Development of the variant calling algorithm, ADIScan, and its use to estimate discordant sequences between monozygotic twins

Cho, Yangrae,Lee, Sunho,Hong, Jong Hui,Kim, Byong Joon,Hong, Woon-Young,Jung, Jongcheol,Lee, Hyang Burm,Sung, Joohon,Kim, Han-Na,Kim, Hyung-Lae,Jung, Jongsun Oxford University Press 2018 Nucleic acids research Vol.46 No.15

<P><B>Abstract</B></P><P>Calling variants from next-generation sequencing (NGS) data or discovering discordant sequences between two NGS data sets is challenging. We developed a computer algorithm, ADIScan1, to call variants by comparing the fractions of allelic reads in a tester to the universal reference genome. We then created ADIScan2 by modifying the algorithm to directly compare two sets of NGS data and predict discordant sequences between two testers. ADIScan1 detected >99.7% of variants called by GATK with an additional 724 393 SNVs. ADIScan2 identified ∼500 candidates of discordant sequences in each of two pairs of the monozygotic twins. About 200 of these candidates were included in the ∼2800 predicted by VarScan2. We verified 66 true discordant sequences among the candidates that ADIScan2 and VarScan2 exclusively predicted. ADIScan2 detected many discordant sequences overlooked by VarScan2 and Mutect, which specialize in detecting low frequency mutations in genetically heterogeneous cancerous tissues. Numbers of verified sequences alone were >5 times more than expected based on recently estimated mutation rates from whole genome sequences. Estimated post-zygotic mutation rates were 1.68 × 10<SUP>−7</SUP> in this study. ADIScan1 and 2 would complement existing tools in screening causative mutations of diverse genetic diseases and comparing two sets of genome sequences, respectively.</P>

국가 융합연구사업의 현황 및 연계성 분석

조양래(Yangrae Cho),양이석(Iesuk Yang),서용윤(Yongyoon Suh),전정환(Jeonghwan Jeon) 대한산업공학회 2015 대한산업공학회지 Vol.41 No.3

How the Necrotrophic Fungus <i>Alternaria brassicicola</i> Kills Plant Cells Remains an Enigma

AMERICAN SOCIETY OF MICROBIOLOGY 2015 EUKARYOTIC CELL Vol.14 No.4

<P><I>Alternaria</I> species are mainly saprophytic fungi, but some are plant pathogens. Seven pathotypes of <I>Alternaria alternata</I> use secondary metabolites of host-specific toxins as pathogenicity factors. These toxins kill host cells prior to colonization. Genes associated with toxin synthesis reside on conditionally dispensable chromosomes, supporting the notion that pathogenicity might have been acquired several times by <I>A. alternata</I>. <I>Alternaria brassicicola</I>, however, seems to employ a different mechanism. Evidence on the use of host-specific toxins as pathogenicity factors remains tenuous, even after a diligent search aided by full-genome sequencing and efficient reverse-genetics approaches. Similarly, no individual genes encoding lipases or cell wall-degrading enzymes have been identified as strong virulence factors, although these enzymes have been considered important for fungal pathogenesis. This review describes our current understanding of toxins, lipases, and cell wall-degrading enzymes and their roles in the pathogenesis of <I>A. brassicicola</I> compared to those of other pathogenic fungi. It also describes a set of genes that affect pathogenesis in <I>A. brassicicola</I>. They are involved in various cellular functions that are likely important in most organisms and probably indirectly associated with pathogenesis. Deletion or disruption of these genes results in weakly virulent strains that appear to be sensitive to the defense mechanisms of host plants. Finally, this review discusses the implications of a recent discovery of three important transcription factors associated with pathogenesis and the putative downstream genes that they regulate.</P>

The Effect of Elastic Tape on Lower Extremity Muscle Activity in Squats of Young Female Adults: A Cross-sectional Pilot Study

