• 응용통계연구
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• 제26권2호
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• pp.307-319
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• 2013

마이크로어레이 실험의 특성상 표본의 수가 많지 않는 단점을 보완하고 분석 결과를 일반화하기 위하여 공개 저장소에 축적된 자료 중에 연구 목적이 동일한 여러 연구들을 통합하여 분석하려는 시도가 활발하다. 그러나 실험에서 사용한 플랫폼이 서로 다른 경우에는 유전자 관찰값의 분포가 달라지기 때문에 통합이 어렵고 최상의 통합 방법이 제시되어 있지 않다. 본 논문에서는 순위 기반 중위수, 분위수 이산화와 표준화를 각각 이용하여 변환한 자료값을 직접 합치거나 메타분석을 하여 연구 결과를 합치는 방법을 알아 보았다. 또한 GEO에서 다운받은 실제 자료들을 이용하여 네 가지 방법의 장단점과 효과를 비교하였고 서로 다른 연구 자료를 통합하는 것의 영향을 알아보았다.

• Restorative Dentistry and Endodontics
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• 제37권3호
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• pp.142-148
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• 2012

Objectives: We analyzed gene-expression profiles after 14 day odontogenic induction of human dental pulp cells (DPCs) using a DNA microarray and sought candidate genes possibly associated with mineralization. Materials and Methods: Induced human dental pulp cells were obtained by culturing DPCs in odontogenic induction medium (OM) for 14 day. Cells exposed to normal culture medium were used as controls. Total RNA was extracted from cells and analyzed by microarray analysis and the key results were confirmed selectively by reverse-transcriptase polymerase chain reaction (RT-PCR). We also performed a gene set enrichment analysis (GSEA) of the microarray data. Results: Six hundred and five genes among the 47,320 probes on the BeadChip differed by a factor of more than two-fold in the induced cells. Of these, 217 genes were upregulated, and 388 were down-regulated. GSEA revealed that in the induced cells, genes implicated in Apoptosis and Signaling by wingless MMTV integration (Wnt) were significantly upregulated. Conclusions: Genes implicated in Apoptosis and Signaling by Wnt are highly connected to the differentiation of dental pulp cells into odontoblast.

• Nutritional Sciences
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• 제8권1호
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• pp.23-27
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• 2005

The major garlic component, Allicin [diallylthiosulfinate, or (R, S)-diallyldissulfid-S-oxide] is known for its medicinal effects, such as antihypertensive activity, microbicidal activity, and antitumor activity. Allicin and diallyldisulfide, which is a converted form of allicin, inhibited the cholesterol level in hepatocytes, in vivo and in vitro. The metabolism of allicin reportedly occurs in the microsomes of hepatocytes, predominantly with the contribution of cytochrome P-450. However, little is known about how allicin affects the genes involved in the activity of hepatocytes in vivo. In the present study, we used the short-term intravenous injection of allicin to examine the in vivo genetic profile of hepatocytes. Allicin up-regulate ten genes in the hepatocytes. For example, the interferon regulator 1 (IRF-I), the wingless-related MMTV (mouse mammary tumor virus) integration site 4 (wnt-4), and the fatty acid binding protein 1. However, allicin down-regulated three genes: namely, glutathione S-transferase mu6, a-2-HS glycoprotein, and the corticosteroid binding globulin of hepatocytes. The up-regulated wnt-4, IRF-1, and mannose binding lectin genes can enhance the growth factors, cytokines, transcription activators and repressors that are involved in the immune defense mechanism. These primary data, which were generated with the aid of the Atlas Plastic Mouse 5 K Microarray, help to explain the mechanism which enables allicin to act as a therapeutic agent, to enhance immunity, and to prevent cancer. The data suggest that these benefits of allicin are partly caused by the up-regulated or down-regulated gene profiles of hepatocytes. To evaluate the genetic profile in more detail, we need to use a more extensive mouse genome array.

