• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.2793-2800
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• 2015

In molecular-targeted cancer therapy, acquired resistance to gemcitabine is a major clinical problem that reduces its effectiveness, resulting in recurrence and metastasis of cancers. In spite of great efforts to reveal the overall mechanism of acquired gemcitabine resistance, no definitive genetic factors have been identified that are absolutely responsible for the resistance process. Therefore, we performed a cross-platform meta-analysis of three publically available microarray datasets for cancer cell lines with acquired gemcitabine resistance, using the R-based RankProd algorithm, and were able to identify a total of 158 differentially expressed genes (DEGs; 76 up- and 82 down-regulated) that are potentially involved in acquired resistance to gemcitabine. Indeed, the top 20 up- and down-regulated DEGs are largely associated with a common process of carcinogenesis in many cells. For the top 50 up- and down-regulated DEGs, we conducted integrated analyses of a gene regulatory network, a gene co-expression network, and a protein-protein interaction network. The identified DEGs were functionally enriched via Gene Ontology hierarchy and Kyoto Encyclopedia of Genes and Genomes pathway analyses. By systemic combinational analysis of the three molecular networks, we could condense the total number of DEGs to final seven genes. Notably, GJA1, LEF1, and CCND2 were contained within the lists of the top 20 up- or down-regulated DEGs. Our study represents a comprehensive overview of the gene expression patterns associated with acquired gemcitabine resistance and theoretical support for further clinical therapeutic studies.

• 한국정보처리학회:학술대회논문집
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• 한국정보처리학회 2008년도 추계학술발표대회
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• pp.340-343
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• 2008

유전자들은 복잡한 상호작용을 통해 세포의 기능이 조절된다. 상호작용하는 유전자 그룹들을 유전자 조절 네트워크라고 한다. 기존의 유전자 조절 네트워크는 2D microarray 데이터를 이용하여 시간의 흐름에 따른 유전자간의 상호작용을 알 수가 없었다. 이 논문에서는 시간의 변화에 따른 유전자들 간의 조절관계를 살펴 볼 수 있는 조절네트워크 모델링의 방법을 제시한다. 유전자의 발현양을 표시하기 위해 이진 이산화 방법을 사용하였고 3D microarray 데이터에서 유전자 발현 패턴을 찾기 위해 Cube mining 알고리즘을 적용하였고, 유전자간의 관계를 밝히기 위해 시간 관계 규칙탐사 기법을 사용하여 유전자들 간의 시간 관계를 포함한 유전자 조절네트워크를 구축하였다. 이 연구는 시간의 흐름에 따른 유전자간의 상호작용을 알 수 있으며, 모델링된 조절 네트워크를 이용하여 기능이 아직 발견되지 않은 유전자들의 기능을 예측 할 수 있다.

• 한국정보과학회:학술대회논문집
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• 한국정보과학회 2005년도 가을 학술발표논문집 Vol.32 No.2 (2)
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• pp.277-279
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• 2005

DNA 마이크로어레이 기술의 발전으로 유전자 발현에 대한 많은 양의 정보가 쏟아지게 되었고, 이러한 정보들을 이용하여 유전자 조절 네트워크를 수학적으로 모델링하는 것이 시스템 생물학의 중요 관심사로 떠오르고 있다. 본 논문에서는 실험에서 얻어낸 데이터를 유전 프로그래밍을 이용한 기호 회귀를 통해 데이터 지점을 조정하고 유전 프로그래밍의 결과 함수를 이용해 각 지점에서의 미분값을 얻어내었다. 그 뒤, 불리안 네트워크를 표현하는 이진 배열과 S-시스템을 표현하는 실수 배열을 결합한 해를 사용하는 유전 알고리즘으로 앞에서 얻은 데이터를 이용해 원하는 S-시스템의 구조와 매개변수를 구해내었다.

• Fisheries and Aquatic Sciences
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• 제26권6호
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• pp.406-422
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• 2023

