担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）

DOI： 10.1186/s12859-022-05009-x

DOI： 10.1186/s12859-022-05009-x

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）

DOI： 10.3389/fphar.2022.995597

担当区分：筆頭著者,　責任著者   記述言語：日本語   掲載種別：研究論文（研究会，シンポジウム資料等）

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）

DOI： 10.2197/ipsjtbio.14.30

記述言語：英語   掲載種別：研究論文（学術雑誌）

© 2019, The Author(s). The complex ammonium transport and assimilation network of E. coli involves the ammonium transporter AmtB, the regulatory proteins GlnK and GlnB, and the central N-assimilating enzymes together with their highly complex interactions. The engineering and modelling of such a complex network seem impossible because functioning depends critically on a gamut of data known at patchy accuracy. We developed a way out of this predicament, which employs: (i) a constrained optimization-based technology for the simultaneous fitting of models to heterogeneous experimental data sets gathered through diverse experimental set-ups, (ii) a ‘rubber band method’ to deal with different degrees of uncertainty, both in experimentally determined or estimated parameter values and in measured transient or steady-state variables (training data sets), (iii) integration of human expertise to decide on accuracies of both parameters and variables, (iv) massive computation employing a fast algorithm and a supercomputer, (v) an objective way of quantifying the plausibility of models, which makes it possible to decide which model is the best and how much better that model is than the others. We applied the new technology to the ammonium transport and assimilation network, integrating recent and older data of various accuracies, from different expert laboratories. The kinetic model objectively ranked best, has E. coli's AmtB as an active transporter of ammonia to be assimilated with GlnK minimizing the futile cycling that is an inevitable consequence of intracellular ammonium accumulation. It is 130 times better than a model with facilitated passive transport of ammonia.

DOI： 10.1038/s41540-019-0091-6

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担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（研究会，シンポジウム資料等）

担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（研究会，シンポジウム資料等）

記述言語：英語   掲載種別：研究論文（学術雑誌）

© 2017 Elsevier Ltd Oscillatory phenomena play a major role in organisms. In some biological oscillations such as cell cycles and heartbeats, the period can be tuned without significant changes in the amplitude. This property is called (period) tunability, one of the prominent features of biological oscillations. However, how biological oscillators produce tunable oscillations remains largely unexplored. We tackle this question using computational experiments. It has been reported that positive-plus-negative feedback oscillators produce tunable oscillations through the hysteresis-based mechanism. First, in this study, we confirmed that positive-plus-negative feedback oscillators generate tunable oscillations. Second, we found that tunability is positively correlated with the dynamic range of oscillations. Third, we showed that long negative feedback oscillators without any additional positive feedback loops can produce tunable oscillations. Finally, we computationally demonstrated that by lengthening the negative feedback loop, the Repressilator, known as a non-tunable synthetic gene oscillator, can be converted into a tunable oscillator. This work provides synthetic biologists with clues to design tunable gene oscillators.

DOI： 10.1016/j.jtbi.2017.12.014

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）

<p>Kinetic modeling is a powerful tool to understand how a biochemical system behaves as a whole. To develop a realistic and predictive model, kinetic parameters need to be estimated so that a model fits experimental data. However, parameter estimation remains a major bottleneck in kinetic modeling. To accelerate parameter estimation, we developed a C library for real-coded genetic algorithms (libRCGA). In libRCGA, two real-coded genetic algorithms (RCGAs), viz. the Unimodal Normal Distribution Crossover with Minimal Generation Gap (UNDX/MGG) and the Real-coded Ensemble Crossover star with Just Generation Gap (REX^star/JGG), are implemented in C language and paralleled by Message Passing Interface (MPI). We designed libRCGA to take advantage of high-performance computing environments and thus to significantly accelerate parameter estimation. Constrained optimization formulation is useful to construct a realistic kinetic model that satisfies several biological constraints. libRCGA employs stochastic ranking to efficiently solve constrained optimization problems. In the present paper, we demonstrate the performance of libRCGA through benchmark problems and in realistic parameter estimation problems. libRCGA is freely available for academic usage at http://kurata21.bio.kyutech.ac.jp/maeda/index.html.</p>

