Genetic Landscape of Open Chromatin in Yeast

Lee, Kibaick,Kim, Sang Cheol,Jung, Inkyung,Kim, Kwoneel,Seo, Jungmin,Lee, Heun-Sik,Bogu, Gireesh K.,Kim, Dongsup,Lee, Sanghyuk,Lee, Byungwook,Choi, Jung Kyoon Public Library of Science 2013 PLoS genetics Vol.9 No.2

<▼1><P>Chromatin regulation underlies a variety of DNA metabolism processes, including transcription, recombination, repair, and replication. To perform a quantitative genetic analysis of chromatin accessibility, we obtained open chromatin profiles across 96 genetically different yeast strains by FAIRE (formaldehyde-assisted isolation of regulatory elements) assay followed by sequencing. While 5∼10% of open chromatin region (OCRs) were significantly affected by variations in their underlying DNA sequences, subtelomeric areas as well as gene-rich and gene-poor regions displayed high levels of sequence-independent variation. We performed quantitative trait loci (QTL) mapping using the FAIRE signal for each OCR as a quantitative trait. While individual OCRs were associated with a handful of specific genetic markers, gene expression levels were associated with many regulatory loci. We found multi-target <I>trans</I>-loci responsible for a very large number of OCRs, which seemed to reflect the widespread influence of certain chromatin regulators. Such regulatory hotspots were enriched for known regulatory functions, such as recombinational DNA repair, telomere replication, and general transcription control. The OCRs associated with these multi-target <I>trans</I>-loci coincided with recombination hotspots, telomeres, and gene-rich regions according to the function of the associated regulators. Our findings provide a global quantitative picture of the genetic architecture of chromatin regulation.</P></▼1><▼2><P><B>Author Summary</B></P><P>Quantitative trait loci (QTL) mapping is a genetic approach that allows the identification of genetic factors underlying a phenotype of interest. Genomic technologies such as DNA microarray and next-generation sequencing provide data that can be used for the analysis of multiple molecular phenotypes. For example, the expression levels of thousands of genes can be associated with subject-specific genome-wide genetic information in expression QTL mapping. Similarly, the genetic regulation of transcription factor binding or epigenetic mechanisms such as DNA methylation or chromatin structure has begun to be investigated. In particular, the mechanisms controlling chromatin accessibility have attracted special interest due to their importance in a variety of DNA regulation processes including recombination, repair, replication, and transcription. In this work, we sought to dissect the genetic architecture of chromatin accessibility regulation by harnessing the power of genetic and genomic techniques. By analyzing open (accessible) chromatin maps of multiple yeast individuals in association with their genetic backgrounds, we were able to characterize the regulatory structure of chromatin traits versus that of gene expression. Importantly, we observed that the genetic loci responsible for multiple open chromatin regions were enriched for known regulatory factors.</P></▼2>

Utilizing random Forest QSAR models with optimized parameters for target identification and its application to target-fishing server

Lee, Kyoungyeul,Lee, Minho,Kim, Dongsup BioMed Central 2017 BMC bioinformatics Vol.18 No.suppl16

<P><B>Background</B></P><P>The identification of target molecules is important for understanding the mechanism of “target deconvolution” in phenotypic screening and “polypharmacology” of drugs. Because conventional methods of identifying targets require time and cost, <I>in-silico</I> target identification has been considered an alternative solution. One of the well-known <I>in-silico</I> methods of identifying targets involves structure activity relationships (SARs). SARs have advantages such as low computational cost and high feasibility; however, the data dependency in the SAR approach causes imbalance of active data and ambiguity of inactive data throughout targets.</P><P><B>Results</B></P><P>We developed a ligand-based virtual screening model comprising 1121 target SAR models built using a random forest algorithm. The performance of each target model was tested by employing the ROC curve and the mean score using an internal five-fold cross validation. Moreover, recall rates for top-<I>k</I> targets were calculated to assess the performance of target ranking. A benchmark model using an optimized sampling method and parameters was examined via external validation set. The result shows recall rates of 67.6% and 73.9% for top-11 (1% of the total targets) and top-33, respectively. We provide a website for users to search the top-<I>k</I> targets for query ligands available publicly at http://rfqsar.kaist.ac.kr.</P><P><B>Conclusions</B></P><P>The target models that we built can be used for both predicting the activity of ligands toward each target and ranking candidate targets for a query ligand using a unified scoring scheme. The scores are additionally fitted to the probability so that users can estimate how likely a ligand–target interaction is active. The user interface of our web site is user friendly and intuitive, offering useful information and cross references.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (10.1186/s12859-017-1960-x) contains supplementary material, which is available to authorized users.</P>

