A study of transposable element-associated structural variations (TASVs) using a de novo-assembled Korean genome

Mun Seyoung,Kim Songmi,Lee Wooseok,Kang Keunsoo,Meyer Thomas J.,Han Bok-Ghee,Han Kyudong,김희수 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

Advances in next-generation sequencing (NGS) technology have made personal genome sequencing possible, and indeed, many individual human genomes have now been sequenced. Comparisons of these individual genomes have revealed substantial genomic differences between human populations as well as between individuals from closely related ethnic groups. Transposable elements (TEs) are known to be one of the major sources of these variations and act through various mechanisms, including de novo insertion, insertion-mediated deletion, and TE–TE recombination-mediated deletion. In this study, we carried out de novo whole-genome sequencing of one Korean individual (KPGP9) via multiple insert-size libraries. The de novo whole-genome assembly resulted in 31,305 scaffolds with a scaffold N50 size of 13.23 Mb. Furthermore, through computational data analysis and experimental verification, we revealed that 182 TE-associated structural variation (TASV) insertions and 89 TASV deletions contributed 64,232 bp in sequence gain and 82,772 bp in sequence loss, respectively, in the KPGP9 genome relative to the hg19 reference genome. We also verified structural differences associated with TASVs by comparative analysis with TASVs in recent genomes (AK1 and TCGA genomes) and reported their details. Here, we constructed a new Korean de novo whole-genome assembly and provide the first study, to our knowledge, focused on the identification of TASVs in an individual Korean genome. Our findings again highlight the role of TEs as a major driver of structural variations in human individual genomes.

Phylogeny of Flavobacteria Group Isolated from Freshwater Using Multilocus Sequencing Analysis

Mun, Seyoung,Lee, Jungnam,Lee, Siwon,Han, Kyudong,Ahn, Tae-Young Korea Genome Organization 2013 Genomics & informatics Vol.11 No.4

Sequence analysis of the 16S rRNA gene has been widely used for the classification of microorganisms. However, we have been unable to clearly identify five Flavobacterium species isolated from a freshwater by using the gene as a single marker, because the evolutionary history is incomplete and the pace of DNA substitutions is relatively rapid in the bacteria. In this study, we tried to classify Flavobacterium species through multilocus sequence analysis (MLSA), which is a practical and reliable technique for the identification or classification of bacteria. The five Flavobacterium species isolated from freshwater and 37 other strains were classified based on six housekeeping genes: gyrB, dnaK, tuf, murG, atpA, and glyA. The genes were amplified by PCR and subjected to DNA sequencing. Based on the combined DNA sequence (4,412 bp) of the six housekeeping genes, we analyzed the phylogenetic relationship among the Flavobacterium species. The results indicated that MLSA, based on the six housekeeping genes, is a trustworthy method for the identification of closely related Flavobacterium species.

Novel Discovery of LINE-1 in a Korean Individual by a Target Enrichment Method

Shin, Wonseok,Mun, Seyoung,Kim, Junse,Lee, Wooseok,Park, Dong-Guk,Choi, Seungkyu,Lee, Tae Yoon,Cha, Seunghee,Han, Kyudong Korean Society for Molecular and Cellular Biology 2019 Molecules and cells Vol.42 No.1

Long interspersed element-1 (LINE-1 or L1) is an autonomous retrotransposon, which is capable of inserting into a new region of genome. Previous studies have reported that these elements lead to genomic variations and altered functions by affecting gene expression and genetic networks. Mounting evidence strongly indicates that genetic diseases or various cancers can occur as a result of retrotransposition events that involve L1s. Therefore, the development of methodologies to study the structural variations and interpersonal insertion polymorphisms by L1 element-associated changes in an individual genome is invaluable. In this study, we applied a systematic approach to identify human-specific L1s (i.e., L1Hs) through the bioinformatics analysis of high-throughput next-generation sequencing data. We identified 525 candidates that could be inferred to carry non-reference L1Hs in a Korean individual genome (KPGP9). Among them, we randomly selected 40 candidates and validated that approximately 92.5% of non-reference L1Hs were inserted into a KPGP9 genome. In addition, unlike conventional methods, our relatively simple and expedited approach was highly reproducible in confirming the L1 insertions. Taken together, our findings strongly support that the identification of non-reference L1Hs by our novel target enrichment method demonstrates its future application to genomic variation studies on the risk of cancer and genetic disorders.

