Yukako Tohsato | Ritsumeikan University (original) (raw)
Papers by Yukako Tohsato
Journal of Computational Biology, Feb 17, 2023
Genome-scale constraint-based metabolic networks play an important role in the simulation of grow... more Genome-scale constraint-based metabolic networks play an important role in the simulation of growth-coupled production, which means that cell growth and target metabolite production are simultaneously achieved. For growth-coupled production, a minimal reaction-network-based design is known to be effective. However, the obtained reaction networks often fail to be realized by gene deletions due to conflicts with gene-protein-reaction relations. Here, we developed gDel minRN that determines gene deletion strategies using mixed-integer linear programming to achieve growth-coupled production by repressing the maximum number of reactions via gene-protein-reaction relations. The results of computational experiments showed that gDel minRN could determine the core parts, which include only 30 to 55% of whole genes, for stoichiometrically feasible growth-coupled production for many target metabolites, which include useful vitamins such as biotin (vitamin B7), riboflavin (vitamin B2), and pantothenate (vitaminB5). Since gDel minRN calculates a constraint-based model of the minimum number of gene-associated reactions without conflict with gene-protein-reaction relations, it helps biological analysis of the core parts essential for growth-coupled production for each target metabolite. The source codes, implemented in MATLAB using CPLEX and COBRA Toolbox, are available on {{https://github.com/MetNetComp/gDel-minRN}}
Lecture Notes in Computer Science, 2022
PLOS ONE, Aug 12, 2020
BD5 is a new binary data format based on HDF5 (hierarchical data format version 5). It can be use... more BD5 is a new binary data format based on HDF5 (hierarchical data format version 5). It can be used for representing quantitative biological dynamics data obtained from bioimage informatics techniques and mechanobiological simulations. Biological Dynamics Markup Language (BDML) is an XML (Extensible Markup Language)-based open format that is also used to represent such data; however, it becomes difficult to access quantitative data in BDML files when the file size is large because parsing XML-based files requires large computational resources to first read the whole file sequentially into computer memory. BD5 enables fast random (i.e., direct) access to quantitative data on disk without parsing the entire file. Therefore, it allows practical reuse of data for understanding biological mechanisms underlying the dynamics.
Glycoconjugate Journal, Aug 14, 2012
Brine shrimp are primitive crustacean arthropodal model organisms, second to daphnia, which can s... more Brine shrimp are primitive crustacean arthropodal model organisms, second to daphnia, which can survive in high-salinity environments. Their oviposited cysts, cuticlecovered diapausing eggs, are highly resistant to dryness. To elucidate specialties of brine shrimp, this study characterized glycosphingolipids, which are signal transductionassociated material. A group of novel and complex fucosyl glycosphingolipids were separated and identified from cysts of the brine shrimp Artemia franciscana by repeated lipid extraction, alkaline methanolysis, acid treatment, successive column chromatography, and post-source decay measurements by matrix-assisted laser desorption/ionization time-offlight mass spectrometry. Structures of the glycosphingolipids were elucidated by conventional structural characterization and mass spectrometry, and the compounds were identified as GlcNAcβ1-3GalNAcβ1-4(GlcNAcα1-2Fucα1-3)GlcNAcβ1-3Manβ1-4Glcβ1-Cer, GalNAcβ1-4(Fucα1-3)GlcNAcβ 1-3GalNAcβ 1-4(GlcNAcα 1-2Fucα 1-3)GlcNAcβ1-3Manβ1-4Glcβ1-Cer, and GalNAcβ1-4 (GlcNAcα 1-2Fucα 1-3)GlcNAcβ 1-3GalNAcβ 1-4 (GlcNAcα1-2Fucα1-3)GlcNAcβ1-3Manβ1-4Glcβ1-Cer. These compounds also contained a branching, non-arthroseries disaccharide with an α-GlcNAc terminus, similar to that found in a previously reported ceramide hexasaccharide (III 3 (GlcNAcα2Fucα)-At 4 Cer). The glycans within these complex GSLs are longer than reported glycans of the animal kingdom containing α-GlcNAc terminus. These complex GSLs as well as the longest GSL with ten sugar residues, ceramide decasaccharide (CDeS), contain the fucosylated LacdiNAc sequence reported to associate with parasitism/ immunosuppression and the α-GlcNAc terminus reported to show a certain antibacterial effect in other reports. CDeS, the longest GSL of this species, was found in the highest amount, which indicates that CDeS may be functionally important. Keywords Sphingosine. Fucomannolipid. Terminal α-N-acetylglucosamine residue. Structure characterization. Branchiopoda. Dormant cyst Abbreviations CDeS Ceramide decasaccharide CHpS Ceramide heptasaccharide CHS Ceramide hexasaccharide CNS Ceramide nonasaccharide COS Ceramide octasaccharide GC Gas chromatography GSL Glycosphingolipid 1 H-NMR Proton nuclear magnetic resonance HPTLC High-performance thin-layer chromatography MALDI-TOF MS Matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry Electronic supplementary material The online version of this article
