• 제목/요약/키워드: Chemical genomics

검색결과 146건 처리시간 0.025초

Genomewide Profiling of Rapamycin Sensitivity in Saccharomyces cerevisiae on Synthetic Medium

  • Chang, Yeon-Ji;Shin, Chun-Shik;Han, Dong-Hun;Kim, Ji-Yun;Kim, Kang-In;Kwon, Yong-Min;Huh, Won-Ki
    • Genomics & Informatics
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    • 제8권4호
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    • pp.177-184
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    • 2010
  • The target of rapamycin (TOR) signaling pathway is a conserved pathway that regulates eukaryotic cell growth in response to environmental cues. Chemical genomic approaches that profile rapamycin sensitivity of yeast deletion strains have given insights into the function of TOR signaling pathway. In the present study, we analyzed the rapamycin sensitivity of yeast deletion library strains on synthetic medium. As a result, we identified 130 strains that are hypersensitive or resistant to rapamycin compared with wild-type cells. Among them, 36 genes are newly identified to be related to rapamycin sensitivity. Moreover, we found 16 strains that show alteration in rapamycin sensitivity between complex and synthetic media. We suggest that these genes may be involved in part of TOR signaling activities that is differentially regulated by media composition.

Semantic Modeling for SNPs Associated with Ethnic Disparities in HapMap Samples

  • Kim, HyoYoung;Yoo, Won Gi;Park, Junhyung;Kim, Heebal;Kang, Byeong-Chul
    • Genomics & Informatics
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    • 제12권1호
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    • pp.35-41
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    • 2014
  • Single-nucleotide polymorphisms (SNPs) have been emerging out of the efforts to research human diseases and ethnic disparities. A semantic network is needed for in-depth understanding of the impacts of SNPs, because phenotypes are modulated by complex networks, including biochemical and physiological pathways. We identified ethnicity-specific SNPs by eliminating overlapped SNPs from HapMap samples, and the ethnicity-specific SNPs were mapped to the UCSC RefGene lists. Ethnicity-specific genes were identified as follows: 22 genes in the USA (CEU) individuals, 25 genes in the Japanese (JPT) individuals, and 332 genes in the African (YRI) individuals. To analyze the biologically functional implications for ethnicity-specific SNPs, we focused on constructing a semantic network model. Entities for the network represented by "Gene," "Pathway," "Disease," "Chemical," "Drug," "ClinicalTrials," "SNP," and relationships between entity-entity were obtained through curation. Our semantic modeling for ethnicity-specific SNPs showed interesting results in the three categories, including three diseases ("AIDS-associated nephropathy," "Hypertension," and "Pelvic infection"), one drug ("Methylphenidate"), and five pathways ("Hemostasis," "Systemic lupus erythematosus," "Prostate cancer," "Hepatitis C virus," and "Rheumatoid arthritis"). We found ethnicity-specific genes using the semantic modeling, and the majority of our findings was consistent with the previous studies - that an understanding of genetic variability explained ethnicity-specific disparities.

Mainchain NMR Assignments and secondary structure prediction of the C-terminal domain of BldD, a developmental transcriptional regulator from Streptomyces coelicolor A3(2)

  • Kim, Jeong-Mok;Won, Hyung-Sik;Kang, Sa-Ouk
    • 한국자기공명학회논문지
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    • 제17권1호
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    • pp.59-66
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    • 2013
  • BldD, a developmental transcription factor from Streptomyces coelicolor, is a homodimeric, DNA-binding protein with 167 amino acids in each subunit. Each monomer consists of two structurally distinct domains, the N-terminal domain (BldD-NTD) responsible for DNA-binding and dimerization and the C-terminal domain (BldD-CTD). In contrast to the BldD-NTD, of which crystal structure has been solved, the BldD-CTD has been characterized neither in structure nor in function. Thus, in terms of structural genomics, structural study of the BldD-CTD has been conducted in solution, and in the present work, mainchain NMR assignments of the recombinant BldD-CTD (residues 80-167 of BldD) could be achieved by a series of heteronuclear multidimensional NMR experiments on a [$^{13}C/^{15}N$]-enriched protein sample. Finally, the secondary structure prediction by CSI and TALOS+ analysis using the assigned chemical shifts data identified a ${\beta}-{\alpha}-{\alpha}-{\beta}-{\alpha}-{\alpha}-{\alpha}$ topology of the domain. The results will provide the most fundamental data for more detailed approach to the atomic structure of the BldD-CTD, which would be essential for entire understanding of the molecular function of BldD.

