• Title/Summary/Keyword: Functional Prediction

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A Method for Protein Functional Flow Configuration and Validation (단백질 기능 흐름 모델 구성 및 평가 기법)

  • Jang, Woo-Hyuk;Jung, Suk-Hoon;Han, Dong-Soo
    • Journal of KIISE:Computing Practices and Letters
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    • v.15 no.4
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    • pp.284-288
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    • 2009
  • With explosively growing PPI databases, the computational approach for a prediction and configuration of PPI network has been a big stream in the bioinformatics area. Recent researches gradually consider physicochemical properties of proteins and support high resolution results with integration of experimental results. With regard to current research trend, it is very close future to complete a PPI network configuration of each organism. However, direct applying the PPI network to real field is complicated problem because PPI network is only a set of co-expressive proteins or gene products, and its network link means simple physical binding rather than in-depth knowledge of biological process. In this paper, we suggest a protein functional flow model which is a directed network based on a protein functions' relation of signaling transduction pathway. The vertex of the suggested model is a molecular function annotated by gene ontology, and the relations among the vertex are considered as edges. Thus, it is easy to trace a specific function's transition, and it can be a constraint to extract a meaningful sub-path from whole PPI network. To evaluate the model, 11 functional flow models of Homo sapiens were built from KEGG, and Cronbach's alpha values were measured (alpha=0.67). Among 1023 functional flows, 765 functional flows showed 0.6 or higher alpha values.

Theoretical Investigations on Structure and Function of Human Homologue hABH4 of E.coli ALKB4

  • Shankaracharya, Shankaracharya;Das, Saibal;Prasad, Dinesh;Vidyarthi, Ambarish Sharan
    • Interdisciplinary Bio Central
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    • v.2 no.3
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    • pp.8.1-8.5
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    • 2010
  • Introduction: Recently identified human homologues of ALKB protein have shown the activity of DNA damaging drugs, used for cancer therapy. Bioinformatics study of hABH2 and hABH3 had led to the discovery of a novel DNA repair mechanism. Very little is known about structure and function of hABH4, one of the members of this superfamily. Therefore, in present study we are intended to predict its structure and function through various bioinformatics tools. Materials and Methods: Modeling was done with modeler 9v7 to predict the 3D structure of the hABH4 protein. This model was validated with the program Procheck using Ramachandran plot statistics and was submitted to PMDB with ID PM0076284. The 3d2GO server was used to predict the functions. Residues at protein ligand and protein RNA binding sites were predicted with 3dLigandSite and KYG programs respectively. Results and Discussion: 3-D model of hABH4, ALKBH4.B99990003.pdb was predicted and evaluated. Validation result showed that 96.4 % residues lies in favored and additional allowed region of Ramachandran plot. Ligand binding residues prediction showed four Ligand clusters, having 24 ligands in cluster 1. Importantly, conserved pattern of Glu196-X-Pro198- Xn-His254 in the functional domain was detected. DNA and RNA binding sites were also predicted in the model. Conclusion and Prospects: The predicted and validated model of human homologue hABH4 resulted from this study may unveil the mechanism of DNA damage repair in human and accelerate the research on designing of appropriate inhibitors aiding in chemotherapy and cancer related diseases.

Evaluation and Prediction of Post-Hepatectomy Liver Failure Using Imaging Techniques: Value of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging

  • Keitaro Sofue;Ryuji Shimada;Eisuke Ueshima;Shohei Komatsu;Takeru Yamaguchi;Shinji Yabe;Yoshiko Ueno;Masatoshi Hori;Takamichi Murakami
    • Korean Journal of Radiology
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    • v.25 no.1
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    • pp.24-32
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    • 2024
  • Despite improvements in operative techniques and perioperative care, post-hepatectomy liver failure (PHLF) remains the most serious cause of morbidity and mortality after surgery, and several risk factors have been identified to predict PHLF. Although volumetric assessment using imaging contributes to surgical simulation by estimating the function of future liver remnants in predicting PHLF, liver function is assumed to be homogeneous throughout the liver. The combination of volumetric and functional analyses may be more useful for an accurate evaluation of liver function and prediction of PHLF than only volumetric analysis. Gadoxetic acid is a hepatocyte-specific magnetic resonance (MR) contrast agent that is taken up by hepatocytes via the OATP1 transporter after intravenous administration. Gadoxetic acid-enhanced MR imaging (MRI) offers information regarding both global and regional functions, leading to a more precise evaluation even in cases with heterogeneous liver function. Various indices, including signal intensity-based methods and MR relaxometry, have been proposed for the estimation of liver function and prediction of PHLF using gadoxetic acid-enhanced MRI. Recent developments in MR techniques, including high-resolution hepatobiliary phase images using deep learning image reconstruction and whole-liver T1 map acquisition, have enabled a more detailed and accurate estimation of liver function in gadoxetic acid-enhanced MRI.

Prediction of Treatment Outcome of Chemotherapy Using Perfusion Computed Tomography in Patients with Unresectable Advanced Gastric Cancer

  • Dong Ho Lee;Se Hyung Kim;Sang Min Lee;Joon Koo Han
    • Korean Journal of Radiology
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    • v.20 no.4
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    • pp.589-598
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    • 2019
  • Objective: To evaluate whether data acquired from perfusion computed tomography (PCT) parameters can aid in the prediction of treatment outcome after palliative chemotherapy in patients with unresectable advanced gastric cancer (AGC). Materials and Methods: Twenty-one patients with unresectable AGCs, who underwent both PCT and palliative chemotherapy, were prospectively included. Treatment response was assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 (i.e., patients who achieved complete or partial response were classified as responders). The relationship between tumor response and PCT parameters was evaluated using the Mann-Whitney test and receiver operating characteristic analysis. One-year survival was estimated using the Kaplan-Meier method. Results: After chemotherapy, six patients exhibited partial response and were allocated to the responder group while the remaining 15 patients were allocated to the non-responder group. Permeability surface (PS) value was shown to be significantly different between the responder and non-responder groups (51.0 mL/100 g/min vs. 23.4 mL/100 g/min, respectively; p = 0.002), whereas other PCT parameters did not demonstrate a significant difference. The area under the curve for prediction in responders was 0.911 (p = 0.004) for PS value, with a sensitivity of 100% (6/6) and specificity of 80% (12/15) at a cut-off value of 29.7 mL/100 g/min. One-year survival in nine patients with PS value > 29.7 mL/100 g/min was 66.7%, which was significantly higher than that in the 12 patients (33.3%) with PS value ≤ 29.7 mL/100 g/min (p = 0.019). Conclusion: Perfusion parameter data acquired from PCT demonstrated predictive value for treatment outcome after palliative chemotherapy, reflected by the significantly higher PS value in the responder group compared with the non-responder group.

Functional analysis of SH3 domain containing ring finger 2 during the myogenic differentiation of quail myoblast cells

  • Kim, Si Won;Lee, Jeong Hyo;Park, Tae Sub
    • Asian-Australasian Journal of Animal Sciences
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    • v.30 no.8
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    • pp.1183-1189
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    • 2017
  • Objective: Owing to the public availability of complete genome sequences, including avian species, massive bioinformatics analyses may be conducted for computational gene prediction and the identification of gene regulatory networks through various informatics tools. However, to evaluate the biofunctional activity of a predicted target gene, in vivo and in vitro functional genomic analyses should be a prerequisite. Methods: Due to a lack of quail genomic sequence information, we first identified the partial genomic structure and sequences of the quail SH3 domain containing ring finger 2 (SH3RF2) gene. Subsequently, SH3RF2 was knocked out using clustered regularly interspaced short palindromic repeat/Cas9 technology and single cell-derived SH3RF2 mutant sublines were established to study the biofunctional activity of SH3RF2 in quail myoblast (QM7) cells during muscle differentiation. Results: Through a T7 endonuclease I assay and genotyping analysis, we established an SH3RF2 knockout (KO) QM7#4 subline with 61 and 155 nucleotide deletion mutations in SH3RF2. After the induction of myotube differentiation, the expression profiles were analyzed and compared between regular QM7 and SH3RF2 KO QM7#4 cells by global RNA sequencing and bioinformatics analysis. Conclusion: We did not detect any statistically significant role of SH3RF2 during myotube differentiation in QM7 myoblast cells. However, additional experiments are necessary to examine the biofunctional activity of SH3RF2 in cell proliferation and muscle growth.