Sarcopenia is an age-related, progressive skeletal muscle disorder involving the loss of muscle mass and strength. Previous studies have shown that γ-aminobutyric acid (GABA) from fermented oysters aids in regulatory T cells (Tregs) cell expansion and function by enhancing autophagy, and concomitantly mediate muscle regeneration by modulating muscle inflammation and satellite cell function. The fermentation process of oysters not only increases the GABA content but also enhances the content of branched amino acids and free amino acids that aid the level of protein absorption and muscle strength, mass, and repair. In this study, the effect of GABA-enriched fermented sarco oyster extract (FSO) on reduced muscle mass and functions via Treg modulation and enhanced autophagy in aged mice was investigated. Results showed that FSO enhanced the expression of autophagy markers (autophagy-related gene 5 [ATG5] and GABA receptor-associated protein [GABARAP]), forkhead box protein 3 (FoxP3) expression, and levels of anti-inflammatory cytokines (interleukin [IL]-10 and transforming growth factor [TGF]-β) secreted by Tregs while reducing pro-inflammatory cytokine levels (IL-17A and interferon [IFN]-γ). Furthermore, FSO increased the expression of IL-33 and its receptor IL-1 receptor-like 1 (ST2); well-known signaling pathways that increase amphiregulin (Areg) secretion and expression of myogenesis markers (myogenic factor 5, myoblast determination protein 1, and myogenin). Muscle mass and function were also enhanced via FSO. Overall, the current study suggests that FSO increased autophagy, which enhanced Treg accumulation and function, decreased muscle inflammation, and increased satellite cell function for muscle regeneration and therefore could decrease the loss of muscle mass and function with aging.

• 한국컴퓨터정보학회논문지
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• 제15권12호
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• pp.197-207
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• 2010

대용량(High-throughput) 형태로 얻어진 cDNA 마이크로어레이 데이터에 다양한 데이터 마이닝 기법을 적용하면 서로 다른 조직에서 추출한 유전자의 발현정도를 비교할 수 있고 정상세포와 암세포에서 발현량의 차이를 보이는 DEG(Differently Expression Gene) 유전자를 추출할 수 있다. 이들을 이용하여 병을 진단할 수 있을 뿐만 아니라, 암의 진행 단계(Cancer Stage)에 따른 치료 방법을 결정할 수 있다. 마이크로어레이를 기반으로 한 대부분의 암 분류자는 기계학습 기법을 이용하여 암 관련 유전자를 추출하여, 이들 유전자를 총체적으로 이용하여 독립 샘플의 클래스(암, 정상)를 판정한다. 하지만 유전자의 발현량의 차이뿐만 아니라 유전자와 유전자의 상관관계의 변화가 질병 진단에 활용될 수 있다. 대부분의 질병은 단독 유전자의 변이에 의한 것이 아니라 유전자의 모듈로 이루어진 유전자조절네트워크의 변이에 의한 것이기 때문이다. 본 논문에서는 조건에 따라 특이적 관계를 나타내는 유전자 쌍을 식별하여, 이들 유전자 쌍을 이용한 유전자 분류 모듈을 생성한다. 분류 모듈을 이용한 암 분류 방법이 기존의 암 분류 방법보다 높은 정확도로 암과정상 샘플을 분류함을 보여주고 있다. 분류 모듈을 구성하는 유전자의 수가 상대적으로 적으므로 임상키트로의 개발도 고려할 수 있다. 향후 분류 모듈에 속하는 유전자의 기능적 검증을, GO(Gene Ontology)를 활용함으로서, 밝혀지지 않은 새로운 암 관련 유전자를 식별하고, 분류 모듈을 확대하여 암 특이적 유전자조절네트워크 구성에 활용할 계획이다.

• Asian-Australasian Journal of Animal Sciences
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• 제30권8호
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• pp.1183-1189
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• 2017

Objective: Owing to the public availability of complete genome sequences, including avian species, massive bioinformatics analyses may be conducted for computational gene prediction and the identification of gene regulatory networks through various informatics tools. However, to evaluate the biofunctional activity of a predicted target gene, in vivo and in vitro functional genomic analyses should be a prerequisite. Methods: Due to a lack of quail genomic sequence information, we first identified the partial genomic structure and sequences of the quail SH3 domain containing ring finger 2 (SH3RF2) gene. Subsequently, SH3RF2 was knocked out using clustered regularly interspaced short palindromic repeat/Cas9 technology and single cell-derived SH3RF2 mutant sublines were established to study the biofunctional activity of SH3RF2 in quail myoblast (QM7) cells during muscle differentiation. Results: Through a T7 endonuclease I assay and genotyping analysis, we established an SH3RF2 knockout (KO) QM7#4 subline with 61 and 155 nucleotide deletion mutations in SH3RF2. After the induction of myotube differentiation, the expression profiles were analyzed and compared between regular QM7 and SH3RF2 KO QM7#4 cells by global RNA sequencing and bioinformatics analysis. Conclusion: We did not detect any statistically significant role of SH3RF2 during myotube differentiation in QM7 myoblast cells. However, additional experiments are necessary to examine the biofunctional activity of SH3RF2 in cell proliferation and muscle growth.

