• Genomics & Informatics
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• 제10권2호
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• pp.123-127
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• 2012

Gene set analysis (GSA) is useful in interpreting a genome-wide association study (GWAS) result in terms of biological mechanism. We compared the performance of two different GSA implementations that accept GWAS p-values of single nucleotide polymorphisms (SNPs) or gene-by-gene summaries thereof, GSA-SNP and i-GSEA4GWAS, under the same settings of inputs and parameters. GSA runs were made with two sets of p-values from a Korean type 2 diabetes mellitus GWAS study: 259,188 and 1,152,947 SNPs of the original and imputed genotype datasets, respectively. When Gene Ontology terms were used as gene sets, i-GSEA4GWAS produced 283 and 1,070 hits for the unimputed and imputed datasets, respectively. On the other hand, GSA-SNP reported 94 and 38 hits, respectively, for both datasets. Similar, but to a lesser degree, trends were observed with Kyoto Encyclopedia of Genes and Genomes (KEGG) gene sets as well. The huge number of hits by i-GSEA4GWAS for the imputed dataset was probably an artifact due to the scaling step in the algorithm. The decrease in hits by GSA-SNP for the imputed dataset may be due to the fact that it relies on Z-statistics, which is sensitive to variations in the background level of associations. Judicious evaluation of the GSA outcomes, perhaps based on multiple programs, is recommended.

• Journal of Periodontal and Implant Science
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• 제41권4호
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• pp.192-200
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• 2011

Purpose: The aim of this study is to compare the gene expression profile in mesenchymal stem cells derived from dental tissues and bone marrow for characterization of dental stem cells. Methods: We employed GeneChip analysis to the expression levels of approximately 32,321 kinds of transcripts in 5 samples of bone-marrow-derived mesenchymal stem cells (BMSCs) (n=1), periodontal ligament stem cells (PDLSCs) (n=2), and dental pulp stem cells (DPSCs) (n=2). Each cell was sorted by a FACS Vantage Sorter using immunocytochemical staining of the early mesenchymal stem cell surface marker STRO-1 before the microarray analysis. Results: We identified 379 up-regulated and 133 down-regulated transcripts in BMSCs, 68 up-regulated and 64 down-regulated transcripts in PDLSCs, and 218 up-regulated and 231 down-regulated transcripts in DPSCs. In addition, anatomical structure development and anatomical structure morphogenesis gene ontology (GO) terms were over-represented in all three different mesenchymal stem cells and GO terms related to blood vessels, and neurons were over-represented only in DPSCs. Conclusions: This study demonstrated the genome-wide gene expression patterns of STRO-$1^+$ mesenchymal stem cells derived from dental tissues and bone marrow. The differences among the expression profiles of BMSCs, PDLSCs, and DPSCs were shown, and 999 candidate genes were found to be definitely up- or down-regulated. In addition, GOstat analyses of regulated gene products provided over-represented GO classes. These data provide a first step for discovering molecules key to the characteristics of dental stem cells.

• Genomics & Informatics
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• 제21권3호
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• pp.36.1-36.19
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• 2023

The LIM domain-containing proteins are dominantly found in plants and play a significant role in various biological processes such as gene transcription as well as actin cytoskeletal organization. Nevertheless, genome-wide identification as well as functional analysis of the LIM gene family have not yet been reported in the economically important plant sorghum (Sorghum bicolor L.). Therefore, we conducted an in silico identification and characterization of LIM genes in S. bicolor genome using integrated bioinformatics approaches. Based on phylogenetic tree analysis and conserved domain, we identified five LIM genes in S. bicolor (SbLIM) genome corresponding to Arabidopsis LIM (AtLIM) genes. The conserved domain, motif as well as gene structure analyses of the SbLIM gene family showed the similarity within the SbLIM and AtLIM members. The gene ontology (GO) enrichment study revealed that the candidate LIM genes are directly involved in cytoskeletal organization and various other important biological as well as molecular pathways. Some important families of regulating transcription factors such as ERF, MYB, WRKY, NAC, bZIP, C2H2, Dof, and G2-like were detected by analyzing their interaction network with identified SbLIM genes. The cis-acting regulatory elements related to predicted SbLIM genes were identified as responsive to light, hormones, stress, and other functions. The present study will provide valuable useful information about LIM genes in sorghum which would pave the way for the future study of functional pathways of candidate SbLIM genes as well as their regulatory factors in wet-lab experiments.