DOI： 10.2197/ipsjtbio.11.31

CiNii Article

その他リンク： https://ci.nii.ac.jp/naid/130007483197

記述言語：英語   掲載種別：研究論文（学術雑誌）

© 2015 The Society for Biotechnology, Japan. Computational analysis of metabolic fluxes is essential in understanding the structure and function of a metabolic network and in rationally designing genetically modified mutants for an engineering purpose. We had presented the genetic modification flux (GMF) that predicts the flux distribution of a broad range of genetically modified mutants. To enhance the feasibility and usability of GMF, we have developed a web application with a metabolic network database to predict a flux distribution of genetically modified mutants. One hundred and twelve data sets of Escherichia coli, Corynebacterium glutamicum, Saccharomyces cerevisiae, and Chinese hamster ovary were registered as standard models.

DOI： 10.1016/j.jbiosc.2015.12.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）

© 2016 The Author(s). Background: A kinetic model provides insights into the dynamic response of biological systems and predicts how their complex metabolic and gene regulatory networks generate particular functions. Of many biological systems, Escherichia coli metabolic pathways have been modeled extensively at the enzymatic and genetic levels, but existing models cannot accurately reproduce experimental behaviors in a batch culture, due to the inadequate estimation of a specific cell growth rate and a large number of unmeasured parameters. Results: In this study, we developed a detailed kinetic model for the central carbon metabolism of E. coli in a batch culture, which includes the glycolytic pathway, tricarboxylic acid cycle, pentose phosphate pathway, Entner-Doudoroff pathway, anaplerotic pathway, glyoxylate shunt, oxidative phosphorylation, phosphotransferase system (Pts), non-Pts and metabolic gene regulations by four protein transcription factors: cAMP receptor, catabolite repressor/activator, pyruvate dehydrogenase complex repressor and isocitrate lyase regulator. The kinetic parameters were estimated by a constrained optimization method on a supercomputer. The model estimated a specific growth rate based on reaction kinetics and accurately reproduced the dynamics of wild-type E. coli and multiple genetic mutants in a batch culture. Conclusions: This model overcame the intrinsic limitations of existing kinetic models in a batch culture, predicted the effects of multilayer regulations (allosteric effectors and gene expression) on central carbon metabolism and proposed rationally designed fast-growing cells based on understandings of molecular processes.

DOI： 10.1186/s12934-016-0511-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）

© 2014 Maeda et al. Background: One of the distinctive features of biological oscillators such as circadian clocks and cell cycles is robustness which is the ability to resume reliable operation in the face of different types of perturbations. In the previous study, we proposed multiparameter sensitivity (MPS) as an intelligible measure for robustness to fluctuations in kinetic parameters. Analytical solutions directly connect the mechanisms and kinetic parameters to dynamic properties such as period, amplitude and their associated MPSs. Although negative feedback loops are known as common structures to biological oscillators, the analytical solutions have not been presented for a general model of negative feedback oscillators. Results: We present the analytical expressions for the period, amplitude and their associated MPSs for a general model of negative feedback oscillators. The analytical solutions are validated by comparing them with numerical solutions. The analytical solutions explicitly show how the dynamic properties depend on the kinetic parameters. The ratio of a threshold to the amplitude has a strong impact on the period MPS. As the ratio approaches to one, the MPS increases, indicating that the period becomes more sensitive to changes in kinetic parameters. We present the first mathematical proof that the distributed time-delay mechanism contributes to making the oscillation period robust to parameter fluctuations. The MPS decreases with an increase in the feedback loop length (i.e., the number of molecular species constituting the feedback loop). Conclusions: Since a general model of negative feedback oscillators was employed, the results shown in this paper are expected to be true for many of biological oscillators. This study strongly supports that the hypothesis that phosphorylations of clock proteins contribute to the robustness of circadian rhythms. The analytical solutions give synthetic biologists some clues to design gene oscillators with robust and desired period.