Targeted exome sequencing to investigate horse temperament

Soyoung Song,Seyoung Mun,Wonseok Shin,Kyudong Han,Yongsoo Park 한국수정란이식학회 2017 한국수정란이식학회 학술대회 Vol.2017 No.05

Several studies on the correlation between temperament and genetic diversity are conducted in animals as well as human. Horse temperament is especially important because it is important factor for horse riding and racing. In this study, we performed targeted exome sequencing to find single nucleotide polymorphisms (SNPs) served as genetic markers that can evaluate the aggressive and docile levels of horses. We selected 71 candidate genes related to animal and human temperament through previous researches and verified it on the human reference genome (hg38) and horse reference genome (equCab2). We found that 16 orthologous genes were present in horse reference genome and 17 homologous genes found in horses based on the human reference genome. Finally, we designed probes to find the genetic variation in selected 33 genes. The sequencing libraries were constructed using the designed probe and DNA samples extracted from the blood of 8 aggressive and 8 docile horses. The constructed libraries were sequenced using the Illumina Hiseq2500 platform. SNPs data obtained from targeted exome sequencing will be used for genome wide association study (GWAS) and Sanger sequencing validation. This study will help to assess the horse temperament and to select superior horses for riding or racing.

Application of NanoString technologies in angioimmunoblastic T-cell lymphoma

Wonseok Shin,Seyoung Mun,Seungkyu Choi,Kyudong Han 한국유전학회 2020 Genes & Genomics Vol.42 No.4

Background Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive disease. Most cancer diagnoses are determined by anatomical histology. Therefore, many samples are stored in FFPE blocks for H&E staining. However, RNAs extracted from the FFPE block have a high level of fragmentation, making it difficult to perform accurate DEG analysis using RNA sequencing. Objective To overcome fragmented RNA’s drawback in NGS application, we applied the NanoString nCounter® technique of hybridization method that can be used for DEG analysis without PCR amplification. Methods We characterized the gene expression profiling of AITLs though transcriptome analysis based on the nCounter® PanCancer IO 360™ Panel and NanoString platform. To perform the analysis of differential expression gene (DEG) profiles in AITLs, we compared the NanoString data from eight AITL patients with a healthy control donor. Results Ninety-one genes were up-regulated and six genes were down-regulated in AITLs compared to control. The Gene Ontology (GO) analysis of 97-DEGs revealed that they were closely related to cytokine, MAPK cascade, leukocyte differentiation, and immune response, suggesting that this affect the immune system. In addition, KEGG analysis revealed that AITL DEGs were found to be highly involved in cytokine–cytokine receptor interaction and PI3K-Akt signaling pathway. Conclusion We believe that comprehensive multiplex studies, along with NanoString analysis, may be helpful to understand the molecular mechanisms of AITL, including mutations, gene expression, and protein expression studies.

The whole-genome and transcriptome of the manila clam (Ruditapes philippinarum)

Ha Yeun Song,Seyoung Mun,Young Se Hyun,Kyudong Han,Hye Suck An 한국수산해양기술학회(구 한국어업기술학회) 2017 한국수산해양기술학회 학술발표대회 Vol.2017 No.11

The inflammatory signature in monocytes of Sjögren’s syndrome and systemic lupus erythematosus, revealed by the integrated Reactome and drug target analysis

Lee Kyung Eun,Mun Seyoung,Kim Song-mi,Shin Wonseok,Jung Won,Paek Joon,Lee Jungnam,Hudson Erin,Reeves Wesley H.,Han Kyudong,Cha Seunghee 한국유전학회 2022 Genes & Genomics Vol.44 No.10

Background: The innate immune regulation, especially by the type I IFN signature in the CD14+ monocytes, is known to be critical in the pathogenesis of autoimmune Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE). Objective: Since patients with one condition can be overlapped with another, this study is to identify shared differentially expressed genes (DEGs) in SjS and SLE compared to healthy controls (HCs) and refine transcriptomic profiles with the integrated Reactome and gene-drug network analysis for an anti-inflammation therapy. Methods: CD14+ monocytes were purified from whole blood of SjS and SLE patients (females, ages from 32 to 62) and subject to bulk RNA-sequencing, followed by data analyses for comparison with HC monocytes (females, ages 30 and 33). Functional categorizations, using Gene Ontology (GO) and the Reactome pathway analysis, were performed and DEGs associated with therapeutic drugs were identified from the Drug Repurposing Hub (DHUB) database. Results: The GO analysis revealed that DEGs in the inflammatory response and the cellular response to cytokine were highly enriched in both conditions. A propensity toward M1 macrophage differentiation appears to be prominent in SjS while the Response to Virus was significant in SLE monocytes. Through the Reactome pathway analysis, DEGs in the IFN signaling and the cytokine signaling in immune system were most significantly enriched in both. Upregulation of NGF-induced transcription activity in SjS and the complement cascade activity in SLE were also noted. Multiple anti-inflammatory drugs, such as prostaglandin-endoperoxide synthase and angiotensin-I-converting- enzyme were associated with the DEGs in these conditions. Conclusions: Taken together, our analysis indicates distinct inflammatory transcriptomic profiles shared in SjS and SLE monocytes. Comprehensive characterizations of the data from these conditions will ultimately allow differential diagnosis of each condition and identification of therapeutic targets.

