• 제목/요약/키워드: Gene Modeling

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In Silico Study of Human Gap Junction Beta-2 Protein by Homology Modeling

  • Shehzadi, Abida;Masood, Khalid
    • Genomics & Informatics
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    • 제8권2호
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    • pp.70-75
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    • 2010
  • Asp66his, Asp54Lys, and Asp50Asn are mutations in connexin 26 that are observed in the clinic and give rise to autosomal dominant syndromes. They are the result of point mutations in the human gap junction ${\beta}-2$ gene. In order to investigate the structural mechanism of Bart-Pumphrey Syndrome, Keratitis-Ichthyosis-Deafness Syndrome, and Vohwinkel Syndrome, homology modeling was carried out. Asp66 has direct contact with Asn62 by two hydrogen bonds in the wild-type protein, and in Asp66His, the biggest change observed is a tremendous energy increase caused by hydrogen bond breakage to Asn62. Shifts in the side chain and new hydrogen bond formation are observed for Lys54 compared to the wild-type protein (Asn54) and result in closer contact to Val84. Asp50Asn causes a significant decrease in bond energy, and residual charge reversal repels the ion and metabolites and, hence, inhibits their transportation. Such perturbations are likely to be a factor contributing to abnormal functioning of ion channels, resulting cell death and disease.

De-novo Hybrid Protein Design for Biodegradation of Organophosphate Pesticides

  • Awasthi, Garima;Yadav, Ruchi;Srivastava, Prachi
    • 한국미생물·생명공학회지
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    • 제47권2호
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    • pp.278-288
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    • 2019
  • In the present investigation, we attempted to design a protocol to develop a hybrid protein with better bioremediation capacity. Using in silico approaches, a Hybrid Open Reading Frame (Hybrid ORF) is developed targeting the genes of microorganisms known for degradation of organophosphates. Out of 21 genes identified through BLAST search, 8 structurally similar genes (opdA, opd, opaA, pte RO, pdeA, parC, mpd and phnE) involved in biodegradation were screened. Gene conservational analysis categorizes these organophosphates degrading 8 genes into 4 super families i.e., Metallo-dependent hydrolases, Lactamase B, MPP and TM_PBP2 superfamily. Hybrid protein structure was modeled using multi-template homology modeling (3S07_A; 99%, 1P9E_A; 98%, 2ZO9_B; 33%, 2DXL_A; 33%) by $Schr{\ddot{o}}dinger$ software suit version 10.4.018. Structural verification of protein models was done using Ramachandran plot, it was showing 96.0% residue in the favored region, which was verified using RAMPAGE. The phosphotriesterase protein was showing the highest structural similarity with hybrid protein having raw score 984. The 5 binding sites of hybrid protein were identified through binding site prediction. The docking study shows that hybrid protein potentially interacts with 10 different organophosphates. The study results indicate that the hybrid protein designed has the capability of degrading a wide range of organophosphate compounds.

Targeted Base Editing via RNA-Guided Cytidine Deaminases in Xenopus laevis Embryos

  • Park, Dong-Seok;Yoon, Mijung;Kweon, Jiyeon;Jang, An-Hee;Kim, Yongsub;Choi, Sun-Cheol
    • Molecules and Cells
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    • 제40권11호
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    • pp.823-827
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    • 2017
  • Genome editing using programmable nucleases such as CRISPR/Cas9 or Cpf1 has emerged as powerful tools for gene knock-out or knock-in in various organisms. While most genetic diseases are caused by point mutations, these genome-editing approaches are inefficient in inducing single-nucleotide substitutions. Recently, Cas9-linked cytidine deaminases, named base editors (BEs), have been shown to convert cytidine to uridine efficiently, leading to targeted single-base pair substitutions in human cells and organisms. Here, we first report on the generation of Xenopus laevis mutants with targeted single-base pair substitutions using this RNA-guided programmable deaminase. Injection of base editor 3 (BE3) ribonucleoprotein targeting the tyrosinase (tyr) gene in early embryos can induce site-specific base conversions with the rates of up to 20.5%, resulting in oculocutaneous albinism phenotypes without off-target mutations. We further test this base-editing system by targeting the tp53 gene with the result that the expected single-base pair substitutions are observed at the target site. Collectively, these data establish that the programmable deaminases are efficient tools for creating targeted point mutations for human disease modeling in Xenopus.

