• Title/Summary/Keyword: -omics

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Perspectives of Integrative Cancer Genomics in Next Generation Sequencing Era

  • Kwon, So-Mee;Cho, Hyun-Woo;Choi, Ji-Hye;Jee, Byul-A;Jo, Yun-A;Woo, Hyun-Goo
    • Genomics & Informatics
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    • v.10 no.2
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    • pp.69-73
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    • 2012
  • The explosive development of genomics technologies including microarrays and next generation sequencing (NGS) has provided comprehensive maps of cancer genomes, including the expression of mRNAs and microRNAs, DNA copy numbers, sequence variations, and epigenetic changes. These genome-wide profiles of the genetic aberrations could reveal the candidates for diagnostic and/or prognostic biomarkers as well as mechanistic insights into tumor development and progression. Recent efforts to establish the huge cancer genome compendium and integrative omics analyses, so-called "integromics", have extended our understanding on the cancer genome, showing its daunting complexity and heterogeneity. However, the challenges of the structured integration, sharing, and interpretation of the big omics data still remain to be resolved. Here, we review several issues raised in cancer omics data analysis, including NGS, focusing particularly on the study design and analysis strategies. This might be helpful to understand the current trends and strategies of the rapidly evolving cancer genomics research.

Quantitative and Comparative Analysis of Urinary Steroid Levels upon Treatment of an Anti-Diabetic Drug, CKD-501 using Gas Chromatography-Mass Spectrometry

  • Sadanala, Krishna Chaitanya;Jung, Byung-Hwa;Jang, In-Jin;Chung, Bong-Chul
    • Journal of Pharmaceutical Investigation
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    • v.41 no.1
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    • pp.37-43
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    • 2011
  • Urinary steroid levels were investigated in the treatment of CKD-501, a new anti-diabetic drug candidate. CKD-501 was administered orally at the dosage of 1, 2, 4 mg/day for 7 days to normal men (n=18). Urine was collected before, during and after stopping the drug administration and the urinary level of androgen, estrogen, progestin and corticoids were quantified using GC-MS (gas chromatography-mass spectrometry). Only urinary corticosteroid and an androgen, DHEA levels among all the analyzed steroids, have been found to increase progressively, reaching significant levels on the last day of drug treatment and later declined after the drug treatment is withdrawn. Therefore, it was thought that an increase in the urinary corticoid and DHEA levels could be a characteristic of CKD-501, since it prominently acts on the glucose sensitivity and suppresses the triglyceride levels. In conclusion, it was found that CKD-501, an anti-diabetic drug candidate, affects the glucocorticoid and DHEA levels and it plays a crucial role in glucose homeostasis.

Impacts of glycans attached to therapeutic glycoproteins (의약용 당단백질에 부가된 당사슬의 중요성)

  • Kim, Seong-Hun;Kwon, Oh-Suk;Oh, Doo-Byoung
    • Journal of Plant Biotechnology
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    • v.37 no.3
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    • pp.292-304
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    • 2010
  • High value-added therapeutic proteins have been leading the biologics industry and occupied major portion of the market. More than 60% of the currently available protein therapeutics are glycoproteins attached with glycans which play crucial roles for the protein folding, therapeutic efficacy, in vivo half-life and immunogenecity. This review introduces the process of glycosylation and the impacts of glycans in the aspects of therapeutics. The important glycan structures in therapeutic performances were also summarized focusing on three representative categories of glycoproteins, cytokines, therapeutic antibody and enzyme. Currently, mammalian expression systems such as Chinese hamster ovary cells are preferred for the production of therapeutic glycoproteins due to their ability to synthesize glycans having similar structures with human type glycans. However, recent advances of plant glycoengineering to overcome the limitation originating from different glycan structures will soon allow to develop more efficient and economic plant-based production systems for therapeutic glycoproteins.