Namjeong Cho,Yangrae Kim 한국전문물리치료학회 2023 한국전문물리치료학회지 Vol.30 No.3

Background: In terms of physical performance, elastic tape (ET) is known to contribute to injury prevention and performance enhancement. Objects: This study aimed to compare and analyze the effect on lower extremity muscle activ-ity of young adult women with and without ET during squats. Methods: In this study, six healthy, young women were recruited as participants in a univer-sity laboratory. Participants were allocated to two groups of three after measuring muscle ac-tivity in a pre-test, and the experiment was conducted for a total of two weeks (two sessions). First, 10 half squats were taped once in the first week, and 10 half squats were performed without taping in the second week. The other group did this in reverse and measured muscle activity after the squat was over. Results: As a result of this study, there was no significant difference in the quadriceps with or without ET (Z = –0.11, p > 0.05). Similarly, no significant difference was found in hamstring (Z = –0.31, p > 0.05). Conclusion: No beneficial effect was found on changes in muscle activity following ET ap-plication during squats. Further studies require randomized controlled trials that increase the number of participants and the intensity of the intervention, and measure pain, function, and performance rather than muscle properties depending on the biomechanical lifting mecha-nism.

Investigating the possibility of applying a Pareto/NBD model to predict the future citation count of a patent

Changyong Lee,Yangrae Cho,Changho Son,Hyeonju Seol,Yongtae Park 대한산업공학회 2010 대한산업공학회 춘계학술대회논문집 Vol.2010 No.6

Investigating the possibility of applying a Pareto/NBD model to predict the future citation count of a patent

Changyong Lee,Yangrae Cho,Changho Son,Hyeonju Seol,Yongtae Park 한국경영과학회 2010 한국경영과학회 학술대회논문집 Vol.2010 No.6

펜던트형 오르간 악셀 페달 개발

김은식(Eunsik Kim),조양래(Yangrae Cho) 한국자동차공학회 2011 한국자동차공학회 부문종합 학술대회 Vol.2011 No.5

The pendent type organ accel pedal has many advantages over pendent accel pedal and box type organ accel pedal. In this paper, we focus on pendent type organ accel pedal design optimization for linearity sensor property and strength & crash performance and ease-to-install. And by the bench and vehicle testing, we proved our optimal design.

HLAscan: genotyping of the HLA region using next-generation sequencing data

Ka, Sojeong,Lee, Sunho,Hong, Jonghee,Cho, Yangrae,Sung, Joohon,Kim, Han-Na,Kim, Hyung-Lae,Jung, Jongsun BioMed Central 2017 BMC bioinformatics Vol.18 No.1

<P><B>Background</B></P><P>Several recent studies showed that next-generation sequencing (NGS)-based human leukocyte antigen (HLA) typing is a feasible and promising technique for variant calling of highly polymorphic regions. To date, however, no method with sufficient read depth has completely solved the allele phasing issue. In this study, we developed a new method (HLAscan) for HLA genotyping using NGS data.</P><P><B>Results</B></P><P>HLAscan performs alignment of reads to HLA sequences from the international ImMunoGeneTics project/human leukocyte antigen (IMGT/HLA) database. The distribution of aligned reads was used to calculate a score function to determine correctly phased alleles by progressively removing false-positive alleles. Comparative HLA typing tests using public datasets from the 1000 Genomes Project and the International HapMap Project demonstrated that HLAscan could perform HLA typing more accurately than previously reported NGS-based methods such as HLAreporter and PHLAT. In addition, the results of <I>HLA-A</I>, −<I>B</I>, and <I>-DRB1</I> typing by HLAscan using data generated by NextGen were identical to those obtained using a Sanger sequencing–based method. We also applied HLAscan to a family dataset with various coverage depths generated on the Illumina HiSeq X-TEN platform. HLAscan identified allele types of <I>HLA-A</I>, −<I>B</I>, −<I>C</I>, −<I>DQB1</I>, and <I>-DRB1</I> with 100% accuracy for sequences at ≥ 90× depth, and the overall accuracy was 96.9%.</P><P><B>Conclusions</B></P><P>HLAscan, an alignment-based program that takes read distribution into account to determine true allele types, outperformed previously developed HLA typing tools. Therefore, HLAscan can be reliably applied for determination of HLA type across the whole-genome, exome, and target sequences.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1186/s12859-017-1671-3) contains supplementary material, which is available to authorized users.</P>

Mechanism of the natural product moracin-O derived MO-460 and its targeting protein hnRNPA2B1 on HIF-1α inhibition

