• Molecular & Cellular Toxicology
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• 제3권3호
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• pp.208-213
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• 2007

With the help of a development and popularization of microarray technology that enable to us to simultaneously investigate the expression pattern of thousands of genes, the toxicogenomics experimenters can interpret the genome-scale interaction between genes exposed in toxicant or toxicant-related environment. The ultimate and primary goal of toxicogenomics identifies functional context among the group of genes that are differentially or similarly coexpressed under the specific toxic substance. On the other side, public reference databases with transcriptom, proteom, and biological pathway information are needed for the analysis of these complex omics data. However, due to the heterogeneous and independent nature of these databases, it is hard to individually analyze a large omics annotations and their pathway information. Fortunately, several web sites of the public database provide information linked to other. Nevertheless it involves not only approriate information but also unnecessary information to users. Therefore, the systematically integrated database that is suitable to a demand of experimenters is needed. For these reasons, we propose SOP (Search of Omics Pathway) database system which is constructed as the integrated biological database converting heterogeneous feature of public databases into combined feature. In addition, SOP offers user-friendly web interfaces which enable users to submit gene queries for biological interpretation of gene lists derived from omics experiments. Outputs of SOP web interface are supported as the omics annotation table and the visualized pathway maps of KEGG PATHWAY database. We believe that SOP will appear as a helpful tool to perform biological interpretation of genes or proteins traced to omics experiments, lead to new discoveries from their pathway analysis, and design new hypothesis for a next toxicogenomics experiments.

• Molecules and Cells
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• 제43권6호
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• pp.551-571
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• 2020

Nuclear receptor-related 1 (Nurr1) protein has been identified as an obligatory transcription factor in midbrain dopaminergic neurogenesis, but the global set of human NURR1 target genes remains unexplored. Here, we identified direct gene targets of NURR1 by analyzing genome-wide differential expression of NURR1 together with NURR1 consensus sites in three human neural stem cell (hNSC) lines. Microarray data were validated by quantitative PCR in hNSCs and mouse embryonic brains and through comparison to published human data, including genome-wide association study hits and the BioGPS gene expression atlas. Our analysis identified ~40 NURR1 direct target genes, many of them involved in essential protein modules such as synapse formation, neuronal cell migration during brain development, and cell cycle progression and DNA replication. Specifically, expression of genes related to synapse formation and neuronal cell migration correlated tightly with NURR1 expression, whereas cell cycle progression correlated negatively with it, precisely recapitulating midbrain dopaminergic development. Overall, this systematic examination of NURR1-controlled regulatory networks provides important insights into this protein's biological functions in dopamine-based neurogenesis.

• 한국정보과학회논문지:시스템및이론
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• 제33권3호
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• pp.157-165
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• 2006