Simultaneous Determination of Valproic Acid and its Toxic Metabolites, 4-ene-VPA and 2,4-diene-VPA in Rat Plasma using a Gas Chromatographic-mass Spectrometric Method

  • Lee, Min-Sun;Lee, Young-Joo;Chung, Bong-Chul;Jung, Byung-Hwa
    • Journal of Pharmaceutical Investigation
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    • v.40 no.3
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    • pp.155-160
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    • 2010
  • A gas chromatographic-mass spectrometric (GC-MS) method was developed for the simultaneous determination of valproic acid (VPA) and its toxic metabolites, 4-ene-VPA and 2,4-diene-VPA in rat plasma. Extraction was performed in weak acidic condition (pH 5.2) to avoid degradation of 4-ene-VPA and 2,4-diene-VPA. The recoveries for 4-ene-VPA and 2,4-diene-VPA were more than 70% and that for VPA was 33-42%. R value for each compounds exceeded 0.998 in calibration curve during all the analysis. Accuracy and precision ranged from 88.3 to 113.2% and from 2.16 to 14.2%, respectively The method was successfully applied to monitor plasma concentrations of VPA, 4-ene-VPA and 2,4-diene-VPA after intravenous administration of VPA at the dose of 100 mg/kg, suggesting that these toxic metabolites may involved in the hepatotoxicity induced by VPA.

Characterization of Molecular Composition of Bacterial Melanin Isolated from Streptomyces glaucescens Using Ultra-High-Resolution FT-ICR Mass Spectrometry

  • Choi, Mira;Choi, A Young;Ahn, Soo-Yeon;Choi, Kwon-Young;Jang, Kyoung-Soon
    • Mass Spectrometry Letters
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    • v.9 no.3
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    • pp.81-85
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    • 2018
  • In this study, the chemical composition of bacterial melanin isolated from the Streptomyces glaucescens strain was elucidated by ultra-high-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. Ultra-high-resolution mass profiles of the microbial melanin product were acquired using a 15 Tesla FT-ICR mass spectrometer in positive and negative ion modes via electrospray ionization to obtain more complete descriptions of the molecular compositions of melanin-derived organic constituents. A mass resolving power of 500,000 (at m/z 400) was achieved for all spectra while collecting 400 scans per sample with a 4 M transient. The results of this analysis revealed that the melanin pigment isolated from S. glaucescens predominantly exhibits CHON and CHO species, which belong to the proteins class of compounds, with the mean C/O and C/N ratios of 4.3 and 13.1, thus suggesting that the melanin could be eumelanin. This analytical approach could be utilized to investigate the molecular compositions of a variety of natural or synthetic melanins. The compositional features of melanins are important for understanding their formation mechanisms and physico-chemical properties.

Set Covering-based Feature Selection of Large-scale Omics Data (Set Covering 기반의 대용량 오믹스데이터 특징변수 추출기법)

  • Ma, Zhengyu;Yan, Kedong;Kim, Kwangsoo;Ryoo, Hong Seo
    • Journal of the Korean Operations Research and Management Science Society
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    • v.39 no.4
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    • pp.75-84
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    • 2014
  • In this paper, we dealt with feature selection problem of large-scale and high-dimensional biological data such as omics data. For this problem, most of the previous approaches used simple score function to reduce the number of original variables and selected features from the small number of remained variables. In the case of methods that do not rely on filtering techniques, they do not consider the interactions between the variables, or generate approximate solutions to the simplified problem. Unlike them, by combining set covering and clustering techniques, we developed a new method that could deal with total number of variables and consider the combinatorial effects of variables for selecting good features. To demonstrate the efficacy and effectiveness of the method, we downloaded gene expression datasets from TCGA (The Cancer Genome Atlas) and compared our method with other algorithms including WEKA embeded feature selection algorithms. In the experimental results, we showed that our method could select high quality features for constructing more accurate classifiers than other feature selection algorithms.