레서핀 반복 투여를 통한 제브라피쉬 우울증 모델 (Chronic Reserpine Administration for Depression Modeling in Zebrafish)

  • 김세영;한창수;고영훈;김용구;윤호경;이종하;김수현;이찬희;신철민
    • 생물정신의학
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    • 제30권1호
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    • pp.17-23
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    • 2023
  • Objectives This study aims to develop valid experimental models for depression through chronic reserpine exposure to zebrafish (Danio rerio). Methods The effect of chronic reserpine on zebrafish behavior in the novel tank was examined. Changes of gene expression on telencephalon were also investigated. Results Chronic reserpine (40 mg/L, 7 days) induced overt behavioral effects, but markedly reduced activity, resembling motor retardation in depression. In telencephalon of zebrafish, gene expression associated with monoamine oxidase and norepinephrine transporter was decreased. Expression of serotonin transporter gene was increased. Conclusions Our results show that the pharmacological model of depression in zebrafish can induce not only behavioral changes, but also monoamine changes in the homology of human mood regulation centers.

Application of data fusion modeling for the prediction of auxin response elements in Zea mays for food security purposes

  • Nesrine Sghaier;Rayda Ben Ayed;Ahmed Rebai
    • Genomics & Informatics
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    • 제20권4호
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    • pp.45.1-45.7
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    • 2022
  • Food security will be affected by climate change worldwide, particularly in the developing world, where the most important food products originate from plants. Plants are often exposed to environmental stresses that may affect their growth, development, yield, and food quality. Auxin is a hormone that plays a critical role in improving plants' tolerance of environmental conditions. Auxin controls the expression of many stress-responsive genes in plants by interacting with specific cis-regulatory elements called auxin-responsive elements (AuxREs). In this work, we performed an in silico prediction of AuxREs in promoters of five auxin-responsive genes in Zea mays. We applied a data fusion approach based on the combined use of Dempster-Shafer evidence theory and fuzzy sets. Auxin has a direct impact on cell membrane proteins. The short-term auxin response may be represented by the regulation of transmembrane gene expression. The detection of an AuxRE in the promoter of prolyl oligopeptidase (POP) in Z. mays and the 3-fold overexpression of this gene under auxin treatment for 30 min indicated the role of POP in maize auxin response. POP is regulated by auxin to perform stress adaptation. In addition, the detection of two AuxRE TGTCTC motifs in the upstream sequence of the bx1 gene suggests that bx1 can be regulated by auxin. Auxin may also be involved in the regulation of dehydration-responsive element-binding and some members of the protein kinase superfamily.

EFFECT OF NEGATIVE FEEDBACK LOOP WITH NRF1 AND MIR-378 OF NONALCOHOLIC FATTY LIVER DISEASE: A MATHEMATICAL MODELING APPROACH

  • Lee, SiEun;Shin, Kiyeon
    • East Asian mathematical journal
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    • 제36권3호
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    • pp.365-376
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    • 2020
  • Nonalcoholic fatty liver is a type of fatty liver in which fat accumulates in the liver without alcohol. In the accumulation, Nrf1 and miR-378 genes play very important role, so called negative feedback loop, in which the two genes suppress the other's production. In other words, Nrf1 activates fatty acid oxidation which promotes fat consumption in the liver, while miR-378 deactivates fatty acid oxidation. Thus, both genes regulate nonalcoholic fatty liver. In this paper, the negative feedback loop of Nrf1 and miR-378 are expressed by a system of ordinary differential equations. And, bifurcation simulation shows the change in the amount of each gene with significant parameter range changes. Bifurcation simulation has also used to determine the thresholds for transit between disease and steady state.