세포는 환경 변화 및 자극으로부터 자신을 보호하기 위해 유전자가 발현하여 생명을 유지 시스템을 갖고 있다. 유전자의 발현은 비정상적인 상태의 세포를 환경을 조절, 변화시켜 정상으로 바꾸기 위한 기능, 발달단계에 필요한 기능 등 생명현상에 필요한 특수 역할을 수행한다. 따라서 각 유전자의 기능을 아는 것은 생물학적으로 상당히 의미 있는 일이다. 본 논문에서는 유전자 기능을 알아보기 위해 발현 패턴을 통해 같을 때, 유사한 형태 혹은 시차를 갖고 동일한 형태로 발현하는 유전자들은 같은 기능을 한다는 가정을 하였다. 이 가정에 기반하여 각 유전자들을 기능에 따라 분류하였다. (1) IFSA선형 모델을 적용하여 데이타를 잘 나타내 줄 수 있는 특징 패턴을 찾았으며 (2) 이 특징 패턴으로부터 본 논문에서 제안한 Membership Scoring Function을 이용하여 유전자를 필터링(filtering) 하였다. 이 유전자들은 기존의 ICA(Independent Component Analysis) 방법에서 보다 IFSA 방법이 더 효과적으로 각 기능에 따른 유전자 그룹을 찾아내줌을 GO(Gene Ontology)에서 확인할 수 있었다. 이는 시차 혹은 위상 변화에 상관없이 데이타를 잘 나타낼 수 있는 IFSA의 특성이, ICA보다. 생물학적인 변수를 더 고려해 줄 수 있기 때문이라고 생각된다[1]. 이 논문의 또 다른 주요 작업은 유전자의 상호작용 관계로부터 유전자 네트웍을 얻어내는 것이다. 유전자 네트웍은 같은 그룹 내에서 유전자간의 상관 계수를 구하고 가장 높은 상관도를 보이는 유전자쌍을 연결시켜 얻게되었다. 이 네트웍 역시 GO 해석에서 그 유효성을 확인하였다.를 평균 66.02에서 58.98로 줄이면서 계산시간은 평균 71ms에서 44ms 으로 빠르게 됨을 알 수 있었다.적외선 분광법을 이용한 사일리지의 화학적 조성분 함량 측정은 적은 오차 범위 내에서 신속하고 정확한 분석법이 될 수 있음을 확인 할 수 있었다. 비록 원물 생시료(IF)에 대한 직접적인 측정은 다소 예측 정확성이 떨어지지만 현장 적용성과 편리성을 높이기 위해서는 생시료의 측정시 오차를 줄일 수 있는 스펙트럼의 수처리 방법이나 산란보정 방법과 같은 데이터 처리기법에 대한 더 많은 연구가 앞으로 진행되어야 한다고 생각되어진다.상자의 50% 이상이 매일 생선 콩 및 콩제품과 채소류를 먹고 있었고, 인스턴트나 패스트푸드는 정상 체중군이 저체중군이나 과체중보다 매일 섭취하는 빈도가 낮았다(p<0.0177). 7. 가장 낮은 영양 섭취 상태를 보여준 영양소(% RDA< 75%)는 철분과 칼슘으로 조사 대상자의 3/4에 해당하는 조사 대상자가 영양 부족 상태였다. 칼슘 섭취의 경우 정상 체중군이 과체중군과 저체중군보다 섭취율이 낮았으나(p<0.0257) 철분은 군간 유의차는 없었다. 8. 칼슘의 경우 과체중군이 저체중군이나 정상 체중군에 비해 영양소 적정비율(NAR) 값이 높았으며(p<0.0257) 철분, 단백질, 비타민 $B_1$과 $B_2$, 나이아신의 경우도 통계적으로 유의하지는 않으나 과체중군이 저체중군 또는 정상 체중군의 NAR 값이 높은 경향을 보여주었다. 9가지 영양소의 NAR을 평균한 MAR 값은 군간 유의적이지는 않으나 과체중군(0.76)이 정상체중(0.73) 또는 저체중군(0.73)에 비해 높은 값은 보여주었다. 9.

• Asian Pacific Journal of Cancer Prevention
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• 제13권2호
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• pp.641-646
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• 2012

In our recent report on gene expression in gastric cancer we identified the endo-sulfatase Sulf-1 gene to be up-regulated in gastric tumors relative to apparently normal (AN), and paired normal (PN) gastric tissue samples. In the present report we investigate the protein expression levels of Sulf-1 gene in gastric tumors, AN and PN samples using tissue microarray (TMA) and immunohistochemistry. Expression data was collected from two sets of TMA's containing replicate sections of tissue samples. Scoring data from TMA set-1 revealed a significant difference in Sulf-1 immunoreactivity between tumors and "normals" (PN and AN) (p-value = 0.001928). Also, Sulf-1 expression in tumors was also significantly different from either PN (p-value = 0.019) or AN (p-value = 0.006) samples. Similar results were obtained from analysis of scoring data from the second set of arrays. Comparison of mRNA expression and protein expression in gastric tumor tissues revealed that in 6/20 (30%) tumor samples showed up-regulated protein expression concordant with over-expression of mRNA. However, a discord with mRNA being over-expressed relative to down regulated protein expression was observed in majority 14/20 (70%) of tumor samples. Our study indicates down regulation of Sulf-1 protein expression in gastric tumors relative to PN and AN samples which is discordant with mRNA over-expression seen in tumors.

