• 생물정신의학
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• 제1권1호
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• pp.60-66
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• 1994

Advances in molecular biology have renewed hope for the discovery of disease relevant gene. The basic strategy is gene mapping and likely to have on important role in psychiatric research and practice. Recent linkage studies of chromosomal loci to psychiatric diseases shed light on the potential for new genetics in psychiatric science. This article reviews molecular application to psychiatrymethodological issues in genetic linkage, study of gene expression by analysis of mRNA, and current linkage studies in psychiatric diseases.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2000년도 International Symposium on Bioinformatics
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• pp.39-40
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• 2000

Knowledge discovery has attracted increased attention in the biomedical industry in recent years is due to the increased availability of huge amount of biomedical data and the imminent need to turn such data into useful information and knowledge. In this talk, we discuss knowledge discovery techniques for gene expression analysis and MHC-peptide binding prediction in the context of discovering protein antigens and hot spots in these antigens.

• Journal of Genetic Medicine
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• 제10권1호
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• pp.13-19
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• 2013

Retinitis pigmentosa (RP) is the most common hereditary retinal disorder and is characterized by progressive retinal degeneration and decline in vision. RP comprises a heterogeneous group of disorders caused by various genetic variants. Since the first discovery of the causal mutation in the RHO gene using positional cloning, numerous mutations have been detected in more than 60 loci and 50 genes. However, causal genes have not been discovered in about 50% of cases. We attempt here to review the strategies to identify causal alleles of retinitis pigmentosa. These include conventional methods as well as state-of-the-art technologies based on next-generation sequencing.

• Communications for Statistical Applications and Methods
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• 제25권5호
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• pp.559-568
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• 2018

Gene classification can involve complex order-restricted inference. Examining gene expression pattern across groups with order-restriction makes standard statistical inference ineffective and thus, requires different methods. For this problem, Roy's union-intersection principle has some merit. The M-estimator adjusting for outlier arrays in a microarray study produces a robust test statistic with distribution-insensitive clustering of genes. The M-estimator in conjunction with a union-intersection principle provides a nonstandard robust procedure. By exact permutation distribution theory, a conditionally distribution-free test based on the proposed test statistic generates corresponding p-values in a small sample size setup. We apply a false discovery rate (FDR) as a multiple testing procedure to p-values in simulated data and real microarray data. FDR procedure for proposed test statistics controls the FDR at all levels of ${\alpha}$ and ${\pi}_0$ (the proportion of true null); however, the FDR procedure for test statistics based upon normal theory (ANOVA) fails to control FDR.

• Biomolecules & Therapeutics
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• 제25권1호
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• pp.80-90
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• 2017

Initial discovery on sphingosine 1-phosphate (S1P) as an intracellular second messenger was faced unexpectedly with roles of S1P as a first messenger, which subsequently resulted in cloning of its G protein-coupled receptors, $S1P_{1-5}$. The molecular identification of S1P receptors opened up a new avenue for pathophysiological research on this lipid mediator. Cellular and molecular in vitro studies and in vivo studies on gene deficient mice have elucidated cellular signaling pathways and the pathophysiological meanings of S1P receptors. Another unexpected finding that fingolimod (FTY720) modulates S1P receptors accelerated drug discovery in this field. Fingolimod was approved as a first-in-class, orally active drug for relapsing multiple sclerosis in 2010, and its applications in other disease conditions are currently under clinical trials. In addition, more selective S1P receptor modulators with better pharmacokinetic profiles and fewer side effects are under development. Some of them are being clinically tested in the contexts of multiple sclerosis and other autoimmune and inflammatory disorders, such as, psoriasis, Crohn's disease, ulcerative colitis, polymyositis, dermatomyositis, liver failure, renal failure, acute stroke, and transplant rejection. In this review, the authors discuss the state of the art regarding the status of drug discovery efforts targeting S1P receptors and place emphasis on potential clinical applications.

• 한국인삼전략화협의회:학술대회논문집
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• 한국인삼전략화협의회 2003년도 제4차 한국인삼약초산업 전략화 세미나
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• pp.54-63
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• 2003

"Korea ginseng (Panax ginseng C.A Meyer) is an important medicinal plant. Its root has been used as an herbal medicine that provides resistance to stress and disease, and prevents exhaustion since the ancient time. Ginsenosides, glycosylated triterpene (saponin), are considered to be the main active compounds of the ginseng root. Despite of considerable commercial interests of ginsenosides, very little is known about the genes and their biochemical pathways for ginsenoside biosynthesis. This work will focus on the identification of genes involved in ginsenoside biosynthesis and the dissection of ginsenoside biosynthetic pathway using a functional genomics tool. Expression sequence tags (ESTs) provide a valuable tool to discovery the genes in secondary metabolite biosynthesis. We generated over 21,155 ginseng ESTs that is now sufficient to facilitate discovering the genes involved in ginsenoside biosynthesis such as oxidosqualene cyclase(OSC), cytochrome P450 and glycosyltransferase. With ESTs information, microarray technology will be used for the analysis of gene expression, and the identification of genes including transcription factors expressed in tissues under given experimental condition. Heterogous system such as yeast and plants will allow us to do the functional analysis. And selected ginseng hairy root which show variation in ginsenoside production will be used as a material for functional analysis of candidate gene. Functional genomics approach will successfully accelerate gene discovery, and also provide promises of metabolic engineering for the ginsenoside production."