Mutation of the lbp-5 gene alters metabolic output in Caenorhabditis elegans

  • Xu, Mo;Choi, Eun-Young;Paik, Young-Ki
    • BMB Reports
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    • v.47 no.1
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    • pp.15-20
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    • 2014
  • Intracellular lipid-binding proteins (LBPs) impact fatty acid homeostasis in various ways, including fatty acid transport into mitochondria. However, the physiological consequences caused by mutations in genes encoding LBPs remain largely uncharacterized. Here, we explore the metabolic consequences of lbp-5 gene deficiency in terms of energy homeostasis in Caenorhabditis elegans. In addition to increased fat storage, which has previously been reported, deletion of lbp-5 attenuated mitochondrial membrane potential and increased reactive oxygen species levels. Biochemical measurement coupled to proteomic analysis of the lbp-5(tm1618) mutant revealed highly increased rates of glycolysis in this mutant. These differential expression profile data support a novel metabolic adaptation of C. elegans, in which glycolysis is activated to compensate for the energy shortage due to the insufficient mitochondrial ${\beta}$-oxidation of fatty acids in lbp-5 mutant worms. This report marks the first demonstration of a unique metabolic adaptation that is a consequence of LBP-5 deficiency in C. elegans.

Secondary structure of the Irf7 5'-UTR, analyzed using SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension)

  • Kim, Yun-Mi;Choi, Won-Young;Oh, Chang-Mok;Han, Gyoon-Hee;Kim, Young-Joon
    • BMB Reports
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    • v.47 no.10
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    • pp.558-562
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    • 2014
  • OASL1 is a member of the 2'-5'-oligoadenylate synthetase (OAS) family and promotes viral clearance by activating RNase L. OASL1 interacts with the 5'-untranslated region (UTR) of interferon regulatory factor 7 (Irf7) and inhibits its translation. To identify the secondary structure required for OASL1 binding, we examined the 5'-UTR of the Irf7 transcript using "selective 2'-hydroxyl acylation analyzed by primer extension" (SHAPE). SHAPE takes advantage of the selective acylation of residues in single-stranded regions by 1-methyl-7-nitroisatoic anhydride (1M7). We found five major acylation sites located in, or next to, predicted single-stranded regions of the Irf7 5'-UTR. These results demonstrate the involvement of the stem structure of the Irf7 5'-UTR in the regulation of Irf7 translation, mediated by OASL1.

Simultaneous Quantification of 13 Ginsenosides by LC-MS/MS and its Application in Diverse Ginseng Extracts

  • Jo, Jung Jae;Cho, Pil Joung;Lee, Sangkyu
    • Mass Spectrometry Letters
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    • v.9 no.2
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    • pp.41-45
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    • 2018
  • Ginseng (Panax ginseng Meyer) has been used as traditional herbal drug in Asian countries. Ginsenosides are major components having pharmacological and biological efficacy like anti-inflammatory, anti-diabetic and anti-tumor effects. To control the quality of the components in diverse ginseng products, we developed a new quantitative method using LC-MS/MS for 13 ginsenosides; Rb1, Rb2, Rc, Rd, Re, Rf, 20(S)-Rh1, 20(S)-Rh2, Rg1, 20(S)-Rg3, F1, F2, and compound K. This method was successfully validated for linearity, precision, and accuracy. This quantification method applied in four representative ginseng products; fresh ginseng powder, white ginseng powder, red ginseng extract powder, and red ginseng extract. Here the amounts of the 13 ginsenosides in the various type of ginseng samples could be analyzed simultaneously and expected to be suitable for quality control of ginseng products.

Performance Characteristic of the β-Human Chorionic Gonadotropin Assay on the Access 2 for Its Use in Doping Control

  • Kang, Min-Jung;Lee, Hye-Im;Shin, Sang-Mi;Yoo, Hye-Hyun;Kwon, Oh-Seung;Jin, Chang-Bae;Chung, Bong-Chul
    • Bulletin of the Korean Chemical Society
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    • v.31 no.10
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    • pp.2889-2892
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    • 2010
  • The objective of this study was to validate performance characteristics of the Access 2 (Beckman coulter) system for hCG assays for use as a confirmation test for doping control. The Access 2 assay was linear up to 500 IU/L. The correlation coefficient was higher than 0.999, and the sensitivity of the linearity was 0.82. There were no false positive or false negative cases. LOD was 0.59 IU/L. The method was robust when performed by different people. Repeatability and reproducibility were below 7%. We compared reproducibility and recoveries of Access 2 and Elecsys 2010. Access 2 demonstrated higher reproducibility than Elecsys 2010. Recoveries (accuracy) of Access 2 were between 85 and 105%. Recoveries for Elecsys 2010 were between 91 and 104%.