• 한국정보과학회:학술대회논문집
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• 한국정보과학회 2002년도 가을 학술발표논문집 Vol.29 No.2 (2)
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• pp.229-231
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• 2002

생물학 분야의 방대한 지식을 효율적으로 다루기 위하여 생물정보학이 주요한 연구 분야가 되었다. 이중 특히 생물학 문헌에서 정보를 자동으로 추출하는 연구가 활발히 진행되고 있는데, 이러한 정보추출 결과를 이용하여 유전자 온톨로지와 같은 유용한 지식베이스를 자동으로 확장함으로써 폭발적으로 증가하는 생물학 분야의 연구 결과들을 지식베이스에 통합할 수 있다. 자동으로 확장된 온톨로지는 신뢰성을 보장하기 위한 검증 과정을 거쳐, 정보추출 시스템의 성능을 향상시키기 위한 지식베이스로 사용되게 된다. 본 연구에서는 단백질 간의 상호작용에서 나타나는 조건을 추출하는 시스템과 유전자 온톨로지를 이용하여 추출된 생물학 용어를 분석하는 시스템을 제안하고 유전자 온톨로지의 자동 확장 및 검증 시스템에 대하여 논의한다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6347-6350
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• 2013

Post-transplant lymphoproliferative disorder (PTLD) is a common complication of therapeutic immunosuppression after organ transplantation. Gene expression profile facilitates the identification of biological difference between Epstein-Barr virus (EBV) positive and negative PTLDs. Previous studies mainly implemented variance/regression analysis without considering unaccounted array specific factors. The aim of this study is to investigate the gene expression difference between EBV positive and negative PTLDs through partial least squares (PLS) based analysis. With a microarray data set from the Gene Expression Omnibus database, we performed PLS based analysis. We acquired 1188 differentially expressed genes. Pathway and Gene Ontology enrichment analysis identified significantly over-representation of dysregulated genes in immune response and cancer related biological processes. Network analysis identified three hub genes with degrees higher than 15, including CREBBP, ATXN1, and PML. Proteins encoded by CREBBP and PML have been reported to be interact with EBV before. Our findings shed light on expression distinction of EBV positive and negative PTLDs with the hope to offer theoretical support for future therapeutic study.

• Asian-Australasian Journal of Animal Sciences
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• 제30권11호
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• pp.1529-1539
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• 2017

Objective: The objective of this study was to compare the DNA methylation profile in the longissimus dorsi muscle between Small Tailed Han and Dorper${\times}$Small Tailed Han crossbred sheep which were known to exhibit significant difference in meat-production. Methods: Six samples (three in each group) were subjected to the methylated DNA immunoprecipitation sequencing (MeDIP-seq) and subsequent bioinformatics analyses to detect differentially methylated regions (DMRs) between the two groups. Results: 23.08 Gb clean data from six samples were generated and 808 DMRs were identified in gene body or their neighboring up/downstream regions. Compared with Small Tailed Han sheep, we observed a tendency toward a global loss of DNA methylation in these DMRs in the crossbred group. Gene ontology enrichment analysis found several gene sets which were hypomethylated in gene-body region, including nucleoside binding, motor activity, phospholipid binding and cell junction. Numerous genes were found to be differentially methylated between the two groups with several genes significantly differentially methylated, including transforming growth factor beta 3 (TGFB3), acyl-CoA synthetase long chain family member 1 (ACSL1), ryanodine receptor 1 (RYR1), acyl-CoA oxidase 2 (ACOX2), peroxisome proliferator activated receptor-gamma2 (PPARG2), netrin 1 (NTN1), ras and rab interactor 2 (RIN2), microtubule associated protein RP/EB family member 1 (MAPRE1), ADAM metallopeptidase with thrombospondin type 1 motif 2 (ADAMTS2), myomesin 1 (MYOM1), zinc finger, DHHC type containing 13 (ZDHHC13), and SH3 and PX domains 2B (SH3PXD2B). The real-time quantitative polymerase chain reaction validation showed that the 12 genes are differentially expressed between the two groups. Conclusion: In the current study, a tendency to a global loss of DNA methylation in these DMRs in the crossbred group was found. Twelve genes, TGFB3, ACSL1, RYR1, ACOX2, PPARG2, NTN1, RIN2, MAPRE1, ADAMTS2, MYOM1, ZDHHC13, and SH3PXD2B, were found to be differentially methylated between the two groups by gene ontology enrichment analysis. There are differences in the expression of 12 genes, of which ACSL1, RIN2, and ADAMTS2 have a negative correlation with methylation levels and the data suggest that DNA methylation levels in DMRs of the 3 genes may have an influence on the expression. These results will serve as a valuable resource for DNA methylation investigations on screening candidate genes which might be related to meat production in sheep.

• Molecules and Cells
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• 제45권5호
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• pp.306-316
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• 2022

Chronic stress contributes to the risk of developing depression; the habenula, a nucleus in epithalamus, is associated with many neuropsychiatric disorders. Using genome-wide gene expression analysis, we analyzed the transcriptome of the habenula in rats exposed to chronic restraint stress for 14 days. We identified 379 differentially expressed genes (DEGs) that were affected by chronic stress. These genes were enriched in neuroactive ligand-receptor interaction, the cAMP (cyclic adenosine monophosphate) signaling pathway, circadian entrainment, and synaptic signaling from the Kyoto Encyclopedia of Genes and Genomes pathway analysis and responded to corticosteroids, positive regulation of lipid transport, anterograde trans-synaptic signaling, and chemical synapse transmission from the Gene Ontology analysis. Based on protein-protein interaction network analysis of the DEGs, we identified neuroactive ligand-receptor interactions, circadian entrainment, and cholinergic synapse-related subclusters. Additionally, cell type and habenular regional expression of DEGs, evaluated using a recently published single-cell RNA sequencing study (GSE137478), strongly suggest that DEGs related to neuroactive ligand-receptor interaction and trans-synaptic signaling are highly enriched in medial habenular neurons. Taken together, our findings provide a valuable set of molecular targets that may play important roles in mediating the habenular response to stress and the onset of chronic stress-induced depressive behaviors.