• 정보과학회 논문지
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• 제45권1호
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• pp.61-68
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• 2018

암환자의 예후 예측에 기여하는 유전자를 찾는 것은 환자에게 보다 적합한 치료를 제공하기 위한 도전 과제 중 하나이다. 예후 유전자를 찾기 위해 유전자 발현 데이터를 이용한 분류 모델 개발 연구가 많이 이루어지고 있다. 하지만 암의 이질성으로 인해 예후 예측의 정확도 향상에 한계가 있다는 문제가 있다. 본 논문에서는 유방암을 비롯한 6개의 암에 대한 암환자의 마이크로어레이 데이터와 생물학적 네트워크 데이터를 이용하여 페이지랭크 알고리즘을 통해 예후 유전자들을 식별하고, K-Nearest Neighbor 알고리즘을 사용하여 암 환자의 예후를 예측하는 모델을 제안한다. 그리고 페이지랭크를 사용하기 전에 K-Means 클러스터링으로 유전자 발현 패턴이 비슷한 샘플들을 나누어 이질성을 극복하고자 한다. 본 논문에서 제안한 방법은 기존의 유전자 바이오마커를 찾는 알고리즘보다 높은 예측 정확도를 보여 주었으며, GO 검증을 통해 클러스터에 특이적인 생물학적 기능을 확인하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1477-1482
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• 2012

Squamous cell carcinoma and adenocarcinoma are the major histological types of non-small cell lung cancer. Because they differ on the basis of histopathological and clinical characteristics and their relationship with smoking, their etiologies may be different; for example, different tumor suppressor genes may be related to the genesis of each type. We used microarray data to construct three regulatory networks to identify potential genes related to lung adenocarcinoma and squamous cell carcinoma and investigated the similarity and specificity of them. In the network, some of the observed transcription factors and target genes had been previously proven to be related to lung adenocarcinoma and squamous cell carcinoma. We also found some new transcription factors and target genes related to SCC. The results demonstrated that regulatory network analysis is useful in connection analysis between lung adenocarcinoma and squamous cell carcinoma.

• The Plant Pathology Journal
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• 제29권2호
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• pp.209-220
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• 2013

Root colonization by Pseudomonas chlororaphis O6 induces systemic drought tolerance in Arabidopsis thaliana. Microarray analysis was performed using the 22,800-gene Affymetrix GeneChips to identify differentially-expressed genes from plants colonized with or without P. chlororaphis O6 under drought stressed conditions or normal growth conditions. Root colonization in plants grown under regular irrigation condition increased transcript accumulation from genes associated with defense, response to reactive oxygen species, and auxin- and jasmonic acid-responsive genes, but decreased transcription factors associated with ethylene and abscisic acid signaling. The cluster of genes involved in plant disease resistance were up-regulated, but the set of drought signaling response genes were down-regulated in the P. chlororaphis O6-colonized under drought stress plants compared to those of the drought stressed plants without bacterial treatment. Transcripts of the jasmonic acid-marker genes, VSP1 and pdf-1.2, the salicylic acid regulated gene, PR-1, and the ethylene-response gene, HEL, also were up-regulated in plants colonized by P. chlororaphis O6, but differed in their responsiveness to drought stress. These data show how gene expression in plants lacking adequate water can be remarkably influenced by microbial colonization leading to plant protection, and the activation of the plant defense signal pathway induced by root colonization of P. chlororaphis O6 might be a key element for induced systemic tolerance by microbes.

• International Journal of Oral Biology
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• 제36권4호
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• pp.179-185
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• 2011

MicroRNAs (miRNAs) are small non-coding RNAs that mediate gene expression at the post-transcriptional level by degrading or repressing targeted mRNAs. These molecules are about 21-25 nucleotides in length and exert their effects by binding to partially complementary sites in mRNAs, predominantly in the 3'-untranslated region (3'-UTR). Recent evidence has demonstrated that miRNAs can function as oncogenes or tumor suppressors through the modulation of multiple oncogenic cellular processes in cancer development, including initiation, cell proliferation, apoptosis, invasion and metastasis. In our present study, we examined the expression profile of miRNAs related to oral cancer cell growth inhibition using normal human oral keratinocytes (NHOK) and YD-38 human oral cancer cells. By miRNA microassay analysis, 40 and 31 miRNAs among the 1,769 examined were found to be up- and down-regulated in YD-38 cells compared with NHOK cells, respectively. Using qRT-PCR analysis, the expression levels of miR-30a and miR-1246 were found to be increased in YD-38 cells compared with NHOK cells, whereas miR-203 and miR-125a were observed to be decreased. Importantly, the overexpression of miR-203 and miR-125a significantly inhibited the growth of YD-38 cells. This finding and the microarray data indicate the involvement of specific miRNAs in the development and progression of oral cancer.