DOI： 10.1186/1752-0509-8-S5-S1

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記述言語：英語   掲載種別：研究論文（学術雑誌）

In systems biology, computer simulation of the biochemical networks of a microbial cell is a powerful method to predict their function and phenotype under different culture conditions and genetic modifications. Construction of a virtual microbe, a generic mathematical model of cell growth and metabolism, can be an ambitious but realistic project. It would enable the rational design of a biochemical network to enhance the production of useful metabolites and proteins. However, there exist critical problems, such as parameter uncertainty, mechanism complexity and high dimensionality of the model. We would like to review the dynamic models of the biochemical networks with their problems, providing insight into developing a virtual microbe. © 2014 The Society of Chemical Engineers, Japan.

DOI： 10.1252/jcej.13we152

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記述言語：英語   掲載種別：研究論文（学術雑誌）

Mathematical modeling has become a standard technique to understand the dynamics of complex biochemical systems. To promote the modeling, we had developed the CADLIVE dynamic simulator that automatically converted a biochemical map into its associated mathematical model, simulated its dynamic behaviors and analyzed its robustness. To enhance the feasibility by CADLIVE and extend its functions, we propose the CADLIVE toolbox available for MATLAB, which implements not only the existing functions of the CADLIVE dynamic simulator, but also the latest tools including global parameter search methods with robustness analysis. The seamless, bottom-up processes consisting of biochemical network construction, automatic construction of its dynamic model, simulation, optimization, and S-system analysis greatly facilitate dynamic modeling, contributing to the research of systems biology and synthetic biology. This application can be freely downloaded from http://www.cadlive.jp/CADLIVE- MATLAB/ together with an instruction. © 2014 Springer-Verlag.

DOI： 10.1007/s00449-014-1167-8

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記述言語：日本語   掲載種別：研究論文（学術雑誌）

アンモニアは大腸菌にとって最適な窒素源である．大腸菌は，TCA 回路の中間代謝物である α-ケトグルタル酸にアンモニアを付加し，グルタミン酸とグルタミンを合成する．細胞内の窒素のほとんどはこの ２ つの代謝物に由来するものである．このような理由から，大腸菌がどのようにアンモニアを同化し，グルタミン酸とグルタミンの合成を制御しているのか明らかにすることは重要である．我々は，大腸菌アンモニア同化システムの新しいダイナミックモデルを構築した．動力学パラメータ推定では，推定値と測定値の差が最小になるように遺伝的アルゴリズムにペナルティ戦略を組み合わせた．我々のモデルは，近年発表されたメタボロームデータを定量的に再現できる．最近，グルタミン酸合成酵素に対するアスパラギン酸の競争阻害の重要性が指摘されたが，本稿ではその検証も行う．また GOGAT 欠損株と GOGAT 欠損サプレッサー変異株の解析も行う．アンモニアが豊富な条件では，グルタミン酸の過剰な蓄積によってサプレッサー変異株は野生株よりも増殖が遅いことが予測された．

CiNii Article

その他リンク： https://ci.nii.ac.jp/naid/110009605329

記述言語：英語   掲載種別：研究論文（学術雑誌）

Computer simulation is an important technique to capture the dynamics of biochemical networks. Since few quantitative values are measured in vivo, the values for unmeasured parameters should be estimated so that the simulation agrees with the experimental data. Considering the sparsity and error rates of experimentally measured data, the first thing is not to find a numerically exact and global solution but to explore a variety of the plausible parameter solutions. To find many plausible parameter solutions without any biases, we developed the two-phase search (TPS) method. However, calculation complexity makes it hard for TPS to optimize a large-scale dynamic model. In this study divide-and-conquer methods are used to solve this problem. The flux module decomposition (FMD) is first proposed that separates a complex, large-scale dynamic model into multiple flux modules without deteriorating its basic control architectures. FMD is combined with TPS, named FMD-TPS, to find many plausible parameter solutions for a dynamic model. To demonstrate the feasibility of FMD-TPS, it is applied to the E. coli ammonia assimilation system that consists of multiple-feedback loops. The variability of the solutions is verified by measuring the space distribution of the parameter solution vectors and by defining the binary vectors checking the consistency with biological behaviors. Compared with non-decomposition methods, FMD-TPS efficiently explored a variety of plausible parameter solutions that reproduce the dynamic behaviors in vivo. © 2012 Springer-Verlag.

