p < 0.05) in the datasets. No significant genes were found to be significant in the analysis of overall survival analyses, but 24 genes were found to be significant with pathological stages analysis (p < 0.05). The findings of our study provide in-silico evidence that validated circulating miRNAs' target genes and enriched pathways are related to OC and have potential roles in theranostics applications. Further experimental investigations are required to validate our results which will ultimately provide a new perspective for translational applications in OC management.

The Robot Education Program Based on Schoolwide Enrichment Model for Elementary School Students (학교전체 심화학습 모형에 기반한 초등로봇교육 프로그램)

  • Lee, YoungJun;Seo, YoungMin
    • The Journal of Korean Association of Computer Education
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    • v.15 no.5
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    • pp.33-41
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    • 2012
  • Elementary school students should have many opportunities to find their abilities and talents. However, informatics education in Korea does not target the entire elementary school students, opportunities for informatics education are given only to some students. Unlike possibilities to find mathematics gifted students and science gifted students, opportunities to find informatics gifted students are very limited. This study aims to solve current problems through a robot education program based on SEM(Schoolwide Enrichment Model). Using modified curriculum and school enrichment cluster, robot programming education is implemented at the pilot school. The result shows that robot education program based on SEM improved creative potentials of elementary school students.

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The Early Chemical Enrichment Histories of Two Sculptor Group Dwarf Galaxies as Revealed by RR Lyrae Variables

  • Yang, Soung-Chul;Wagner-Kaiser, Rachel;Sarajedini, Ata;Kim, Sang Chul;Kyeong, Jaemann
    • The Bulletin of The Korean Astronomical Society
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    • v.39 no.1
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    • pp.39.1-39.1
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    • 2014
  • We present the results of our analysis of the RR Lyrae (RRL) variable stars detected in two transition-type dwarf galaxies (dTrans), ESO294-G010 and ESO410-G005 in the Sculptor group, which is known to be one of the closest neighboring galaxy groups to our Local Group. Using deep archival images from the Advanced Camera for Surveys (ACS) onboard the Hubble Space Telescope (HST), we have identified a sample of RR Lyrae candidates in both dTrans galaxies [219 RRab (RR0) and 13 RRc (RR1) variables in ESO294-G010; 225 RRab and 44 RRc stars in ESO410-G005]. The metallicities of the individual RRab stars are calculated via the period-amplitude-[Fe/H] relation derived by Alcock et al. This yields mean metallicities of <[Fe/H]>_{ESO294} = -1.77 +/- 0.03 and <[Fe/H]>_{ESO410} = -1.64+/- 0.03. The RRL metallicity distribution functions (MDFs) are investigated further via simple chemical evolution models; these reveal the relics of the early chemical enrichment processes for these two dTrans galaxies. In the case of both galaxies, the shapes of the RRL MDFs are well-described by pre-enrichment models. This suggests two possible channels for the early chemical evolution for these Sculptor group dTrans galaxies: 1) The ancient stellar populations of our target dwarf galaxies might have formed from the star forming gas which was already enriched through "prompt initial enrichment" or an "initial nucleosynthetic spike" from the very first massive stars, or 2) this pre-enrichment state might have been achieved by the end products from more evolved systems of their nearest neighbor, NGC 55.

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