HP0902 from Helicobacter pylori is a thermostable, dimeric protein belonging to an all-β topology of the cupin superfamily

  • Sim, Dae-Won;Lee, Yoo-Sup;Kim, Ji-Hun;Seo, Min-Duk;Lee, Bong-Jin;Won, Hyung-Sik
    • BMB Reports
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    • 제42권6호
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    • pp.387-392
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    • 2009
  • Here, we report the first biochemical and structural characterization of the hypothetical protein HP0902 from Helicobacter pylori, in terms of structural genomics. Gel-permeation chromatography and dynamic light scattering indicated that the protein behaves as a dimer in solution. Circular dichroism spectroscopy showed that HP0902 primarily adopts a $\beta$-structure and the protein was highly thermostable with a denaturing temperature higher than $70^{\circ}C$. Finally, the backbone NMR assignments were obtained on the [$^{13}C,^{15}N$]HP0902 and the secondary structure was determined using the chemical shift data. Additionally, the local flexibility was assessed via a heteronuclear $^1H-^{15}N$ steady state NOE experiment. The results revealed that HP0902 would adopt a compactly folded, all-$\beta$ topology with 11 $\beta$-strands. All of the results clearly support the notion that HP0902 belongs to the cupin superfamily of proteins.

Computational Chemistry as a Key to Structural Bioinformatics

  • Kang, Young-Kee
    • 한국생물정보학회:학술대회논문집
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    • 한국생물정보시스템생물학회 2000년도 International Symposium on Bioinformatics
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    • pp.32-34
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    • 2000
  • Computational chemistry is a discipline using computational methods for the calculation of molecular structure, properties, and reaction or for the simulation of molecular behavior. Relating and turning the complexity of data from genomics, high-throughput screening, combinatorial chemical synthesis, gene-expression investigations, pharmacogenomics, and proteomics into useful information and knowledge is the primary goal of bioinformatics. In particular, the structure-based molecular design is one of essential fields in bioinformatics and it can be called as structural bioinformatics. Therefore, the conformational analysis for proteins and peptides using the techniques of computational chemistry is expected to play a role in structural bioinformatics. There are two major computational methods for conformational analysis of proteins and peptides; one is the molecular orbital (MO) method and the other is the force field (or empirical potential function) method. The MO method can be classified into ab initio and semiempirical methods, which have been applied to relatively small and large molecules, respectively. However, the improvement in computer hardwares and softwares enables us to use the ab initio MO method for relatively larger biomolecules with up to v100 atoms or ∼800 basis functions. In order to show how computational chemistry can be used in structural bioinformatics, 1 will present on (1) cis-trans isomerization of proline dipeptide and its derivatives, (2) positional preference of proline in ${\alpha}$-helices, and (3) conformations and activities of Arg-Gly-Asp-containing tetrapeptides.

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Comparative study: nonsynonymous and synonymous substitution of SARS-CoV-2, SARS-CoV, and MERS-CoV genome

  • Sohpal, Vipan Kumar
    • Genomics & Informatics
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    • 제19권2호
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    • pp.15.1-15.7
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    • 2021
  • The direction of evolution can estimate based on the variation among nonsynonymous to synonymous substitution. The simulative study investigated the nucleotide sequence of closely related strains of respiratory syndrome viruses, codon-by-codon with maximum likelihood analysis, z selection, and the divergence time. The simulated results, dN/dS > 1 signify that an entire substitution model tends towards the hypothesis's positive evolution. The effect of transition/transversion proportion, Z-test of selection, and the evolution associated with these respiratory syndromes, are also analyzed. Z-test of selection for neutral and positive evolution indicates lower to positive values of dN-dS (0.012, 0.019) due to multiple substitutions in a short span. Modified Nei-Gojobori (P) statistical technique results also favor multiple substitutions with the transition/transversion rate from 1 to 7. The divergence time analysis also supports the result of dN/dS and imparts substantiating proof of evolution. Results conclude that a positive evolution model, higher dN-dS, and transition/transversion ratio significantly analyzes the evolution trend of severe acute respiratory syndrome coronavirus 2, severe acute respiratory syndrome coronavirus, and Middle East respiratory syndrome coronavirus.

Computational analysis of SARS-CoV-2, SARS-CoV, and MERS-CoV genome using MEGA

  • Sohpal, Vipan Kumar
    • Genomics & Informatics
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    • 제18권3호
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    • pp.30.1-30.7
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    • 2020
  • The novel coronavirus pandemic that has originated from China and spread throughout the world in three months. Genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) predecessor, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) play an important role in understanding the concept of genetic variation. In this paper, the genomic data accessed from National Center for Biotechnology Information (NCBI) through Molecular Evolutionary Genetic Analysis (MEGA) for statistical analysis. Firstly, the Bayesian information criterion (BIC) and Akaike information criterion (AICc) are used to evaluate the best substitution pattern. Secondly, the maximum likelihood method used to estimate of transition/transversions (R) through Kimura-2, Tamura-3, Hasegawa-Kishino-Yano, and Tamura-Nei nucleotide substitutions model. Thirdly and finally nucleotide frequencies computed based on genomic data of NCBI. The results indicate that general times reversible model has the lowest BIC and AICc score 347,394 and 347,287, respectively. The transition/transversions bias for nucleotide substitutions models varies from 0.56 to 0.59 in MEGA output. The average nitrogenous bases frequency of U, C, A, and G are 31.74, 19.48, 28.04, and 20.74, respectively in percentages. Overall the genomic data analysis of SARS-CoV-2, SARS-CoV, and MERS-CoV highlights the close genetic relationship.

