• Molecules and Cells
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• 제38권9호
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• pp.765-772
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• 2015

Saussurea lappa has been reported to possess anti-atopic properties. In this study, we have confirmed the S. lappa's anti-atopic properties in Nc/Nga mice and investigated the candidate gene related with its properties using microarray. We determined the target gene using real time PCR in in vitro experiment. S. lappa showed the significant reduction in atoptic dermatitis (AD) score and immunoglobulin E compared with the AD induced Nc/Nga mice. In the results of microarray using back skin obtained from animals, we found that S. lappa's properties are closely associated with cytokine-cytokine receptor interaction and the JAK-STAT signaling pathway. Consistent with the microarray data, real-time RT-PCR confirmed these modulation at the mRNA level in skin tissues from S. lappa-treated mice. Among these genes, PI3Kca and $IL20R{\beta}$ were significantly downregulated by S. lappa treatment in Nc/Nga mouse model. In in vitro experiment using HaCaT cells, we found that the S. lappa components, including alantolactone, caryophyllene, costic acid, costunolide and dehydrocostus lactone significantly decreased the expression of PI3Kca but not $IL20R{\beta}$ in vitro. Therefore, our study suggests that PI3Kca-related signaling is closely related with the protective effects of S. lappa against the development of atopic-dermatitis.

• Genomics & Informatics
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• 제4권4호
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• pp.161-166
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• 2006

The establishment of DNA microarray technology has enabled high-throughput analysis and molecular profiling of various types of cancers. By using the gene expression data from microarray analysis we are able to investigate diagnostic applications at the molecular level. The most important step in the application of microarray technology to cancer diagnostics is the selection of specific markers from gene expression profiles. In order to select markers of Immortalization and transformation we used c-myc and $H-ras^{V12}$ oncogene-transfected NIH3T3 cells as our model system. We have identified 8751 differentially expressed genes in the immortalization/transformation model by multivariate permutation F-test (95% confidence, FDR<0.01). Using the support vector machine algorithm, we selected 13 discriminative genes which could be used to predict immortalization and transformation with perfect accuracy. We assayed $H-ras^{V12}$-transfected 'transformed' cells to validate our immortalization/transformation dassification system. The selected molecular markers generated valuable additional information for tumor diagnosis, prognosis and therapy development.

• Molecules and Cells
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• 제40권10호
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• pp.714-730
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• 2017

Pre-mRNA splicing further increases protein diversity acquired through evolution. The underlying driving forces for this phenomenon are unknown, especially in terms of gene expression. A rice alternatively spliced transcript detection microarray (ASDM) and RNA sequencing (RNA-Seq) were applied to differentiate the transcriptome of 4 representative organs of Oryza sativa L. cv. Ilmi: leaves, roots, 1-cm-stage panicles and young seeds at 21 days after pollination. Comparison of data obtained by microarray and RNA-Seq showed a bell-shaped distribution and a co-lineation for highly expressed genes. Transcripts were classified according to the degree of organ enrichment using a coefficient value (CV, the ratio of the standard deviation to the mean values): highly variable (CVI), variable (CVII), and constitutive (CVIII) groups. A higher index of the portion of loci with alternatively spliced transcripts in a group (IAST) value was observed for the constitutive group. Genes of the highly variable group showed the characteristics of the examined organs, and alternatively spliced transcripts tended to exhibit the same organ specificity or less organ preferences, with avoidance of 'organ distinctness'. In addition, within a locus, a tendency of higher expression was found for transcripts with a longer coding sequence (CDS), and a spliced intron was the most commonly found type of alternative splicing for an extended CDS. Thus, pre-mRNA splicing might have evolved to retain maximum functionality in terms of organ preference and multiplicity.

• 대한핵의학회지
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• 제37권1호
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• pp.43-52
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• 2003

Microarray technology allows the simultaneous analysis of gene expression patterns of thousands of genes, in a systematic fashion, under a similar set of experimental conditions, thus making the data highly comparable. In some cases arrays are used simply as a primary screen loading to downstream molecular characterization of individual gene candidates. In other cases, the goal of expression profiling is to begin to identify complex regulatory networks underlying developmental processes and disease states. Microarrays were originally used with ceil lines or other simple model systems. More recently, microarrays have been used in the analysis of more complex biological tissues including neural systems and the brain. The application of cDNA arrays in neuropsychiatry has lagged behind other fields for a number of reasons. These include a requirement for a large amount of input probe RNA In fluorescent-glass based array systems and the cellular complexity introduced by multicellular brain and neural tissues. An additional factor that impacts the general use of microarrays in neuropsychiatry is the lack of availability of sequenced clone sets from model systems. While human cDNA clones have been widely available, high qualify rat, mouse, and drosophilae, among others are just becoming widely available. A final factor in the application of cDNA microarrays in neuropsychiatry is cost of commercial arrays. As academic microarray facilitates become more commonplace custom made arrays will become more widely available at a lower cost allowing more widespread applications. in summary, microarray technology is rapidly having an impact on many areas of biomedical research. Radioisotope-nylon based microarrays offer alternatives that may in some cases be more sensitive, flexible, inexpensive, and universal as compared to other array formats, such as fluorescent-glass arrays. In some situations of limited RNA or exotic species, radioactive membrane microarrays may be the most practical experimental approach in studying psychiatric and neurodegenerative disorders, and other complex questions in the brain.