Lecture Notes in Computer Science, 2022
Ipsj Transactions on Bioinformatics, 2023
Identifying factors that contribute to microbial growth is important for realizing efficient prod... more Identifying factors that contribute to microbial growth is important for realizing efficient production of useful substrates. Our objective was to predict unknown metabolic pathways from experimental time-series data in model organisms such as Escherichia coli. We focused on a previous method that replaces the computation of auto-regression in the Granger causality test with non-parametric multiplicative regression (NPMR) to allow inferences on noisy and nonlinear data. We then proposed a new causal inference method that creates a multi-dimensional space based on the error between the time series predicted by NPMR and the original time series. We confirmed that the inference accuracy of the proposed method outperforms that of NPMR by 50% using short time series generated by coupled logistic equations, which allows for adjustment of the strength of the causal relationship. The proposed method was applied to simulation data obtained from a kinetic model for glycolysis in E. coli and achieved 61% accuracy.
The Japanese Biochemical Society/The Molecular Biology Society of Japan, Nov 2, 2015
Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme, 2001
Genome Informatics Series, 1999
The MINL problem is a problem that finds a minimum and reduced set of patterns explaining a given... more The MINL problem is a problem that finds a minimum and reduced set of patterns explaining a given set of positive example strings. By restricting the number of patterns to be a fixed constant in advance, a polynomial time algorithm that solves this problem is known [1]. This algorithm is applicable to determining gene clusters based on functional classification if genes having the same function are expressed with the same character. However, since gene function is typically classified hierarchically, the above algorithm can only be applied on a single level of the classification hierarchy. In this paper, we extend the MINL problem to cover hierarchical classifications, and propose a novel polynomial time algorithm utilizing entropy to solve the extended problem. The effectiveness of our method is demonstrated by applying the method to a gene cluster analysis on 9 complete genomes.
Motivation: The enzyme nomenclature system, commonly known as the enzyme commission (EC) number, ... more Motivation: The enzyme nomenclature system, commonly known as the enzyme commission (EC) number, plays a key role in classifying and predicting enzymatic reactions. However, numerous reactions have been described in various pathways that do not have an official EC number, and the reactions are not expected to have an EC number assigned because of a lack of articles published on enzyme assays. To predict the EC number of a non-classified enzymatic reaction, we focus on the structural similarity of its substrate and product to the substrate and product of reactions that have been classified. Results: We propose a new method to assign EC numbers using a maximum common substructure algorithm, mutual information and a support vector machine, termed the Enzyme COmmission numbers Handler (ECOH). A jack-knife test shows that the sensitivity, precision and accuracy of the method in predicting the first three digits of the official EC number (i.e. the EC sub-subclass) are 86.1%, 87.4 % and 99...
Methods of Information in Medicine, 2005
Summary Objectives: The rapid progress of life-scientific research has the potential to dramatica... more Summary Objectives: The rapid progress of life-scientific research has the potential to dramatically change the paradigm of drug discovery. Efficient utilization of life-scientific resources, i.e., databases and analytic software tools, poses a challenging issue with regard to the reduction of time and cost in the drug discovery process. In this paper, a variety of heterogeneous Web-based life-scientific resources are integrated toward the improvement of drug discovery performance. Methods: For the integration of heterogeneous life-scientific resources, a database federation technique based on three-layer architecture has been utilized. With the federation technique, life-scientific resources are integrated step by step through database layers, database integration layers and analysis layers to encapsulate complexity and heterogeneity. In this study, we have taken advantage of the latest Grid technology based on OGSA (Open Grid Services Architecture) for the implementation of our ap...