A rhodamine based fluorescent probe validates substrate and cellular hypoxia specific NADH expression

Podder, Arup,Koo, Seyoung,Lee, Jiyeong,Mun, Sora,Khatun, Sabina,Kang, Hee-Gyoo,Bhuniya, Sankarprasad,Kim, Jong Seung The Royal Society of Chemistry 2019 Chemical communications Vol.55 No.4

<P>Herein, we report a rhodamine-based redox probe (MQR) to visualize cytosolic NADH in the cellular milieu. Its high sensitivity and selectivity allowed it to track the alteration of the NADH level under metabolic perturbation, suggesting its potential as a useful tool to study the association between the NADH level and metabolic abnormalities with clinical significance.</P>

Optimal investment with time-varying transition probabilities for regime switching

( Hyo-chan Lee ),( Seyoung Park ),( Jong Mun Yoon ) 한국파생상품학회(구 한국선물학회) 2021 선물연구 Vol.29 No.2

This study aims to generalize the following result of McDonald and Siegel (1986) on optimal investment: it is optimal for an investor to invest when project cash flows exceed a certain threshold. This study presents other results that refine or extend this one by integrating timing flexibility and changes in cash flows with time-varying transition probabilities for regime switching. This study emphasizes that optimal thresholds are either overvalued or undervalued in the absence of time-varying transition probabilities. Accordingly, the stochastic nature of transition probabilities has important implications to the search for optimal timing of investment.

Identification and characterization of Acinetobacter nosocomialis BfmRS, two-component regulatory system, essential for biofilm development

Choi Chul Hee,Mun Seyoung,Oh Man Hwan 한국유전학회 2024 Genes & Genomics Vol.46 No.5

Background Biofilm development by bacteria is considered to be an essential stage in the bacterial infection. Acinetobacter nosocomialis is an important nosocomial pathogen causing a variety of human infections. However, characteristics and specific determinants of biofilm development have been poorly characterized in A. nosocomialis. Objective The aim of this study was to investigate the factors involved in the biofilm development by A. nosocomialis. Methods Library of random transposon mutants was constructed using the Tn5 mutagenesis. The mutant strains, in which the ability of biofilm formation was significantly impaired, were screened by gentian violet staining. The roles of BfmR and BfmS were determined by constructing a bfmR and bfmS deletion mutant and analyzing the effects of bfmR and bfmS mutation on the biofilm development and motility of A. nosocomialis. Results We identified a biofilm-defective mutant in which a transposon insertion inactivated an open reading frame encoding the BfmR in a two-component regulatory system consisting of BfmR and BfmS. The bfmR mutant revealed a significant reduction in biofilm formation and motility compared to wild-type strain. Deficiency in the biofilm formation and motility of the bfmR mutant was restored by single copy bfmR complementation. In contrast, the bfmS mutant had no effect on biofilm formation. Conclusion A. nosocomialis has a two-component regulatory system, BfmRS. BfmR is a response regulator required for the initial attachment and maturation of biofilm during the biofilm development as well as the bacterial growth. BfmR could be a potential drug target for A. nosocomialis infection. Background Biofilm development by bacteria is considered to be an essential stage in the bacterial infection. Acinetobacter nosocomialis is an important nosocomial pathogen causing a variety of human infections. However, characteristics and specific determinants of biofilm development have been poorly characterized in A. nosocomialis. Objective The aim of this study was to investigate the factors involved in the biofilm development by A. nosocomialis. Methods Library of random transposon mutants was constructed using the Tn5 mutagenesis. The mutant strains, in which the ability of biofilm formation was significantly impaired, were screened by gentian violet staining. The roles of BfmR and BfmS were determined by constructing a bfmR and bfmS deletion mutant and analyzing the effects of bfmR and bfmS mutation on the biofilm development and motility of A. nosocomialis. Results We identified a biofilm-defective mutant in which a transposon insertion inactivated an open reading frame encoding the BfmR in a two-component regulatory system consisting of BfmR and BfmS. The bfmR mutant revealed a significant reduction in biofilm formation and motility compared to wild-type strain. Deficiency in the biofilm formation and motility of the bfmR mutant was restored by single copy bfmR complementation. In contrast, the bfmS mutant had no effect on biofilm formation. Conclusion A. nosocomialis has a two-component regulatory system, BfmRS. BfmR is a response regulator required for the initial attachment and maturation of biofilm during the biofilm development as well as the bacterial growth. BfmR could be a potential drug target for A. nosocomialis infection.