• Genomics & Informatics
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• 제9권1호
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• pp.28-36
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• 2011

Most statistical methods for finding interesting genes are focusing on the summary values with large fold-changes or large variations. Very few methods consider the probe level data. We developed a new measure to detect reliability that incorporates the probe level data. This reliability measure is useful for exploring the microarray data without ignoring the probe level data. It is easy to calculate, and it can be used for all the other statistical methods as a good guideline to find real differentially expressed genes. Instead of filtering out genes before the analysis, we use whole genes in the analysis and make decisions with new reliability measures.

• Nuclear Engineering and Technology
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• 제54권8호
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• pp.3027-3033
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• 2022

Background: In this study, various types of deep-learning models for predicting in vitro radiosensitivity from gene-expression profiling were compared. Methods: The clonogenic surviving fractions at 2 Gy from previous publications and microarray gene-expression data from the National Cancer Institute-60 cell lines were used to measure the radiosensitivity. Seven different prediction models including three distinct multi-layered perceptrons (MLP), four different convolutional neural networks (CNN) were compared. Folded cross-validation was applied to train and evaluate model performance. The criteria for correct prediction were absolute error < 0.02 or relative error < 10%. The models were compared in terms of prediction accuracy, training time per epoch, training fluctuations, and required calculation resources. Results: The strength of MLP-based models was their fast initial convergence and short training time per epoch. They represented significantly different prediction accuracy depending on the model configuration. The CNN-based models showed relatively high prediction accuracy, low training fluctuations, and a relatively small increase in the memory requirement as the model deepens. Conclusion: Our findings suggest that a CNN-based model with moderate depth would be appropriate when the prediction accuracy is important, and a shallow MLP-based model can be recommended when either the training resources or time are limited.

• 생명과학회지
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• 제22권4호
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• pp.492-498
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• 2012

파이토케미칼이 암 세포 성장에 미치는 영향을 확인하기 위하여, 대장암 세포주 HCT116에 네 종류의 파이토케미칼을 각각 25 ${\mu}M$의 농도로 처리하였다. 처리한 파이토케미칼 중 curcumin이 가장 강력하게 세포 성장을 억제하였다. 또한 curcumin은 농도의존적으로 세포 성장을 억제하였다. Curcumin에 의한 대장암 세포주 성장 저해 활성에 대한 분자생물학적 기전을 연구하기 위하여 oligo DNA microarray 실험을 수행하였다. 그 결과, 25 ${\mu}M$ curcumin 처리에 의해 2배 이상 발현이 증가된 유전자 137개, 발현이 감소된 유전자 141개를 선별하였다. 발현이 증가된 유전자 중, 세포사멸과 밀접한 관련이 있는 것으로 알려진 유전자 3개를 선택하여, RT-PCR을 통해 이들 유전자의 발현이 감소됨을 확인하였다. 처리한 파이토케미칼 중 curcumin은 가장 강력한 ATF3의 유도자였으며, 농도의존적으로 ATF3의 발현을 증가시켰다. 흥미롭게도, curcumin에 의한 성장 저해는 ATF3-siRNA에 의한 ATF3 유전자 발현감소에 의해 성장이 회복되었다. 또한, ATF3 유전자의 과대발현 후 발현이 변화되는 유전자를 선별한 결과, 세포사멸과 관련된 많은 유전자들이 증가됨을 확인하였다. 결론적으로, 대장암 세포주에서 curcumin에 의한 항 성장활성에 있어서 ATF3 유전자가 중요한 역할을 할 것으로 생각된다.

• Toxicological Research
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• 제31권2호
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• pp.173-180
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• 2015

Extract from Gryllus bimaculatus crickets inhibits oxidation at the DNA level, with reduced production of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Microarray analyses were performed with a rat 28K cDNA clone set array to identify the gene expression profiles of aged (10 months old) Wistar Kyoto rats treated for one month with 100 mg/kg G. bimaculatus ethanol extract to assess the effects. The extract produced a meaningful anti-edema effect, evident by the inhibition of creatinine phosphokinase activity. The weights of abdominal and ovarian adipose tissues were reduced and the proportion of unsaturated fatty acids in adipose tissues was increased in an extract dose-dependent manner. Compared with untreated control rats, rats treated with the extract displayed the upregulation of 1053 genes including Fas (tumor necrosis factor receptor superfamily, member 6), Amigo3 (adhesion molecule with an immunoglobulin-like domain), Reticulon 4, 3-hydroxy-3-methylglutaryl-coenzyme (Hmgcr; a reductase), related anti-fatigue (enzyme metabolism), and Rtn antioxidant, and the downregulation of 73 genes including Ugt2b (UDP glycosyltransferase 2 family), Early growth response 1, and Glycoprotein m6a. Data suggest that G. bimaculatus extract may have value in lessening the effects of aging, resulting in a differential gene expression pattern indicative of a marked stress response and lower expression of metabolic and biosynthetic genes.