Motivation: The enzyme nomenclature system, commonly known as the enzyme commission (EC) number, ... more Motivation: The enzyme nomenclature system, commonly known as the enzyme commission (EC) number, plays a key role in classi-fying and predicting enzymatic reactions. However, numerous reac-tions have been described in various pathways that do not have an official EC number, and the reactions are not expected to have an EC number assigned because of a lack of articles published on enzyme assays. To predict the EC number of a non-classified en-zymatic reaction, we focus on the structural similarity of its substrate and product to the substrate and product of reactions that have been classified. Results: We propose a new method to assign EC numbers using a maximum common substructure algorithm, mutual information, and a support vector machine, termed the Enzyme COmmission num-bers Handler (ECOH). A jack-knife test shows that the sensitivity, precision, and accuracy of the method in predicting the first three digits of the official EC number (i.e. the EC sub-subclass) are 86.1%, 87.4%, ...
Abstract. The rapid progress of biotechnology provides an increasing number of life science datab... more Abstract. The rapid progress of biotechnology provides an increasing number of life science databases. These databases have been operated and managed individually on the Internet. Under such a circumstance, it is needed to develop an infrastructure that allows to share information contained in these databases and to conduct research collaboration. Grid technology is an emerging technology for seamless and loose integration of diverse resources distributed on the Internet. In order to achieve federation of the heterogeneous databases, we have developed a system for supporting a drug discovery process using Globus Toolkit3/OGSA-DAI. As an essential part of the system, we introduce a protein-compound interaction search based on a meta-data bridging protein and compound information with their interaction types; such as, inhibitor, agonist, antagonist, etc. The effectiveness of our system is demonstrated by searching for the candidate compounds interacting with the glucocorticoid recepto...
Journal of Computational Biology, Feb 17, 2023
Genome-scale constraint-based metabolic networks play an important role in the simulation of grow... more Genome-scale constraint-based metabolic networks play an important role in the simulation of growth-coupled production, which means that cell growth and target metabolite production are simultaneously achieved. For growth-coupled production, a minimal reaction-network-based design is known to be effective. However, the obtained reaction networks often fail to be realized by gene deletions due to conflicts with gene-protein-reaction relations. Here, we developed gDel minRN that determines gene deletion strategies using mixed-integer linear programming to achieve growth-coupled production by repressing the maximum number of reactions via gene-protein-reaction relations. The results of computational experiments showed that gDel minRN could determine the core parts, which include only 30 to 55% of whole genes, for stoichiometrically feasible growth-coupled production for many target metabolites, which include useful vitamins such as biotin (vitamin B7), riboflavin (vitamin B2), and pantothenate (vitaminB5). Since gDel minRN calculates a constraint-based model of the minimum number of gene-associated reactions without conflict with gene-protein-reaction relations, it helps biological analysis of the core parts essential for growth-coupled production for each target metabolite. The source codes, implemented in MATLAB using CPLEX and COBRA Toolbox, are available on {{https://github.com/MetNetComp/gDel-minRN}}
Lecture Notes in Computer Science, 2022
PLOS ONE, Aug 12, 2020
BD5 is a new binary data format based on HDF5 (hierarchical data format version 5). It can be use... more BD5 is a new binary data format based on HDF5 (hierarchical data format version 5). It can be used for representing quantitative biological dynamics data obtained from bioimage informatics techniques and mechanobiological simulations. Biological Dynamics Markup Language (BDML) is an XML (Extensible Markup Language)-based open format that is also used to represent such data; however, it becomes difficult to access quantitative data in BDML files when the file size is large because parsing XML-based files requires large computational resources to first read the whole file sequentially into computer memory. BD5 enables fast random (i.e., direct) access to quantitative data on disk without parsing the entire file. Therefore, it allows practical reuse of data for understanding biological mechanisms underlying the dynamics.
