• Journal of the Korean Data and Information Science Society
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• 제27권1호
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• pp.225-243
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• 2016

Thanks to recent advance of next generation sequencing techniques, RNA-seq enabled to have an unprecedented opportunity to identify transcript variants with isoform diversity and allelic imbalance (Anders et al., 2012) by different transcriptional rates. To date, it is well known that those features might be associated with the aberrant patterns of disease complexity such as tissue (Anders and Huber, 2010; Anders et al., 2012; Nariai et al., 2014) specific differential expression at isoform levels or tissue specific allelic imbalance in mal-functionality of disease processes, etc. Nevertheless, the knowledge of post-transcriptional modification and AI in transcriptomic and genomic areas has been little known in the traditional platforms due to the limitation of technology and insufficient resolution. We here stress the potential of isoform variability and allelic specific expression that are relevant to the abnormality of disease mechanisms in transcriptional genetic regulatory networks. In addition, we systematically review how robust Bayesian approaches in RNA-seq have been developed and utilized in this regard in the field.

• 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.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2005년도 BIOINFO 2005
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• pp.197-201
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• 2005

When we want to find out the regulatory relationships between genes from gene expression data, dimensionality is one of the big problem. In general, the size of search space in modeling the regulatory relationships grows in O(n$^2$) while the number of genes is increasing. However, hopefully it can be reduced to O(kn) with selected k by applying divide and conquer heuristics which depend on some assumptions about genetic network. In this paper, we approach the modeling problem in divide-and-conquer manner. We applied clustering to make the problem into small sub-problems, then hierarchical model process is applied to those small sub-problems.

• Journal of Microbiology and Biotechnology
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• 제16권11호
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• pp.1661-1677
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• 2006

Rhizobium and related genera are soil bacteria with great metabolic plasticity. These microorganisms survive in many different environments and are capable of eliciting the formation of nitrogen-fixing nodules on legumes. The successful establishment of symbiosis is precisely regulated and requires a series of signal exchanges between the two partners. Quorum sensing (QS) is a prevalent form of population density-dependent gene regulation. Recently, increasing evidence indicates that rhizobial quorum sensing provides a pervasive regulatory network, which plays a more generalized role in the physiological activity of free-living rhizobia, as well as during symbiosis. Several rhizobia utilize multiple, overlapping quorum sensing systems to regulate diverse properties, including conjugal transfer and copy number control of plasmids, exopolysaccharide biosynthesis, rhizosphere-related functions, and cell growth. Genomic and proteomic analyses have begun to reveal the wide range of functions under quorum-sensing control.

• Bioinformatics and Biosystems
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• 제2권2호
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• pp.52-57
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• 2007

The computational discovery of transcription factor binding site is one of the important tools in the genetic and genomic analysis. Rough prediction of gene regulation network and finding possible co-regulated genes are typical applications of the technique. Countless motif-discovery algorithms have been proposed for the past years. However, there is no dominant algorithm yet. Each algorithm does not give enough accuracy without extensive information. In this paper, we explore the possibility of combining multiple algorithms for the one integrated result in order to improve the performance and the convenience of researchers. Moreover, we apply new high order information that is reorganized from the set of basis predictions to the final prediction.

• 생명과학회지
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• 제26권8호
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• pp.904-910
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• 2016

가축의 경제형질은 대부분 복합형질 상태이며, 많은 유전자와 생물대사회로에 의해 조절된다. 시스템 생물학은 생명현상을 하나의 복합체로 가정하고, 형질에 관여하는 유전자들에 대한 기능적 관계를 분석하는 학문이다. 유전자 네트워크는 시스템 생물학의 하나의 연구분야로써, 유전자 기능의 상관관계를 지도화하여 오믹스 데이터를 통합 분석하여 해석한다. 유전자 네트워크는 단백질-단백질 상호작용, 공발현, 조절인자, 유전자형 기반으로 다양한 유전자의 기능적 상호작용을 표현할 수 있다. 또한, 네트워크를 구성하기 위해서는 유전자 간 연결 정도에 가중치를 두거나, 인접한 유전자 수 계산 등의 네트워크 토폴로지 알고리즘이 적용된다. 가축에서는 이러한 연구가 단형질에 대한 유전자 발현, 단백질 상호작용 등에 국한되어 있는 실정이다. 본 논문에서는 유전자 공발현 네트워크와 단백질-단백질 상호작용 네트워크 분석법을 확립하고 소의 102개 경제형질에 대하여 유전자 네트워크 분석 결과에 대한 데이터베이스를 구축하였다. 102개의 경제형질은 Animal Trait Ontology (ATO) 명명법에 의하여 분류하여 제공하였다. 각 형질에 포함된 유전자 리스트는 Animal QTL database에서 제공하는 양적유전형질좌위의 물리적 위치에 존재하는 유전자군을 추출하였다. 유전자 공발현 네트워크는 R의 WGCNA 패키지를 활용하였으며, 단백질-단백질 상호작용 네트워크는 Human Protein Reference Database에서 사람과 소의 orthologous group에 포함된 유전자를 대상으로 단백질 상호작용 관계를 규명하였다. 네트워크 분석 결과는 관계형 테이블로 구축하였으며, 구축한 데이터베이스를 관련 연구진에게 공유하기 위하여 웹 기반의 유전자 네트워크 가시화 시스템을 구현하였다(http://www.nabc.go.kr/cg). 웹 데이터베이스 구현을 위하여 Ontle 프로그램을 활용하여 다양한 방식으로 유전자 네트워크 가시화 작업을 수행하였다. 이 시스템을 통하여 사용자는 관련 형질의 후보 유전자군 탐색, 유전자 네트워크 분석 결과, 유전자 사이의 기능적 연결관계를 손쉽게 살펴볼 수 있게 될 것이다.