• Asian-Australasian Journal of Animal Sciences
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• 제29권10호
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• pp.1515-1521
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• 2016

Anethole and garlic have an immune modulatory effects on avian coccidiosis, and these effects are correlated with gene expression changes in intestinal epithelial lymphocytes (IELs). In this study, we integrated gene expression datasets from two independent experiments and investigated gene expression profile changes by anethole and garlic respectively, and identified gene expression signatures, which are common targets of these herbs as they might be used for the evaluation of the effect of plant herbs on immunity toward avian coccidiosis. We identified 4,382 and 371 genes, which were differentially expressed in IELs of chickens supplemented with garlic and anethole respectively. The gene ontology (GO) term of differentially expressed genes (DEGs) from garlic treatment resulted in the biological processes (BPs) related to proteolysis, e.g., "modification-dependent protein catabolic process", "proteolysis involved in cellular protein catabolic process", "cellular protein catabolic process", "protein catabolic process", and "ubiquitin-dependent protein catabolic process". In GO analysis, one BP term, "Proteolysis", was obtained. Among DEGs, 300 genes were differentially regulated in response to both garlic and anethole, and 234 and 59 genes were either up- or down-regulated in supplementation with both herbs. Pathway analysis resulted in enrichment of the pathways related to digestion such as "Starch and sucrose metabolism" and "Insulin signaling pathway". Taken together, the results obtained in the present study could contribute to the effective development of evaluation system of plant herbs based on molecular signatures related with their immunological functions in chicken IELs.

• Molecular & Cellular Toxicology
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• 제2권4호
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• pp.273-278
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• 2006

95 squamous cell lung carcinoma samples (normal tissue: 40 samples, tumor: 55 samples) were analyzed with 8 K cDNA microarray. 1-way ANOVA test was employed to select differentially expressed genes in tumor with FDR<0.01. Among the selected 1,655 genes, final 212 genes were chosen according to the expression fold change and used for following analysis. The expression of up-regulated 64 genes was verified with Reverse Transcription PCR and 10 genes were identified as candidates for SCC markers. In our opinion, those candidates can be exploited as diagnostic or therapeutic purposes. Gene Ontology (GO) based analysis was performed using those 212 genes, and following categories were revealed as significant biological processes: Immune response (GO: 0006955), antigen processing (GO: 0030333), inflammatory response (GO: 0006954), Cell adhesion (GO: 0007155), and Epidermis differentiation (GO: 0008544). Gene set enrichment analysis (GSEA) also carried out on overall gene expression profile with 522 functional gene sets. Glycolysis, cell cycle, K-ras and amino acid biosynthesis related gene sets were most distinguished. These results are consistent with the known characteristics of SCC and may be interconnected to rapid cell proliferation. However, the unexpected results from ERK activation in squamous cell carcinoma gripped our attention, and further studies are under progress.

• The Korean Journal of Physiology and Pharmacology
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• 제23권5호
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• pp.367-379
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• 2019

Although atopic dermatitis (AD) is known to be a representative skin disorder, it also affects the systemic immune response. In a recent study, myoblasts were shown to be involved in the immune regulation, but the roles of muscle cells in AD are poorly understood. We aimed to identify the relationship between mitochondria and atopy by genome-wide analysis of skeletal muscles in mice. We induced AD-like symptoms using house dust mite (HDM) extract in NC/Nga mice. The transcriptional profiles of the untreated group and HDM-induced AD-like group were analyzed and compared using microarray, differentially expressed gene and functional pathway analyses, and protein interaction network construction. Our microarray analysis demonstrated that immune response-, calcium handling-, and mitochondrial metabolism-related genes were differentially expressed. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology pathway analyses, immune response pathways involved in cytokine interaction, nuclear factor-kappa B, and T-cell receptor signaling, calcium handling pathways, and mitochondria metabolism pathways involved in the citrate cycle were significantly upregulated. In protein interaction network analysis, chemokine family-, muscle contraction process-, and immune response-related genes were identified as hub genes with many interactions. In addition, mitochondrial pathways involved in calcium signaling, cardiac muscle contraction, tricarboxylic acid cycle, oxidation-reduction process, and calcium-mediated signaling were significantly stimulated in KEGG and Gene Ontology analyses. Our results provide a comprehensive understanding of the genome-wide transcriptional changes of HDM-induced AD-like symptoms and the indicated genes that could be used as AD clinical biomarkers.