Glycoconjugate Journal, Aug 14, 2012
Brine shrimp are primitive crustacean arthropodal model organisms, second to daphnia, which can s... more Brine shrimp are primitive crustacean arthropodal model organisms, second to daphnia, which can survive in high-salinity environments. Their oviposited cysts, cuticlecovered diapausing eggs, are highly resistant to dryness. To elucidate specialties of brine shrimp, this study characterized glycosphingolipids, which are signal transductionassociated material. A group of novel and complex fucosyl glycosphingolipids were separated and identified from cysts of the brine shrimp Artemia franciscana by repeated lipid extraction, alkaline methanolysis, acid treatment, successive column chromatography, and post-source decay measurements by matrix-assisted laser desorption/ionization time-offlight mass spectrometry. Structures of the glycosphingolipids were elucidated by conventional structural characterization and mass spectrometry, and the compounds were identified as GlcNAcβ1-3GalNAcβ1-4(GlcNAcα1-2Fucα1-3)GlcNAcβ1-3Manβ1-4Glcβ1-Cer, GalNAcβ1-4(Fucα1-3)GlcNAcβ 1-3GalNAcβ 1-4(GlcNAcα 1-2Fucα 1-3)GlcNAcβ1-3Manβ1-4Glcβ1-Cer, and GalNAcβ1-4 (GlcNAcα 1-2Fucα 1-3)GlcNAcβ 1-3GalNAcβ 1-4 (GlcNAcα1-2Fucα1-3)GlcNAcβ1-3Manβ1-4Glcβ1-Cer. These compounds also contained a branching, non-arthroseries disaccharide with an α-GlcNAc terminus, similar to that found in a previously reported ceramide hexasaccharide (III 3 (GlcNAcα2Fucα)-At 4 Cer). The glycans within these complex GSLs are longer than reported glycans of the animal kingdom containing α-GlcNAc terminus. These complex GSLs as well as the longest GSL with ten sugar residues, ceramide decasaccharide (CDeS), contain the fucosylated LacdiNAc sequence reported to associate with parasitism/ immunosuppression and the α-GlcNAc terminus reported to show a certain antibacterial effect in other reports. CDeS, the longest GSL of this species, was found in the highest amount, which indicates that CDeS may be functionally important. Keywords Sphingosine. Fucomannolipid. Terminal α-N-acetylglucosamine residue. Structure characterization. Branchiopoda. Dormant cyst Abbreviations CDeS Ceramide decasaccharide CHpS Ceramide heptasaccharide CHS Ceramide hexasaccharide CNS Ceramide nonasaccharide COS Ceramide octasaccharide GC Gas chromatography GSL Glycosphingolipid 1 H-NMR Proton nuclear magnetic resonance HPTLC High-performance thin-layer chromatography MALDI-TOF MS Matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry Electronic supplementary material The online version of this article
Lecture Notes in Computer Science, 2022
Ipsj Transactions on Bioinformatics, 2023
Identifying factors that contribute to microbial growth is important for realizing efficient prod... more Identifying factors that contribute to microbial growth is important for realizing efficient production of useful substrates. Our objective was to predict unknown metabolic pathways from experimental time-series data in model organisms such as Escherichia coli. We focused on a previous method that replaces the computation of auto-regression in the Granger causality test with non-parametric multiplicative regression (NPMR) to allow inferences on noisy and nonlinear data. We then proposed a new causal inference method that creates a multi-dimensional space based on the error between the time series predicted by NPMR and the original time series. We confirmed that the inference accuracy of the proposed method outperforms that of NPMR by 50% using short time series generated by coupled logistic equations, which allows for adjustment of the strength of the causal relationship. The proposed method was applied to simulation data obtained from a kinetic model for glycolysis in E. coli and achieved 61% accuracy.