DOI： 10.1007/s00449-012-0789-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）

© The Author 2013. In synthetic biology and systems biology, a bottom-up approach can be used to construct a complex, modular, hierarchical structure of biological networks. To analyze or design such networks, it is critical to understand the relationship between network structure and function, the mechanism through which biological parts or biomolecules are assembled into building blocks or functional networks. A functional network is defined as a subnetwork of biomolecules that performs a particular function.Understanding the mechanism of building functional networks would help develop a methodology for analyzing the structure of large-scale networks and design a robust biological circuit to perform a target function.We propose a biological functional network database, named BioFNet, which can cover the whole cell at the level of molecular interactions. The BioFNet takes an advantage in implementing the simulation program for the mathematical models of the functional networks, visualizing the simulated results. It presents a sound basis for rational design of biochemical networks and for understanding how functional networks are assembled to create complex high-level functions, which would reveal design principles underlying molecular architectures.

DOI： 10.1093/bib/bbt048

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記述言語：英語   掲載種別：研究論文（学術雑誌）

Computer simulation has been an important technique to capture the dynamics of biochemical networks. In most networks, however, few kinetic parameters have been measured in vivo because of experimental complexity. We develop a kinetic parameter estimation system, named the CADLIVE Optimizer, which comprises genetic algorithms-based solvers with a graphical user interface. This optimizer is integrated into the CADLIVE Dynamic Simulator to attain efficient simulation for dynamic models. © 2012 Inoue et al.; licensee BioMed Central Ltd.

DOI： 10.1186/1751-0473-7-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）

Many organisms have evolved molecular clocks to anticipate daily changes in their environment. The molecular mechanisms by which the circadian clock network produces sustained cycles have extensively been studied and transcriptional-translational feedback loops are common structures to many organisms. Although a simple or single feedback loop is sufficient for sustained oscillations, circadian clocks implement multiple, complicated feedback loops. In general, different types of feedback loops are suggested to affect the robustness and entrainment of circadian rhythms. To reveal the mechanism by which such a complex feedback system evolves, we quantify the robustness and light entrainment of four competing models: the single, semi-dual, dual, and redundant feedback models. To extract the global properties of those models, all plausible kinetic parameter sets that generate circadian oscillations are searched to characterize their oscillatory features. To efficiently perform such analyses, we used the two-phase search (TPS) method as a fast and non-biased search method and quasi-multiparameter sensitivity (QMPS) as a fast and exact measure of robustness to uncertainty of all kinetic parameters. So far the redundant feedback model has been regarded as the most robust oscillator, but our extensive analysis corrects or overcomes this hypothesis. The dual feedback model, which is employed in biology, provides the most robust oscillator to multiple parameter perturbations within a cell and most readily entrains to a wide range of light-dark cycles. The kinetic symmetry between the dual loops and their coupling via a protein complex are found critically responsible for robust and entrainable oscillations. We first demonstrate how the dual feedback architecture with kinetic symmetry evolves out of many competing feedback systems. © 2012 Maeda, Kurata.