Potential forensic application of receptor for advanced glycation end products (RAGE) and aquaporin 5 (AQP5) as novel biomarkers for diagnosis of drowning

Lee, So-Yeon,Ha, Eun-Ju,Cho, Hye-Won,Kim, Hye-Rim,Lee, Dongsup,Eom, Yong-Bin Elsevier 2019 Journal of forensic and legal medicine Vol.62 No.-

<P><B>Abstract</B></P> <P>Drowning is the most common cause of unnatural death worldwide. There is no single biomarker to diagnose drowning, so the diagnosis of drowning is one of the most difficult tasks in forensic medicine. Especially, distinguishing a victim of drowning from a body disposed of in water following death remains a problem. The objective of this study was to identify specific biomarkers of drowning compared with other causes of death such as hypoxia and postmortem submersion. The present study investigated the intrapulmonary expression of receptor for advanced glycation end products (RAGE), aquaporin-5 (AQP5), surfactant protein-A (SP-A), interleukin 6 (IL-6) and interleukin 1β (IL-1β) as markers of drowning. In animal experiments, all rats (n = 45) were classified into four groups (drowning, postmortem-submersion, hypoxia and control group). The lungs of experimental animals were analyzed as mRNA expression, immunoblot expression and immunohistochemical staining. qRT-PCR demonstrated increased mRNA expression of RAGE and AQP5 in drowning group compared with that in control, hypoxia and postmortem-submersion group, but not other molecules. Western blotting also showed high expression of RAGE and AQP5 in drowning group, immunostaining of RAGE and AQP5 was highly detected in a linear pattern in type I alveolar epithelial cells, compared with control and postmortem-submersion group. These observations indicate a difference of expression in pulmonary molecular pathology compared with other causes, suggesting RAGE and AQP5 may be useful for differentiation between drowning and postmortem-submersion.</P> <P><B>Highlights</B></P> <P> <UL> <LI> RAGE and AQP5 mRNA showed increased expression in drowning compared with postmortem-submersion. </LI> <LI> Western blotting and IHC staining analysis also showed high expression of RAGE and AQP5 in drowning group. </LI> <LI> RAGE and AQP5 can be helpful to differentiate drowning from postmortem-submersion. </LI> </UL> </P>

Prediction of protein secondary structure content using amino acid composition and evolutionary information

Lee, Soyoung,Lee, Byung-chul,Kim, Dongsup Wiley Subscription Services, Inc., A Wiley Company 2006 Proteins Vol.62 No.4

<P>Knowing protein structure and inferring its function from the structure are one of the main issues of computational structural biology, and often the first step is studying protein secondary structure. There have been many attempts to predict protein secondary structure contents. Previous attempts assumed that the content of protein secondary structure can be predicted successfully using the information on the amino acid composition of a protein. Recent methods achieved remarkable prediction accuracy by using the expanded composition information. The overall average error of the most successful method is 3.4%. Here, we demonstrate that even if we only use the simple amino acid composition information alone, it is possible to improve the prediction accuracy significantly if the evolutionary information is included. The idea is motivated by the observation that evolutionarily related proteins share the similar structure. After calculating the homolog-averaged amino acid composition of a protein, which can be easily obtained from the multiple sequence alignment by running PSI-BLAST, those 20 numbers are learned by a multiple linear regression, an artificial neural network and a support vector regression. The overall average error of method by a support vector regression is 3.3%. It is remarkable that we obtain the comparable accuracy without utilizing the expanded composition information such as pair-coupled amino acid composition. This work again demonstrates that the amino acid composition is a fundamental characteristic of a protein. It is anticipated that our novel idea can be applied to many areas of protein bioinformatics where the amino acid composition information is utilized, such as subcellular localization prediction, enzyme subclass prediction, domain boundary prediction, signal sequence prediction, and prediction of unfolded segment in a protein sequence, to name a few. Proteins 2006. © 2005 Wiley-Liss, Inc.</P>

Human Papillomavirus Distribution among Women in Western Shandong Province, East China using Reverse Blot Hybridization Assay

Dongsup Lee,Geehyuk Kim,Sunghyun Kim,Sunyoung Park,Hye-young Wang,Sangjung Park,Lin Han,Ren Yubo,Yingxue Li,Kwang Hwa Park,Hyeyoung Lee 대한의생명과학회 2015 Biomedical Science Letters Vol.21 No.2