Empirical modeling of flexural and splitting tensile strengths of concrete containing fly ash by GEP

  • Saridemir, Mustafa
    • Computers and Concrete
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    • 제17권4호
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    • pp.489-498
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    • 2016
  • In this paper, the flexural strength ($f_{fs}$) and splitting tensile strength ($f_{sts}$) of concrete containing different proportions of fly ash have been modeled by using gene expression programming (GEP). Two GEP models called GEP-I and GEP-II are constituted to predict the $f_{fs}$ and $f_{sts}$ values, respectively. In these models, the age of specimen, cement, water, sand, aggregate, superplasticizer and fly ash are used as independent input parameters. GEP-I model is constructed by 292 experimental data and trisected into 170, 86 and 36 data for training, testing and validating sets, respectively. Similarly, GEP-II model is constructed by 278 experimental data and trisected into 142, 70 and 66 data for training, testing and validating sets, respectively. The experimental data used in the validating set of these models are independent from the training and testing sets. The results of the statistical parameters obtained from the models indicate that the proposed empirical models have good prediction and generalization capability.

Reliability-based modeling of punching shear capacity of FRP-reinforced two-way slabs

  • Kurtoglu, Ahmet Emin;Cevik, Abdulkadir;Albegmprli, Hasan M.;Gulsan, Mehmet Eren;Bilgehan, Mahmut
    • Computers and Concrete
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    • 제17권1호
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    • pp.87-106
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    • 2016
  • This paper deals with the reliability analysis of design formulations derived for predicting the punching shear capacity of FRP-reinforced two-way slabs. Firstly, a new design code formulation was derived by means of gene expression programming. This formulation differs from the existing ones as the slab length (L) was introduced in the equation. Next, the proposed formulation was tested for its generalization capability by a parametric study. Then, the stochastic analyses of derived and existing formulations were performed by Monte Carlo simulation. Finally, the reliability analyses of these equations were carried out based on the results of stochastic analysis and the ultimate state function of ASCE-7 and ACI-318 (2011). The results indicate that the prediction performance of new formulation is significantly higher as compared to available design equations and its reliability index is within acceptable limits.

Developing JSequitur to Study the Hierarchical Structure of Biological Sequences in a Grammatical Inference Framework of String Compression Algorithms

  • Galbadrakh, Bulgan;Lee, Kyung-Eun;Park, Hyun-Seok
    • Genomics & Informatics
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    • 제10권4호
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    • pp.266-270
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    • 2012
  • Grammatical inference methods are expected to find grammatical structures hidden in biological sequences. One hopes that studies of grammar serve as an appropriate tool for theory formation. Thus, we have developed JSequitur for automatically generating the grammatical structure of biological sequences in an inference framework of string compression algorithms. Our original motivation was to find any grammatical traits of several cancer genes that can be detected by string compression algorithms. Through this research, we could not find any meaningful unique traits of the cancer genes yet, but we could observe some interesting traits in regards to the relationship among gene length, similarity of sequences, the patterns of the generated grammar, and compression rate.

발생모델의 진화를 위한 DNA 코딩방법 (DNA Coding Method for Evolution of Developmental Model)

  • 심귀보;이동욱
    • 대한전자공학회:학술대회논문집
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    • 대한전자공학회 1999년도 하계종합학술대회 논문집
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    • pp.464-467
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    • 1999
  • Rapid progress in the modeling of biological structures and simulation of their development has occurred over the last few years. Cellular automata (CA) and Lindenmayer-system(L-system) are the representative models of development/morphogenesis of multicellular organism. L-system is applied to the visualization of biological plant. Also, CA are applied to the study of artificial life and to the construction of an artificial brain. To design the L-system and CA automatically, we make this model evolve. It is necessary to code the developmental rules for evolution. In this paper, we propose a DNA coding method for evolution the models of development/morphogenesis of biological multicellular organisms. DNA coding has the redundancy and overlapping of gene and is apt for the representation of the rule. In this paper, we propose the DNA coding method of CA and L-system.

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