The Japanese Biochemical Society/The Molecular Biology Society of Japan, Nov 2, 2015
Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme, 2001
Genome Informatics Series, 1999
The MINL problem is a problem that finds a minimum and reduced set of patterns explaining a given... more The MINL problem is a problem that finds a minimum and reduced set of patterns explaining a given set of positive example strings. By restricting the number of patterns to be a fixed constant in advance, a polynomial time algorithm that solves this problem is known [1]. This algorithm is applicable to determining gene clusters based on functional classification if genes having the same function are expressed with the same character. However, since gene function is typically classified hierarchically, the above algorithm can only be applied on a single level of the classification hierarchy. In this paper, we extend the MINL problem to cover hierarchical classifications, and propose a novel polynomial time algorithm utilizing entropy to solve the extended problem. The effectiveness of our method is demonstrated by applying the method to a gene cluster analysis on 9 complete genomes.
Motivation: The enzyme nomenclature system, commonly known as the enzyme commission (EC) number, ... more Motivation: The enzyme nomenclature system, commonly known as the enzyme commission (EC) number, plays a key role in classifying and predicting enzymatic reactions. However, numerous reactions have been described in various pathways that do not have an official EC number, and the reactions are not expected to have an EC number assigned because of a lack of articles published on enzyme assays. To predict the EC number of a non-classified enzymatic reaction, we focus on the structural similarity of its substrate and product to the substrate and product of reactions that have been classified. Results: We propose a new method to assign EC numbers using a maximum common substructure algorithm, mutual information and a support vector machine, termed the Enzyme COmmission numbers Handler (ECOH). A jack-knife test shows that the sensitivity, precision and accuracy of the method in predicting the first three digits of the official EC number (i.e. the EC sub-subclass) are 86.1%, 87.4 % and 99...
Methods of Information in Medicine, 2005
Summary Objectives: The rapid progress of life-scientific research has the potential to dramatica... more Summary Objectives: The rapid progress of life-scientific research has the potential to dramatically change the paradigm of drug discovery. Efficient utilization of life-scientific resources, i.e., databases and analytic software tools, poses a challenging issue with regard to the reduction of time and cost in the drug discovery process. In this paper, a variety of heterogeneous Web-based life-scientific resources are integrated toward the improvement of drug discovery performance. Methods: For the integration of heterogeneous life-scientific resources, a database federation technique based on three-layer architecture has been utilized. With the federation technique, life-scientific resources are integrated step by step through database layers, database integration layers and analysis layers to encapsulate complexity and heterogeneity. In this study, we have taken advantage of the latest Grid technology based on OGSA (Open Grid Services Architecture) for the implementation of our ap...
Motivation: The enzyme nomenclature system, commonly known as the enzyme commission (EC) number, ... more Motivation: The enzyme nomenclature system, commonly known as the enzyme commission (EC) number, plays a key role in classi-fying and predicting enzymatic reactions. However, numerous reac-tions have been described in various pathways that do not have an official EC number, and the reactions are not expected to have an EC number assigned because of a lack of articles published on enzyme assays. To predict the EC number of a non-classified en-zymatic reaction, we focus on the structural similarity of its substrate and product to the substrate and product of reactions that have been classified. Results: We propose a new method to assign EC numbers using a maximum common substructure algorithm, mutual information, and a support vector machine, termed the Enzyme COmmission num-bers Handler (ECOH). A jack-knife test shows that the sensitivity, precision, and accuracy of the method in predicting the first three digits of the official EC number (i.e. the EC sub-subclass) are 86.1%, 87.4%, ...
Abstract. The rapid progress of biotechnology provides an increasing number of life science datab... more Abstract. The rapid progress of biotechnology provides an increasing number of life science databases. These databases have been operated and managed individually on the Internet. Under such a circumstance, it is needed to develop an infrastructure that allows to share information contained in these databases and to conduct research collaboration. Grid technology is an emerging technology for seamless and loose integration of diverse resources distributed on the Internet. In order to achieve federation of the heterogeneous databases, we have developed a system for supporting a drug discovery process using Globus Toolkit3/OGSA-DAI. As an essential part of the system, we introduce a protein-compound interaction search based on a meta-data bridging protein and compound information with their interaction types; such as, inhibitor, agonist, antagonist, etc. The effectiveness of our system is demonstrated by searching for the candidate compounds interacting with the glucocorticoid recepto...