• Genomics & Informatics
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• 제12권4호
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• pp.181-186
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• 2014

Genome-wide association studies have proven the highly polygenic architecture of complex diseases or traits; therefore, single-locus-based methods are usually unable to detect all involved loci, especially when individual loci exert small effects. Moreover, the majority of associated single-nucleotide polymorphisms resides in non-coding regions, making it difficult to understand their phenotypic contribution. In this work, we studied epistatic interactions associated with three common diseases using Korea Association Resource (KARE) data: type 2 diabetes mellitus (DM), hypertension (HT), and coronary artery disease (CAD). We showed that epistatic single-nucleotide polymorphisms (SNPs) were enriched in enhancers, as well as in DNase I footprints (the Encyclopedia of DNA Elements [ENCODE] Project Consortium 2012), which suggested that the disruption of the regulatory regions where transcription factors bind may be involved in the disease mechanism. Accordingly, to identify the genes affected by the SNPs, we employed whole-genome multiple-cell-type enhancer data which discovered using DNase I profiles and Cap Analysis Gene Expression (CAGE). Assigned genes were significantly enriched in known disease associated gene sets, which were explored based on the literature, suggesting that this approach is useful for detecting relevant affected genes. In our knowledge-based epistatic network, the three diseases share many associated genes and are also closely related with each other through many epistatic interactions. These findings elucidate the genetic basis of the close relationship between DM, HT, and CAD.

• IMMUNE NETWORK
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• 제16권3호
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• pp.176-182
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• 2016

CCR3 is a chemokine receptor that mediates the accumulation of allergic inflammatory cells, including eosinophils and Th2 cells, at inflamed sites. The regulatory sequence of the CCR3 gene, contains two Runt-related transcription factor (RUNX) 1 sites and two PU.1 sites, in addition to a functional GATA site for transactivation of the CCR3 gene. In the present study, we examined the effects of the cis-acting elements of RUNX1 and PU.1 on transcription of the gene in EoL-1 eosinophilic cells and Jurkat T cells, both of which expressed functional surface CCR3 and these two transcription factors. Introduction of RUNX1 siRNA or PU.1 siRNA resulted in a modest decrease in CCR3 reporter activity in both cell types, compared with transfection of GATA-1 siRNA. Cotransfection of the two siRNAs led to inhibition in an additive manner. EMSA analysis showed that RUNX1, in particular, bound to its binding motifs. Mutagenesis analysis revealed that all point mutants lacking RUNX1- and PU.1-binding sites exhibited reduced reporter activities. These results suggest that RUNX1 and PU.1 participate in transcriptional regulation of the CCR3 gene.

• Asian-Australasian Journal of Animal Sciences
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• 제25권10호
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• pp.1481-1492
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• 2012

The interaction of the genes involved in intestinal development is the molecular basis of the regulatory mechanisms of intestinal development. The objective of this study was to identify the significant pathways and key genes that regulate intestinal development in Landrace piglets, and elucidate their rules of operation. The differential expression of genes related to intestinal development during suckling time was investigated using a porcine genome array. Time sequence profiles were analyzed for the differentially expressed genes to obtain significant expression profiles. Subsequently, the most significant profiles were assayed using Gene Ontology categories, pathway analysis, network analysis, and analysis of gene co-expression to unveil the main biological processes, the significant pathways, and the effective genes, respectively. In addition, quantitative real-time PCR was carried out to verify the reliability of the results of the analysis of the array. The results showed that more than 8000 differential expression transcripts were identified using microarray technology. Among the 30 significant obtained model profiles, profiles 66 and 13 were the most significant. Analysis of profiles 66 and 13 indicated that they were mainly involved in immunity, metabolism, and cell division or proliferation. Among the most effective genes in these two profiles, CN161469, which is similar to methylcrotonoyl-Coenzyme A carboxylase 2 (beta), and U89949.1, which encodes a folate binding protein, had a crucial influence on the co-expression network.

• 생명과학회지
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• 제8권3호
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• pp.263-271
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• 1998

전사조절인자로서 잘 알려져 있는 cAMP receptor protein(CRP)은 cAMP와 DNA에 결합하는 특별한 활성을 가지고 있으며, cAMP-CRP complex를 형성하여 수많은 유전자의 발현조절에 관여한다. 이러한 측면에서 cAMP-CRP의 조절은 어떤 면에서 총체적 조절체계라고까지 한다.본 연구는 Serratia 균주에서 crp 유전자의 분자적 특성 및 cAMP에 의한 발현조절을 받는 분자기구를 해석하고자 유전자를 클로닝하고 발현을 확인하였다. MacConkey 배지에서 maltose를 탄소원으로 충분히 이용하지 못하는 대장균 TP2139(${\Delta}crp$,${\Delta}lac$를 숙주로 이용하고, 염색체 DNA를 library로 작성하여 얻은 형질전환체 약 일만개의 콜로니에서 red colony를 나타내는 5종류의 양성 클론을 얻었다. 이들 클론을 Southern 방법으로 확인한 결과 3kh의 단편을 가진 pCKB12클론이 crp유전자를 coding하고 있음을 확인하였다. glpD-lacZ 융합 plasmid인 pLDC6의 BamHI부위에 pCKB12의 3kb 단편을 삽입시킨 재조합 plasmid pLDC6-Scrp를 작성하여, 클로닝된 Serratia의 crp유전자가 대장균에서 유전자 전사조절에 미치는 영향을 확인한 결과 cAMP-CRP 복합체 형성에 의한 전사조절 기능이 확인되어졌다.