Evaluation of Environmental Factors to Determine the Distribution of Functional Feeding Groups of Benthic Macroinvertebrates Using an Artificial Neural Network

  • Park, Young-Seuk;Lek, Sovan;Chon, Tae-Soo;Verdonschot, Piet F.M.
    • Journal of Ecology and Environment
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    • v.31 no.3
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    • pp.233-241
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    • 2008
  • Functional feeding groups (FFGs) of benthic macroinvertebrates are guilds of invertebrate taxa that obtain food in similar ways, regardless of their taxonomic affinities. They can represent a heterogeneous assemblage of benthic fauna and may indicate disturbances of their habitats. The proportion of different groups can change in response to disturbances that affect the food base of the system, thereby offering a means of assessing disruption of ecosystem functioning. In this study, we used benthic macroinvertebrate communities collected at 650 sites of 23 different water types in the province of Overijssel, The Netherlands. Physical and chemical environmental factors were measured at each sampling site. Each taxon was assigned to its corresponding FFG based on its food resources. A multilayer perceptron (MLP) using a backpropagation algorithm, a supervised artificial neural network, was applied to evaluate the influence of environmental variables to the FFGs of benthic macroinvertebrates through a sensitivity analysis. In the evaluation of input variables, the sensitivity analysis with partial derivatives demonstrates the relative importance of influential environmental variables on the FFG, showing that different variables influence the FFG in various ways. Collector-filterers and shredders were mainly influenced by $Ca^{2+}$ and width of the streams, and scrapers were influenced mostly with $Ca^{2+}$ and depth, and predators were by depth and pH. $Ca^{2+}$ and depth displayed relatively high influence on all four FFGs, while some variables such as pH, %gravel, %silt, and %bank affected specific groups. This approach can help to characterize community structure and to ecologically assess target ecosystems.

Protein Function Finding Systems through Domain Analysis on Protein Hub Network (단백질 허브 네트워크에서 도메인분석을 통한 단백질 기능발견 시스템)

  • Kang, Tae-Ho;Ryu, Jea-Woon;Kim, Hak-Yong;Yoo, Jae-Soo
    • The Journal of the Korea Contents Association
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    • v.8 no.1
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    • pp.259-271
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    • 2008
  • We propose a protein function finding algorithm that is able to predict specific molecular function for unannotated proteins through domain analysis from protein-protein network. To do this, we first construct protein-protein interaction(PPI) network in Saccharomyces cerevisiae from MIPS databases. The PPI network(proteins; 3,637, interactions; 10,391) shows the characteristics of a scale-free network and a hierarchical network that proteins with a number of interactions occur in small and the inherent modularity of protein clusters. Protein-protein interaction databases obtained from a Y2H(Yeast Two Hybrid) screen or a composite data set include random false positives. To filter the database, we reconstruct the PPI networks based on the cellular localization. And then we analyze Hub proteins and the network structure in the reconstructed network and define structural modules from the network. We analyze protein domains from the structural modules and derive functional modules from them. From the derived functional modules with high certainty, we find tentative functions for unannotated proteins.

A Study on Dynamic Material Properties of Functional High Explosive Formulation Simulant Subjected to Dynamic Loading (동적하중을 받는 기능성 고폭화약조성 시뮬런트 재료물성 연구)