DOI： 10.1371/journal.pone.0030489

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記述言語：英語   掲載種別：研究論文（学術雑誌）

To synthesize natural or artificial life, it is critically important to understand the design principles of how biochemical networks generate particular cellular functions and evolve complex systems in comparison with engineering systems. Cellular systems maintain their robustness in the face of perturbations arising from environmental and genetic variations. By analogy to control engineering architectures, the complexity of modular structures within a cell can be attributed to the necessity of achieving robustness. To reveal such a biological design, the E. coli ammonia assimilation system is analyzed, which consists of complex but highly structured modules: the glutamine synthetase (GS) activity feedback control module with bifunctional enzyme cascades for catalyzing reversible reactions, and the GS synthesis feedback control module with positive and negative feedback loops. We develop a full-scale dynamic model that unifies the two modules, and we analyze its robustness and fine tuning with respect to internal and external perturbations. The GS activity control is added to the GS synthesis module to improve its transient response to ammonia depletion, compensating for the tradeoffs of each module, but its robustness to internal perturbations is lost. These findings suggest some design principles necessary for the synthesis of life. © 2011 Massachusetts Institute of Technology.

DOI： 10.1162/artl_a_00049

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記述言語：英語   掲載種別：研究論文（学術雑誌）

Computer simulation is an important technique to capture the dynamics of biochemical networks. Numerical optimization is the key to estimate the values of kinetic parameters so that the dynamic model reproduces the behaviors of the existing experimental data. It is required to develop general strategies for the optimization of complex biochemical networks with a huge space of search parameters, under the condition that kinetic and quantitative data are hardly available. We propose an integrative and practical strategy for optimizing a complex dynamic model by using qualitative and incomplete experimental data. The key technologies are the divide and conquer method for reducing the search space, handling of multiple objective functions representing different types of biological behaviors, and design of rule-based objective functions that are suitable for qualitative and error-prone experimental data. This strategy is applied to optimizing a dynamic model of the yeast cell cycle to demonstrate the feasibility of it. © 2010 Springer-Verlag.

DOI： 10.1007/s00449-010-0486-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）

Robustness is the ability to resume reliable operation in the face of different types of perturbations. Analysis of how network structure achieves robustness enables one to understand and design cellular systems. It is typically true that all parameters simultaneously differ from their nominal values in vivo, but there have been few intelligible measures to estimate the robustness of a system's function to the uncertainty of all parameters. We propose a numerical and fast measure of a robust property to the uncertainty of all kinetic parameters, named quasi-multiparameter sensitivity (QMPS), which is defined as the sum of the squared magnitudes of single-parameter sensitivities. Despite its plain idea, it has hardly been employed in analysis of biological models. While QMPS is theoretically derived as a linear model, QMPS can be consistent with the expected variance simulated by the widely used Monte Carlo method in nonlinear biological models, when relatively small perturbations are given. To demonstrate the feasibility of QMPS, it is employed for numerical comparison to analyze the mechanism of how specific regulations generate robustness in typical biological models. QMPS characterizes the robustness much faster than the Monte Carlo method, thereby enabling the extensive search of a large parameter space to perform the numerical comparison between alternative or competing models. It provides a theoretical or quantitative insight to an understanding of how specific network structures are related to robustness. In circadian oscillators, a negative feedback loop with multiple phosphorylations is demonstrated to play a critical role in generating robust cycles to the uncertainty of multiple parameters. © 2010 Elsevier Ltd.

DOI： 10.1016/j.jtbi.2010.12.012

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記述言語：英語   掲載種別：研究論文（学術雑誌）

Dynamic simulations are essential for understanding the mechanism of how biochemical networks generate robust properties to environmental stresses or genetic changes. However, typical dynamic modeling and analysis yield only local properties regarding a particular choice of plausible values of kinetic parameters, because it is hard to measure the exact values in vivo. Global and firm analyses are needed that consider how the changes in parameter values affect the results. A typical solution is to systematically analyze the dynamic behaviors in large parameter space by searching all plausible parameter values without any biases. However, a random search needs an enormous number of trials to obtain such parameter values. Ordinary evolutionary searches swiftly obtain plausible parameters but the searches are biased. To overcome these problems, we propose the two-phase search method that consists of a random search and an evolutionary search to effectively explore all possible solution vectors of kinetic parameters satisfying the target dynamics. We demonstrate that the proposed method enables a nonbiased and high-speed parameter search for dynamic models of biochemical networks through its applications to several benchmark functions and to the E. coli heat shock response model. © 2009 Information Processing Society of Japan.