Cervical cancer is the third most common cancer in women worldwide and there is a significant association between human papillomavirus (HPV) infection and cervical cancer. Certain HPV groups, labeled high-risk (HR) HPV groups, are strongly associated with malignancies of the human cervix. HPV prevalence and genotype distribution were analyzed using the REBA HPV-ID<SUP>®</SUP> (YD Diagnostics, Yongin, Korea) assay based on the reverse blot hybridization assay (REBA) with a total of 324 liquid-based cytology samples from women in Western Shandong Province, East China and results were compared with cytological diagnosis. Most of the HPV genotypes that were detected in high-grade cervical lesions were HR-HPV genotypes such as HPV 16, 18, 33, 53, and 58. The prevalence of these HR-HPV genotypes increased in high-grade cervical lesions. However, from low- to high-grade cervical lesions, the ability to detect LR-HPV genotypes decreased. Additionally, in general, the single HPV genotype infection rate increases in proportion to the severity of the lesion. The study findings suggest that a currently available preventive vaccine against HPV 16 and 18 may have limited effectiveness for prevention of all HPV infection in this province. Finally, based on these findings, these data could guide national or regional vaccination programs in the Western Shandong Province of East China to substantially reduce the burden of cervical lesions.

Effect of Extraction Ethanol Concentration on Antioxidant and Anti-Inflammatory Activity of 30-Year-Old and 120-Year-Old Dangyuja (Citrus maxima (Burm.) Merr.)

Lee, Sung-Gyu,Lee, Dongsup,Kang, Hyun The Korean Society for Biomedical Laboratory Scien 2020 Biomedical Science Letters Vol.26 No.2

Dangyuja (Citrus maxima (Burm.) Merr.) is a native fruit of great economic importance in Jeju island in Korea. To provide experimental evidence for the antioxidant and anti-inflammation properties on extraction ethanol concentration of Dangyuja, 2 cultivars, including 30-year-old and 120-year-old were evaluated. 30-year-old Dangyuja 50%, 70% ethanol extracts had the highest polyphenol and flavonoid content, and the strongest 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity. To investigate the anti-inflammatory activity of Dangyuja ethanol extracts, we used BV-2 microglia cells and induced inflammation using lipopolysaccharide (LPS). Then, we measured levels of inflammatory mediators as nitric oxide (NO). Among the 6 extracts, 30-year-old Dangyuja 50% ethanol extracts show the highest anti-inflammatory activity. The results suggest that 30-year-old Dangyuja 50% ethanol extracts provides significant health benefits and may be used for developing new functional materials.

Application of thermal field-flow fractionation/multi angle light scatteringand size-exclusion chromatography for analysis of emulsion styrene-butadiene rubber

Dongsup Song,Seyoung Yoon,Woonjung Kim,Seong Ho Choi,Seung Hwa Lee,A-Ju Kim,Seungho Lee 한국분석과학회 2018 학술대회논문집 Vol.2018 No.5

Study on the effect of capping agent molecular weight on silver nanoparticles using two field flow fractionation techniques

Dongsup Song,Jangjae Lee,Seungho Lee 한국분석과학회 2020 학술대회논문집 Vol.2020 No.6

A Novel Small Molecule Facilitates the Reprogramming of Human Somatic Cells into a Pluripotent State and Supports the Maintenance of an Undifferentiated State of Human Pluripotent Stem Cells

Lee, Jungwoon,Xia, Yan,Son, Mi‐,Young,Jin, Guanghai,Seol, Binna,Kim, Min‐,Jeong,Son, Myung Jin,Do, Misol,Lee, Minho,Kim, Dongsup,Lee, Kyeong,Cho, Yee Sook WILEY‐VCH Verlag 2012 Angewandte Chemie Vol.124 No.50

<P><B>Pluripotenz‐Booster</B>: RSC133, ein neues synthetisches Derivat von Indolacrylsäure/Indolpropionsäure, zeigt zweifache Aktivität, indem es Histondeacetylase und DNA‐Methyltransferase inhibiert. Außerdem verbessert es wirksam die Reprogrammierung von menschlichen somatischen Zellen in einen pluripotenten Zustand und unterstützt Wachstum und Erhaltung von humanen pluripotenten Stammzellen (hPSCs).</P>

Determination of new antifouling agents in seacoasts in Korea by gas chromatography-mass spectrometry

Seongeon Lee(이성언),Hoshik Won(원호식),Dongsup Lee(이동섭) 한국분석과학회 2008 분석과학 Vol.21 No.6