  • Park, Jungsu;Yeom, Kee Sun;Park, Chunghee;Jeong, Sehwan;Lee, Keundeuck;Huh, Hoon
    • Journal of the Korea Institute of Military Science and Technology
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    • v.16 no.6
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    • pp.857-866
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    • 2013
  • This paper is concerned with the material properties of functional high explosive(FHX) simulant at various strain rates ranging from $10^{-4}/sec$ to $10^1/sec$. Material properties of FHX at high strain rates are important in prediction of deformation modes of FHX in a warhead which undergoes dynamic loading. Inert FHX stimulant which has analogous mechanical properties with FHX was utilized for material tests due to safety issues. Uniaxial tensile tests at quasi-static strain rates ranging from $10^{-4}/sec$ to $10^{-2}/sec$ and intermediate strain rates ranging from $10^{-1}/sec$ to $10^1/sec$ were conducted with JANNAF specimen using a tensile testing machine, INTRON 5583, and developed high speed material testing machine, respectively. Uniaxial compressive tests at quasi-static strain rates and intermediate strain rates were conducted with cylindrical specimen using a dynamic materials testing machine, INSTRON 8801. And cyclic compressive loading tests were performed with various strain rates and strains. Deformation behaviors were investigated using captured images obtained from a high-speed camera.

Surface expression of TTYH2 is attenuated by direct interaction with β-COP

  • Ryu, Jiwon;Kim, Dong-Gyu;Lee, Young-Sun;Bae, Yeonju;Kim, Ajung;Park, Nammi;Hwang, Eun Mi;Park, Jae-Yong
    • BMB Reports
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    • v.52 no.7
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    • pp.445-450
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    • 2019
  • TTYH2 is a calcium-activated, inwardly rectifying anion channel that has been shown to be related to renal cancer and colon cancer. Based on the topological prediction, TTYH2 protein has five transmembrane domains with the extracellular N-terminus and the cytoplasmic C-terminus. In the present study, we identified a vesicle transport protein, ${\beta}$-COP, as a novel specific binding partner of TTYH2 by yeast two-hybrid screening using a human brain cDNA library with the C-terminal region of TTYH2 (TTYH2-C) as a bait. Using in vitro and in vivo binding assays, we confirmed the protein-protein interactions between TTYH2 and ${\beta}$-COP. We also found that the surface expression and activity of TTYH2 were decreased by co-expression with ${\beta}$-COP in the heterologous expression system. In addition, ${\beta}$-COP associated with TTYH2 in a native condition at a human colon cancer cell line, LoVo cells. The over-expression of ${\beta}$-COP in the LoVo cells led to a dramatic decrease in the surface expression and activity of endogenous TTYH2. Collectively, these data suggested that ${\beta}$-COP plays a critical role in the trafficking of the TTYH2 channel to the plasma membrane.

In silico approaches to discover the functional impact of non-synonymous single nucleotide polymorphisms in selective sweep regions of the Landrace genome

  • Shin, Donghyun;Won, Kyung-Hye;Song, Ki-Duk
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.12
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    • pp.1980-1990
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    • 2018
  • Objective: The aim of this study was to discover the functional impact of non-synonymous single nucleotide polymorphisms (nsSNPs) that were found in selective sweep regions of the Landrace genome Methods: Whole-genome re-sequencing data were obtained from 40 pigs, including 14 Landrace, 16 Yorkshire, and 10 wild boars, which were generated with the Illumina HiSeq 2000 platform. The nsSNPs in the selective sweep regions of the Landrace genome were identified, and the impacts of these variations on protein function were predicted to reveal their potential association with traits of the Landrace breed, such as reproductive capacity. Results: Total of 53,998 nsSNPs in the mapped regions of pigs were identified, and among them, 345 nsSNPs were found in the selective sweep regions of the Landrace genome which were reported previously. The genes featuring these nsSNPs fell into various functional categories, such as reproductive capacity or growth and development during the perinatal period. The impacts of amino acid sequence changes by nsSNPs on protein function were predicted using two in silico SNP prediction algorithms, i.e., sorting intolerant from tolerant and polymorphism phenotyping v2, to reveal their potential roles in biological processes that might be associated with the reproductive capacity of the Landrace breed. Conclusion: The findings elucidated the domestication history of the Landrace breed and illustrated how Landrace domestication led to patterns of genetic variation related to superior reproductive capacity. Our novel findings will help understand the process of Landrace domestication at the genome level and provide SNPs that are informative for breeding.