• Genomics & Informatics
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• 제13권3호
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• pp.76-80
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• 2015

Type 2 diabetes mellitus is a complex metabolic disorder associated with multiple genetic, developmental and environmental factors. The recent advances in gene expression microarray technologies as well as network-based analysis methodologies provide groundbreaking opportunities to study type 2 diabetes mellitus. In the present study, we used previously published gene expression microarray datasets of human skeletal muscle samples collected from 20 insulin sensitive individuals before and after insulin treatment in order to construct insulin-mediated regulatory network. Based on a motif discovery method implemented by iRegulon, a Cytoscape app, we identified 25 candidate regulons, motifs of which were enriched among the promoters of 478 up-regulated genes and 82 down-regulated genes. We then looked for a hierarchical network of the candidate regulators, in such a way that the conditional combination of their expression changes may explain those of their target genes. Using Genomica, a software tool for regulatory network construction, we obtained a hierarchical network of eight regulons that were used to map insulin downstream signaling network. Taken together, the results illustrate the benefits of combining completely different methods such as motif-based regulatory factor discovery and expression level-based construction of regulatory network of their target genes in understanding insulin induced biological processes and signaling pathways.

• Journal of Genetic Medicine
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• 제20권2호
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• pp.31-38
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• 2023

Rare diseases, even though defined as fewer than 20,000 in South Korea, with over 8,000 rare Mendelian disorders having been identified, they collectively impact 6-8% of the global population. Many of the rare diseases pose significant challenges to patients, patients' families, and the healthcare system. The diagnostic journey for rare disease patients is often lengthy and arduous, hampered by the genetic diversity and phenotypic complexity of these conditions. With the advent of next-generation sequencing technology and clinical implementation of exome sequencing (ES) and genome sequencing (GS), the diagnostic rate for rare diseases is 25-50% depending on the disease category. It is also allowing more rapid new gene-disease association discovery and equipping us to practice precision medicine by offering tailored medical management plans, early intervention, family planning options. However, a substantial number of patients remain undiagnosed, and it could be due to several factors. Some may not have genetic disorders. Some may have disease-causing variants that are not detectable or interpretable by ES and GS. It's also possible that some patient might have a disease-causing variant in a gene that hasn't yet been linked to a disease. For patients who remain undiagnosed, reanalysis of existing data has shown promises in providing new molecular diagnoses achieved by new gene-disease associations, new variant discovery, and variant reclassification, leading to a 5-10% increase in the diagnostic rate. More advanced approach such as long-read sequencing, transcriptome sequencing and integration of multi-omics data may provide potential values in uncovering elusive genetic causes.

• Journal of the Korean Data and Information Science Society
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• 제25권5호
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• pp.971-986
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• 2014

동시에 여러 개의 가설검정 수행시 귀무가설이 참일 경우 귀무가설을 기각할 확률이 커지는 문제가 발생한다. 이러한 다중검정 문제 해결을 위해 여러 연구에서는 가설검정시 필요한 집단별 오류율(FWER; family-wise error rate), 위발견율 (FDR; false discovery rate) 또는 위비발견율 (FNR; false nondiscovery rate) 과 통계량을 고려하여 검정력을 높이고자 하였다. 본 연구에서는 T 통계량, 수정된 T 통계량, 그리고 LPE (local pooled error) 통계량 기반 P값을 이용한 Bonferroni (1960) 방법, Holm (1979) 방법, Benjamini와 Hochberg (1995) 방법과 Benjamini와 Yekutieli (2001) 방법 그리고 Z 통계량 기반 Sun과 Cai (2007) 방법을 고찰하고 모의실험을 통해 다중검정 능력을 비교하였다. 또한 실제 데이터로 애기장대 유전자 발현 데이터에 대해 여러 가지 다중검정법을 통해 유의한 유전자들을 선별하였다.

• IMMUNE NETWORK
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• 제24권1호
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• pp.1.1-1.6
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• 2024

IL-18 binding protein (IL-18BP) was originally discovered in 1999 while attempting to identify an IL-18 receptor ligand binding chain (also known as IL-18Rα) by subjecting concentrated human urine to an IL-18 ligand affinity column. The IL-18 ligand chromatography purified molecule was analyzed by protein microsequencing. The result revealed a novel 40 amino acid polypeptide. To isolate the complete open reading frame (ORF), various human and mouse cDNA libraries were screened using cDNA probe derived from the novel IL-18 affinity column bound molecule. The identified entire ORF gene was thought to be an IL-18Rα gene. However, IL-18BP has been proven to be a unique soluble antagonist that shares homology with a variety of viral proteins that are distinct from the IL-18Rα and IL-18Rβ chains. The IL-18BP cDNA was used to generate recombinant IL-18BP (rIL-18BP), which was indispensable for characterizing the role of IL-18BP in vitro and in vivo. Mammalian cell lines were used to produce rIL-18BP due to its glycosylation-dependent activity of IL-18BP (approximately 20 kDa). Various forms of rIL-18BP, intact, C-terminal his-tag, and Fc fusion proteins were produced for in vitro and in vivo experiments. Data showed potent neutralization of IL-18 activity, which seems promising for clinical application in immune diseases involving IL-18. However, it was a long journey from discovery to clinical use although there have been various clinical trials since IL-18BP was discovered in 1999. This review primarily covers the discovery of IL-18BP along with how basic research influences the clinical development of IL-18BP.