DOI： 10.2197/ipsjtbio.2.2

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記述言語：英語   掲載種別：研究論文（学術雑誌）

概日リズムは地球上の多くの生物が持つ約 24 時間周期の発振機構である．この発振機構の核はネガティブフィードバックループである．本来 1 つのネガティブフィードバックループで発振可能だが，ショウジョウバエの発振機構はインターロックされた 2 つのネガティブフィードバックループから成る．なぜこのような複雑な発振機構を採用しているのだろうか．本報告では，インターロックフィードバックがもたらす概日リズムのロバストネスとそのトレードオフの関係を数理モデルを用いて解明する．The circadian clock refers to the oscillator that most organisms on the earth have and its period is about 24 hours. Negative feedback loops play an important role in the oscillator. While only one negative feedback loop can produce an oscillating behavior, the circadian oscillator in Drosophila has two interlocked negative feedback loops. Why does Drosophila have such a complex mechanism? In this report, we elucidate the mechanism of how the Drosophila circadian rhythm generates robustness and trade-off by using mathematical models.

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記述言語：英語   掲載種別：研究論文（学術雑誌）

Numerical simulation of differential equation systems plays a major role in the understanding of how metabolic network models generate particular cellular functions. On the other hand, the classical and technical problems for stiff differential equations still remain to be solved, while many elegant algorithms have been presented. To relax the stiffness problem, we propose new practical methods: the gradual update of differential-algebraic equations based on gradual application of the steady-state approximation to stiff differential equations, and the gradual update of the initial values in differential-algebraic equations. These empirical methods show a high efficiency for simulating the steady-state solutions for the stiff differential equations that existing solvers alone cannot solve. They are effective in extending the applicability of dynamic simulation to biochemical network models. © 2008 Springer-Verlag.

DOI： 10.1007/s00449-008-0244-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）

Dynamic simulations are essential for understanding the mechanism of how biochemical networks generate robust properties to environmental stresses or genetic changes. However, typical dynamic modeling and analysis yield only local properties regarding a particular choice of plausible values of kinetic parameters, because it is hard to measure the exact values <i>in vivo</i>. Global and firm analyses are needed that consider how the changes in parameter values affect the results. A typical solution is to systematically analyze the dynamic behaviors in large parameter space by searching all plausible parameter values without any biases. However, a random search needs an enormous number of trials to obtain such parameter values. Ordinary evolutionary searches swiftly obtain plausible parameters but the searches are biased. To overcome these problems, we propose the two-phase search method that consists of a random search and an evolutionary search to effectively explore all possible solution vectors of kinetic parameters satisfying the target dynamics. We demonstrate that the proposed method enables a nonbiased and high-speed parameter search for dynamic models of biochemical networks through its applications to several benchmark functions and to the <i>E. coli</i> heat shock response model.

DOI： 10.11185/imt.4.377

CiNii Article

その他リンク： https://ci.nii.ac.jp/naid/130000120679

記述言語：日本語   掲載種別：研究論文（学術雑誌）

ダイナミックシミュレーションは環境ストレスや遺伝的変化に対してロバストネスを生み出す生化学ネットワークのメカニズムの解明に不可欠である。しかし、これまでに行われた多くのシミュレーションや解析は特定の速度パラメータ値に依存している。速度パラメータの正確な測定は困難であるので、特定のパラメータ値に依存するのではなく、パラメータ値の変化が与える影響を考慮した解析が必要である。これを可能にするためには細胞内の挙動を再現しうる全ての速度パラメータ値を広い探索空間から偏りなく探し出さなければならない。本稿では、ランダム探索と進化的探索を組み合わせた新しいパラメータ探索法、Two-phase search 法を提案する。そして、この手法が偏りなく効率的に速度パラメータを探索できることを示す。Dynamic simulations are essential for understanding the mechanism of how biochemical networks generate robust properties to environmental stresses or genetic changes. However, typical dynamic modeling and analysis yield only local properties regarding a particular choice of plausible values of kinetic parameters. Global and firm analyses are needed that consider how the changes in parameter values affect the results. A typical solution is to systematically analyze the dynamic behaviors in large parameter space by searching all plausible parameter values without any biases. In this paper, we propose the two-phase search method that consists of a random search and an evolutionary search to effectively explore all possible solution vectors of kinetic parameters satisfying the target dynamics. It enables a nonbiased and high-speed parameter search for dynamic models of biochemical networks.