• Genomics & Informatics
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• 제7권2호
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• pp.122-130
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• 2009

A systems biology approach for the identification of perturbed molecular functions is required to understand the complex progressive disease such as breast cancer. In this study, we analyze the microarray data with Gene Ontology terms of molecular functions to select perturbed molecular functional modules in breast cancer tissues based on the definition of Gene ontology Functional Code. The Gene Ontology is three structured vocabularies describing genes and its products in terms of their associated biological processes, cellular components and molecular functions. The Gene Ontology is hierarchically classified as a directed acyclic graph. However, it is difficult to visualize Gene Ontology as a directed tree since a Gene Ontology term may have more than one parent by providing multiple paths from the root. Therefore, we applied the definition of Gene Ontology codes by defining one or more GO code(s) to each GO term to visualize the hierarchical classification of GO terms as a network. The selected molecular functions could be considered as perturbed molecular functional modules that putatively contributes to the progression of disease. We evaluated the method by analyzing microarray dataset of breast cancer tissues; i.e., normal and invasive breast cancer tissues. Based on the integration approach, we selected several interesting perturbed molecular functions that are implicated in the progression of breast cancers. Moreover, these selected molecular functions include several known breast cancer-related genes. It is concluded from this study that the present strategy is capable of selecting perturbed molecular functions that putatively play roles in the progression of diseases and provides an improved interpretability of GO terms based on the definition of Gene Ontology codes.

• 정보처리학회논문지D
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• 제15D권6호
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• pp.767-776
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• 2008

마이크로어레이 기술은 최근 실험적 분자생물학 분야에서 활발히 사용되고 있는 기술이다. 마이크로어레이 데이터는 한 번의 실험으로 수 만개의 유전자에 대한 발현값을 얻을 수 있으므로, 여러 질병의 발현형질을 연구하는데 매우 유용하게 사용된다. 마이크로어레이 데이터의 문제점은 참여하는 유전자의 수에 비해 참여하는 샘플(생물조직샘플)의 수가 매우 적고, 분류분석 기법을 사용하여 얻어진 분류자의 해석이 어렵다는 점이다. 본 연구에서는 위의 문제점을 해결하고자, 샘플 내 순위를 이용하여 동일한 생물학적 목적으로 수행된 공개 마이크로어레이 데이터를 통합하고, 순위 비교를 기반으로 하는 다양한 유전자 개수로 이루어진 암 분류 결정 규칙들로 이루어진 분류자를 제안한다. 본 분류자는 k개의 규칙으로 이루어진 앙상블 방법을 기반으로 하며, 하나의 규칙은 최대N개의 유전자, 관련유전자간의 순위비교 관계식, 판별클래스로 이루어져 있다. 하나의 규칙에 참여하는 유전자의 수를 다양하게 함으로써 좀더 신뢰성 높은 분류자를 생성할 수 있다. 또한 본 분류자는 생물학적 해석이용이하며, 분류자를 구성하는 유전자를 명확히 식별할 수 있고, 총 개수가 많지 않으므로 임상환경에서의 사용가능성도 생각해 볼 수 있다.

• BMB Reports
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• 제41권8호
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• pp.609-614
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• 2008

The concentrations and catalytic activities of enzymes control metabolic rates. Previous studies have focused on enzyme concentrations because there are no genome-wide techniques used for the measurement of enzyme activity. We propose a method for evaluating the significance of enzyme activity by integrating metabolic network topologies and genome-wide microarray gene expression profiles. We quantified the enzymatic activity of reactions and report the 388 significant reactions in five perturbation datasets. For the 388 enzymatic reactions, we identified 70 that were significantly regulated (P-value < 0.001). Thirty-one of these reactions were part of anaerobic metabolism, 23 were part of low-pH aerobic metabolism, 8 were part of high-pH anaerobic metabolism, 3 were part of low-pH aerobic reactions, and 5 were part of high-pH anaerobic metabolism.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.1003-1008
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• 2016

Breast cancer is now the leading cause of cancer death in women worldwide. Cancer progression is driven not only by cancer cell intrinsic alterations and interactions with tumor microenvironment, but also by systemic effects. Integration of multiple profiling data may provide insights into the underlying molecular mechanisms of complex systemic processes. We performed a bioinformatic analysis of two public available microarray datasets for breast tumor stroma and peripheral blood mononuclear cells, featuring integrated transcriptomics data, protein-protein interactions (PPIs) and protein subcellular localization, to identify genes and biological pathways that contribute to dialogue between tumor stroma and the peripheral circulation. Genes of the integrin family as well as CXCR4 proved to be hub nodes of the crosstalk network and may play an important role in response to stroma-derived chemoattractants. This study pointed to potential for development of therapeutic strategies that target systemic signals travelling through the circulation and interdict tumor cell recruitment.