• Radiation Oncology Journal
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• 제21권1호
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• pp.54-65
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• 2003

목적 : 동시에 대량으로 유전자발현 양상을 검사할 수 있는 cDNA microarray 기법을 이용하여 자궁경부암에서 특징적으로 나타나는 유전자발현 양상을 알아보고, 방사선치료 및 방사선 항암화학요법 병용치료시의 유전자발현 변화양상을 파악하고자 하였다. 대상 및 방법 :자궁경부 편평상피암으로 확진된 후 근치목적 방사선치료를 단독으로 시행한 8명과 항암화학요법을 병행한 8명에서 채취한 종양조직을 대상으로 하고, 정상 자궁경부 3례를 대조군으로 하였다 조직 생검은 치료 전과 외부 방사선치료 16.2$\~$27 Gy에 두 번하였다. 항암화학요법을 병용한 경우, 5-FU 1,000 mg/m$^{2}$을 제 1일부터 5일까지 정주하고, clsplatin 60 mg/m$^{2}$을 제 1일에 정주하였다. cDNA microarray는 종양조직에서 추출한 total RNA를 역전사(reverse transcription)방법을 이용하여 (P-33)을 표지한 cDNAS를 제작, nylon membrane에 hybridization하였다. 이후 membrane을 phosphor-imager screens에 옮겨 1$\~$5일 동안 노출시킨 후 이미지를 스캔하였다. 유전자의 발현정도는 각 스팟(spot)들의 방사능 강도로 나타나는데, 각 스팟의 픽셀(pixel)을 Arrayguage를 사용하여 산출한 후 엑셀파일로 저장하였다. 유전자의 발현정도 비교는 원 자료(original data)를 Z-변환을 통해 보정(normalized)한 후 Z-ratio값을 산출하여 시행하였다. 결과 : 대조군에 비해 자궁경부암에서 Z-ratio 2.0 이상으로 유의한 발현증가를 보인 유전자들은 integrin-linked kinase, CDC28 protein kinase 2, Spry 2, ERK 3 등 15개로 주로 세포성장과 증식, 세포주기, 신호전달 등에 관련된 유전자들이었으며, Z-ratio -2.0 이하의 유의한 발현감소는 G protein-coupled receptor kinase 6외 6개였다. 방사선 단독치료를 시행한 후 Z-ratio 2.0 이상 발현이 증가한 것은 cyclic nucleotlde gated channel외 3개의 Expressed sequence tags (EST)들이었고, Z-ratio -2.0 이하의 발현감소를 보인 것들에는 치료전 종양세포에서 발현이 증가되었던 세포성장과 증식, 세포주기, 신호전달 등에 관련된 유전자들이 포함되었다 방사선치료와 항암화학요법을 병용했을 때는 방사선 단독치료에 비하여 세포성장과 증식 및 신호전달 관련 유전자들이 상대적으로 높게 발현되었으며, 이외에도 혈관형성(angiopoietin-2), 면역반응(formyl peptide receptor-like 1), DNA 손상회복에 관련된 유전자(CAMP phosphodiesterase)의 발현은 증가되고 세포고사(death associated protein kinase)에 관련된 유전자는 발현 감소를 보였다. 결론 : 자궁경부암에서분열과 증식 및 신호전달에 관여하는 여러 종류의 유전자들 발현이 동시다발적으로 증가되어 있다는 것과 방사선치료를 시행하면 이들 유전자의 발현이 감소하여 종양세포의 분열과 증식이 저해된다는 것을 확인하였다. 방사선 단독치료와 항암화학요법 병용치료를 비교하면 그 유전자 발현양상이 다르므로 향후 이번연구에서 나타난 유전자들에 대한 추가 연구가 필요하며, 이는 개별화된 맞춤형 치료법을 개발하는데 기초자료로 사용될 수 있을 것으로 기대된다.

• 응용통계연구
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• 제23권6호
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• pp.1067-1080
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• 2010

임상시험을 위한 표본 수 산정방법에 대해 지금까지 많은 방법이 개발되었고 현재 국내외 임상시험 기관에서 이 방법들을 토대로 표본 수를 산정하고 있다. 하지만 마이크로어레이칩 을 이용한 실험에 필요한 표본 수 산정에 대한 연구는 아직 미비하여 제대로 이용되지 않고 있다. 본 연구의 목적은 마이크로어레이 실험에 필요한 표본 수를 산정하는 데 있어 실제 마이크로어레이 자료의 재현성에 대한 정보를 이용하여 그 지침을 제공하는데 있다. 재현성 비교에서는 5가지 검정방법 즉, Fold change, Two-sample t-test, Wilcoxon rank-sum test, SAM, LPE 방법 별로 재현성을 측정하였다. 발현 값의 표준화 방법에 있어서는 MAS5, RMA 두 가지로 세분화 하였으며 반복수에 따라 상위 20개 또는 100개 유전자에 대한 일치성도 측정하였다. 또한, 표본수를 산정하는데 있어 기존에 제시한 방법에 현실적인 정보를 이용하여 좀 더 세분화하여 실험에 필요한 표본수를 산정해 보았다.