Soung, Nak-Kyun,Kim, Hye-Min,Asami, Yukihiro,Kim, Dong Hyun,Cho, Yangrae,Naik, Ravi,Jang, Yerin,Jang, Kusic,Han, Ho Jin,Ganipisetti, Srinivas Rao,Cha-Molstad, Hyunjoo,Hwang, Joonsung,Lee, Kyung Ho,Ko, Nature Publishing Group UK 2019 Experimental and molecular medicine Vol.51 No.2

<▼1><P>Hypoxia-inducible factor-1α (HIF-1α) mediates tumor cell adaptation to hypoxic conditions and is a potentially important anticancer therapeutic target. We previously developed a method for synthesizing a benzofuran-based natural product, (R)-(-)-moracin-O, and obtained a novel potent analog, MO-460 that suppresses the accumulation of HIF-1α in Hep3B cells. However, the molecular target and underlying mechanism of action of MO-460 remained unclear. In the current study, we identified heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) as a molecular target of MO-460. MO-460 inhibits the initiation of HIF-1α translation by binding to the C-terminal glycine-rich domain of hnRNPA2B1 and inhibiting its subsequent binding to the 3’-untranslated region of <I>HIF-1α</I> mRNA. Moreover, MO-460 suppresses HIF-1α protein synthesis under hypoxic conditions and induces the accumulation of stress granules. The data provided here suggest that hnRNPA2B1 serves as a crucial molecular target in hypoxia-induced tumor survival and thus offer an avenue for the development of novel anticancer therapies.</P></▼1><▼2><P><B>Cancer: How a plant metabolite analog suppresses tumor growth</B></P><P>A synthetic analog of a chemical found in fruit suppresses tumor growth by targeting an RNA-binding protein (hnRNPA2B1) and preventing the production of a pro-cancer regulatory factor. Nak-Kyun Soung from the Korea Research Institute of Bioscience and Biotechnology, Cheongju, South Korea, and coworkers built on their previous discovery that a compound derived from a medicinal plant metabolite can suppress the activity of hypoxia-inducible factor-1α (HIF-1α). This protein, which is involved in many aspects of cancer biology, is activated in the low-oxygen microenvironments found inside tumors. The researchers show that the compound binds to a protein that helps with the conversion of HIF-1α–encoding RNA transcripts into HIF-1α proteins. Liver cancer cells treated with the compound grew slowly and produced less HIF-1α under both normal and low-oxygen culture conditions, highlighting the potential of this anti-cancer strategy.</P></▼2>

At Death’s Door: Alternaria Pathogenicity Mechanisms

Christopher B. Lawrence,Thomas K. Mitchell,Kelly D. Craven,Yangrae Cho,Robert A. Cramer Jr,김광형 한국식물병리학회 2008 Plant Pathology Journal Vol.24 No.2

The fungal genus Alternaria is comprised of many saprophytic and endophytic species, but is most well known as containing many notoriously destructive plant pathogens. There are over 4,000 Alternaria/host associations recorded in the USDA Fungal Host Index ranking the genus 10th among nearly 2,000 fungal genera based on the total number of host records. While few Alternaria species appear to have a sexual stage to their life cycles, the majority lack sexuality altogether. Many pathogenic species of Alternaria are prolific toxin producers, which facilitates their necrotrophic lifestyle. Necrotrophs must kill host cells prior to colonization, and thus these toxins are secreted to facilitate host cell death often by triggering genetically programmed apoptotic pathways or by directly causing cell damage resulting in necrosis. While many species of Alternaria produce toxins with rather broad host ranges, a closelyrelated group of agronomically important Alternaria species produce selective toxins with a very narrow range often to the cultivar level. Genes that code for and direct the biosynthesis of these host-specific toxins for the Alternaria alternata sensu lato lineages are often contained on small, mostly conditionally dispensable, chromosomes. Besides the role of toxins in Alternaria pathogenesis, relatively few genes and/or gene products have been identified that contribute to or are required for pathogenicity. Recently, the completion of the A. brassicicola genome sequencing project has facilitated the examination of a substantial subset of genes for their role in pathogenicity. In this review, we will highlight the role of toxins in Alternaria pathogenesis and the use of A. brassicicola as a model representative for basic virulence studies for the genus as a whole. The current status of these research efforts will be discussed.