• Genes and Genomics
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• 제40권12호
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• pp.1363-1371
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• 2018

One of the main concerns in biology is extracting sophisticated features from DNA sequence for gene interaction determination, receiving a great deal of researchers' attention. The epigenetic modifications along with their patterns have been intensely recognized as dominant features affecting on gene expression. However, studying sequenced-based features highly correlated to this key element has remained limited. The main objective in this research was to propose a new feature highly correlated to epigenetic modifications capable of classification of genes. In this paper, classification of 34 genes in PPAR signaling pathway associated with muscle fat tissue in human was performed. Using different statistical outlier detection methods, we proposed that 5-mers highly correlated to epigenetic modifications can correctly categorize the genes involved in the same biological pathway or process. Thirty-four genes in PPAR signaling pathway were classified via applying a proposed feature, 5-mers strongly associated to 17 different epigenetic modifications. For this, diverse statistical outlier detection methods were applied to specify the group of thoroughly correlated genes. The results indicated that these 5-mers can appropriately identify correlated genes. In addition, our results corresponded to GeneMania interaction information, leading to support the suggested method. The appealing findings imply that not only epigenetic modifications but also their highly correlated 5-mers can be applied for reconstructing gene regulatory networks as supplementary data as well as other applications like physical interaction, genes prioritization, indicating some sort of data fusion in this analysis.

• 생명과학회지
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• 제28권10호
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• pp.1233-1243
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• 2018

SREBPs는 지질의 항상성 및 대사를 조절하는 전사 인자이다. 이들은 내인성 콜레스테롤, 지방산(FA), 트리아실글리세롤(TG) 및 인지질 합성에 필요한 효소의 발현을 정밀하게 조절한다. 3종류의 SREBP 단백질은 2개의 다른 유전자에 의해 암호화 된다. SREBP1 유전자는 SREBP-1a와 SREBP-1c를 만든다. 이는 RNA의 alternative splicing에 의한 대체 프로모터의 이용으로부터 유도된다. SREBP-2는 별도의 유전자에서 유래한다. 또한, SREBPs는 ER 스트레스, 염증, 자가포식 및 세포사멸과 같은 수많은 병인과정에 관여하며, 비만, 이상 지질혈증, 당뇨병 및 비알콜성 지방간 질환 등을 유발하는 것으로 알려져 있다. 유전체의 분석은 SREBPs가 생물학적 신호 전달, 세포 신진 대사, 및 성장을 조절하는 중요한 연결고리임을 보여 주었다. 이 과정에서 SREBP는 PI3K-Akt-mTOR 경로를 통해 활성화 된다고 알려져 있다. 하지만 정확한 분자 메커니즘은 좀더 밝혀져야 한다. 이 리뷰에서는 세포, 기관 및 생물개체 수준의 생리학 및 병태 생리학 영역에서 SREBP의 역할에 대한 포괄적인 이해를 넓혀 줄 것이다.

• 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.

• Journal of Microbiology and Biotechnology
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• 제21권4호
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• pp.438-447
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• 2011

Deinococcus radiodurans is extremely resistant to various genotoxic conditions and chemicals. In this study, we characterized the effect of a sublethal concentration (100 ${\mu}M$) of cadmium (Cd) on D. radiodurans using a whole-genome DNA microarray. Time-course global gene expression profiling showed that 1,505 genes out of 3,116 total ORFs were differentially expressed more than 2-fold in response to Cd treatment for at least one timepoint. The majority of the upregulated genes are related to iron uptake, cysteine biosynthesis, protein disulfide stress, and various types of DNA repair systems. The enhanced upregulation of genes involved in cysteine biosynthesis and disulfide stress indicate that Cd has a high affinity for sulfur compounds. Provocation of iron deficiency and growth resumption of Cd-treated cells by iron supplementation also indicates that CdS forms in iron-sulfur-containing proteins such as the [Fe-S] cluster. Induction of base excision, mismatch, and recombinational repair systems indicates that various types of DNA damage, especially base excision, were enhanced by Cd. Exposure to sublethal Cd stress reduces the growth rate, and many of the downregulated genes are related to cell growth, including biosynthesis of cell membrane, translation, and transcription. The differential expression of 52 regulatory genes suggests a dynamic operation of complex regulatory networks by Cd-induced stress. These results demonstrate the effect of Cd exposure on D. radiodurans and how the related genes are expressed by this stress.