CiNii Article

その他リンク： https://ci.nii.ac.jp/naid/110006967151

記述言語：英語   掲載種別：研究論文（学術雑誌）

Biochemical network maps are helpful for understanding the mechanism of how a collection of biochemical reactions generate particular functions within a cell. We developed a new and computationally feasible notation that enables drawing a wide resolution map from the domain-level reactions to phenomenological events and implemented it as the extended GUI network constructor of CADLIVE (Computer-Aided Design of LIVing systEms). The new notation presents 'Domain expansion' for proteins and RNAs, 'Virtual reaction and nodes' that are responsible for illustrating domain-based interaction and 'InnerLink' that links real complex nodes to virtual nodes to illustrate the exact components of the real complex. A modular box is also presented that packs related reactions as a module or a subnetwork, which gives CADLIVE a capability to draw biochemical maps in a hierarchical modular architecture. Furthermore, we developed a pathway search module for virtual knockout mutants as a built-in application of CADLIVE. This module analyzes gene function in the same way as molecular genetics, which simulates a change in mutant phenotypes or confirms the validity of the network map. The extended CADLIVE with the newly proposed notation is demonstrated to be feasible for computational simulation and analysis. © 2007 The Author(s).

DOI： 10.1093/nar/gkm769

Scopus

その他リンク： https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=36749043657&origin=inward

記述言語：英語   掲載種別：研究論文（学術雑誌）

ダイナミックシミュレーションはタンパク質や代謝物、遺伝子などから成る生命分子ネットワークの動的挙動を解析する手段である。生体内の動的挙動を再現するためには、リバースエンジニアリングの手法を用いて、多数の速度パラメータの値を決定する必要がある。我々はモジュール分割統合法と統計解析技術を組み合わせた最適化手法 DIS(Decomposition and lntegration with Statistical analysis)を開発した。これと遺伝的アルゴリズム（GA)を組み合わせることによって、通常のGAでは最適化困難な大規模生命分子ネットワークのパラメータ最適化に成功した。さらに、この最適化手法によってグローバルな最適解が得られた。Dynamic simulation is a way to analyze dynamics of biomolecular networks consisting of proteins, metabolites and genes. In order to simulate their intrinsic dynamics, it is necessary to optimize the values of many kinetic parameters by reverse-engineering. We developed a new optimization method, DIS (Decomposition and Integration with Statistical analysis) combining decomposition and integration method with statistical analysis. By using DIS and genetic algorithm (GA), we optimized the parameters of large-scale biomolecular network which conventional GA cannot optimize. In this article, we also show that this method can obtain global solutions.

CiNii Article

その他リンク： https://ci.nii.ac.jp/naid/110006403659

開催期間： 2019年11月01日   記述言語：英語  

開催期間： 2019年09月18日   記述言語：日本語  

開催期間： 2019年09月10日   記述言語：日本語  

開催期間： 2019年09月08日   記述言語：日本語  

開催期間： 2019年04月18日   記述言語：英語  

開催期間： 2019年04月02日 - 2019年04月03日   記述言語：英語  

開催期間： 2019年03月28日   記述言語：英語   開催地：University of Amsterdam  

開催期間： 2019年01月13日 - 2019年01月14日   記述言語：日本語  

開催期間： 2018年11月   記述言語：日本語  

開催期間： 2018年10月05日   記述言語：日本語  

開催期間： 2018年09月19日 - 2018年09月21日   記述言語：日本語  

開催期間： 2018年09月18日   記述言語：日本語  

受賞国：日本国