Identification of pathways and genes associated with cerebral palsy

  • Zhu, Qingwen;Ni, Yufei;Wang, Jing;Yin, Honggang;Zhang, Qin;Zhang, Lingli;Bian, Wenjun;Liang, Bo;Kong, Lingyin;Xuan, Liming;Lu, Naru
    • Genes and Genomics
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    • 제40권12호
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    • pp.1339-1349
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    • 2018
  • Cerebral palsy (CP) is a non-progressive neurological disease, of which susceptibility is linked to genetic and environmental risk factors. More and more studies have shown that CP might be caused by multiple genetic factors, similar to other neurodevelopmental disorders. Due to the high genetic heterogeneity of CP, we focused on investigating related molecular pathways. Ten children with CP were collected for whole-exome sequencing by next-generation sequencing (NGS) technology. Customized processes were used to identify potential pathogenic pathways and variants. Three pathways (axon guidance, transmission across chemical synapses, protein-protein interactions at synapses) with twenty-three genes were identified to be highly correlated with CP. This study showed that the three pathways associated with CP might be the molecular mechanism of pathogenesis. These findings could provide useful clues for developing pathway-based pharmacotherapies. Further studies are required to confirm potential roles for these pathways in the pathogenesis of CP.

A review of the latest research on Ganoderma boninense

  • Su-Han LEE;Su-Han LEE
    • 식품보건융합연구
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    • 제9권2호
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    • pp.1-6
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    • 2023
  • As oil palm trees are an important economic source in many countries, particularly in Southeast Asia and Africa, the study of Ganoderma boninense is crucial for the sustainability of the oil palm industry. This study aims to understand the biology and ecology of the fungus, its pathogenesis, and the impact it has on oil palm trees. This knowledge can be used to develop management strategies to mitigate the damage caused by the fungus, such as the use of resistant varieties, chemical and biological control methods, and cultural practices. This study is to ensure the long-term productivity and sustainability of the oil palm industry. The main method of recent academic studies on this pathogen is molecular biology, with a focus on genetic analysis and functional genomics. Researchers have used techniques such as PCR, DNA sequencing, and transcriptomics to identify genes and pathways involved in pathogenesis and better understand the fungus's interactions with its host plant. Other methods used in recent studies include biochemical analysis, microscopy, and phytohormonal assays to investigate the biochemistry and physiology of the interaction between G. boninense and oil palm. This study is intended to provide implications from a new perspective by organizing and integrating studies on Ganoderma boninense.

The Variation of Yield-Related Traits of the QTL Pyramiding Lines for Climate-resilience and Nutrition Uptake in Rice

  • Joong Hyoun Chin
    • 한국작물학회:학술대회논문집
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    • 한국작물학회 2022년도 추계학술대회
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    • pp.14-14
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    • 2022
  • Greenhouse gas emissions are one of the critical factors that drive change in rice cropping systems. Within this changing system, less water irrigation and chemical fertilizer are seriously considered, as well combining precision farming technologies with irrigation control. Water and phosphorus (P) fertilizer are two of the most critical inputs in rice cultivation. Due to the lack of water availability in the system, P fertilizer is not available, especially in acidic soil conditions. Moreover, the various types of abiotic stresses, such as drought, high temperature, salinity, submergence, and limited fertilizer result in significant yield loss in the system. Even in the late stage of growth, the waves caused by diseases and insects make the field more unfruitful. Therefore, agronomists and breeders need to identify the secondary phenotypes to estimate the yield loss of when stress appears. The prediction will be clearer if we have a set of markers tagging the causal variation and the associated precise phenotype indices. Although there have been various studies for abiotic stress tolerance, we still lack functional molecular markers and phenotype indices. This is due to the underlying challenges caused by environmental factors in highly unpredictable regional and yearly environmental conditions in the field system. Pupl (phosphorus uptake 1) is still known as the first QTL associated with phosphorus uptake and have been validated in different field crops. Interestingly, some pyramiding lines of Pupl and other QTLs for other stress tolerances showed preferable phenotypes in the yield. Precise physiological studies with the help of genomics are on-going and some results will be discussed.

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