• Journal of Ginseng Research
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• 제45권2호
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• pp.273-286
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• 2021

Background: Prostate carcinoma is the second most common cancer among men worldwide. Developing new therapeutic approaches and diagnostic biomarkers for prostate cancer (PC) is a significant need. The Chinese herbal medicine Panax quinquefolius saponins (PQS) have been reported to show anti-tumor effects. We hypothesized that PQS exhibits anti-cancer activity in human PC cells and we aimed to search for novel biomarkers allowing early diagnosis of PC. Methods: We used the human PC cell line DU145 and the prostate epithelial cell line PNT2 to perform cell viability assays, flow cytometric analysis of the cell cycle, and FACS-based apoptosis assays. Microarray-based gene expression analysis was used to display specific gene expression patterns and to search for novel biomarkers. Western blot and quantitative real-time PCR were performed to demonstrate the expression levels of multiple cancer-related genes. Results: Our data showed that PQS inhibited the viability of DU145 cells and induced cell cycle arrest at the G1 phase. A significant decrease in DU145 cell invasion and migration were observed after 24 h treatment by PQS. PQS up-regulated the expression levels of p21, p53, TMEM79, ACOXL, ETV5, and SPINT1 while it down-regulated the expression levels of bcl2, STAT3, FANCD2, DRD2, and TMPRSS2. Conclusion: PQS promoted cells apoptosis and inhibited the proliferation of DU145 cells, which suggests that PQS may be effective for treating PC. TMEM79 and ACOXL were expressed significantly higher in PNT2 than in DU145 cells and could be novel biomarker candidates for PC diagnosis.

• IMMUNE NETWORK
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• 제11권5호
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• pp.258-267
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• 2011

Background: Current management strategies attempt to diagnose rheumatoid arthritis (RA) at an early stage. Transcription profiling is applied in the search for biomarkers for detecting early-stage disease. Even though gene profiling has been reported using several animal models of RA, most studies were performed after the development of active arthritis, and conducted only on the peripheral blood and joint. Therefore, we investigated gene expression during the initial phase of collagen-induced arthritis (CIA) before the arthritic features developed in the thymus in addition to the peripheral blood and synovium. Methods: For gene expression analysis using cDNA microarray technology, samples of thymus, blood, and synovium were collected from CIA, rats immunized only with type II collagen (Cll), rats immunized only with adjuvant, and unimmunized rats on days 4 and 9 after the first immunization. Arrays were scanned with an Illumina bead array. Results: Of the 21,910 genes in the array, 1,243 genes were differentially expressed at least 2-fold change in various organs of CIA compared to controls. Among the 1,243 genes, 8 encode T-cell receptors (TCRs), including CD3${\zeta}$, CD3${\delta}$, CD3${\varepsilon}$, CD8${\alpha}$, and CD8${\beta}$ genes, which were down-regulated in CIA. The synovium was the organ in which the genes were differentially expressed between CIA and control group, and no difference were found in the thymus and blood. Further, we determined that the differential expression was affected by adjuvant more than Cll. The differential expression of genes as revealed by real-time RT-PCR, was in agreement with the microarray data. Conclusion: This study provides evidence that the genes encoding TCRs including CD3${\zeta}$, CD3${\delta}$, CD3${\varepsilon}$, CD8${\alpha}$, and CD8${\beta}$ genes were down-regulated during the initial phase of CIA in the synovium of CIA. In addition, adjuvant played a greater role in the down-regulation of the CD3 complex compared to CII. Therefore, the down-regulation of TCR gene expression occurred dominantly by adjuvant could be involved in the pathogenesis of the early stage at CIA.