論文 - 舟橋　啓

The Systems Biology Graphical Notation

舟橋 啓

NATURE BIOTECHNOLOGY 27 （ 8 ） 735-741 - 741 2009年08月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1087-0156

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Using process diagrams for the graphical representation of biological networks

Kitano Hiroaki, Funahashi Akira, Matsuoka Yukiko, Oda Kanae

Nature Biotechnology 23 （ 8 ） 961 - 966 2005年08月

ISSN  1087-0156

　概要を見る

<p>With the increased interest in understanding biological networks, such as protein-protein interaction networks and gene regulatory networks, methods for representing and communicating such networks in both human- and machine-readable form have become increasingly important. Although there has been significant progress in machine-readable representation of networks, as exemplified by the Systems Biology Mark-up Language (SBML) (http://www.sbml.org) issues in human-readable representation have been largely ignored. This article discusses human-readable diagrammatic representations and proposes a set of notations that enhances the formality and richness of the information represented. The process diagram is a fully state transition-based diagram that can be translated into machine-readable forms such as SBML in a straightforward way. It is supported by CellDesigner, a diagrammatic network editing software (http://www.celldesigner. org/), and has been used to represent a variety of networks of various sizes (from only a few components to several hundred components).</p>

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A comprehensive pathway map of epidermal growth factor receptor signaling

Oda Kanae, Matsuoka Yukiko, Funahashi Akira, Kitano Hiroaki

MOLECULAR SYSTEMS BIOLOGY 1 （ 1 ） 1-17 2005年05月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1744-4292

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3D convolutional neural networks-based segmentation to acquire quantitative criteria of the nucleus during mouse embryogenesis

Tokuoka Y., Yamada T.G., Mashiko D., Ikeda Z., Hiroi N.F., Kobayashi T.J., Yamagata K., Funahashi A.

npj Systems Biology and Applications （npj Systems Biology and Applications）  6 （ 1 ） 32 2020年12月

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

© 2020, The Author(s). During embryogenesis, cells repeatedly divide and dynamically change their positions in three-dimensional (3D) space. A robust and accurate algorithm to acquire the 3D positions of the cells would help to reveal the mechanisms of embryogenesis. To acquire quantitative criteria of embryogenesis from time-series 3D microscopic images, image processing algorithms such as segmentation have been applied. Because the cells in embryos are considerably crowded, an algorithm to segment individual cells in detail and accurately is needed. To quantify the nuclear region of every cell from a time-series 3D fluorescence microscopic image of living cells, we developed QCANet, a convolutional neural network-based segmentation algorithm for 3D fluorescence bioimages. We demonstrated that QCANet outperformed 3D Mask R-CNN, which is currently considered as the best algorithm of instance segmentation. We showed that QCANet can be applied not only to developing mouse embryos but also to developing embryos of two other model species. Using QCANet, we were able to extract several quantitative criteria of embryogenesis from 11 early mouse embryos. We showed that the extracted criteria could be used to evaluate the differences between individual embryos. This study contributes to the development of fundamental approaches for assessing embryogenesis on the basis of extracted quantitative criteria.

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BioSimulators: a central registry of simulation engines and services for recommending specific tools

Shaikh B., Smith L.P., Vasilescu D., Marupilla G., Wilson M., Agmon E., Agnew H., Andrews S.S., Anwar A., Beber M.E., Bergmann F.T., Brooks D., Brusch L., Calzone L., Choi K., Cooper J., Detloff J., Drawert B., Dumontier M., Ermentrout G.B., Faeder J.R., Freiburger A.P., Fröhlich F., Funahashi A., Garny A., Gennari J.H., Gleeson P., Goelzer A., Haiman Z., Hasenauer J., Hellerstein J.L., Hermjakob H., Hoops S., Ison J.C., Jahn D., Jakubowski H.V., Jordan R., Kalaš M., König M., Liebermeister W., Sheriff R.S.M., Mandal S., McDougal R., Medley J.K., Mendes P., Müller R., Myers C.J., Naldi A., Nguyen T.V.N., Nickerson D.P., Olivier B.G., Patoliya D., Paulevé L., Petzold L.R., Priya A., Rampadarath A.K., Rohwer J.M., Saglam A.S., Singh D., Sinha A., Snoep J., Sorby H., Spangler R., Starruß J., Thomas P.J., Van Niekerk D., Weindl D., Zhang F., Zhukova A., Goldberg A.P., Schaff J.C., Blinov M.L., Sauro H.M., Moraru I.I., Karr J.R.

Nucleic Acids Research （Nucleic Acids Research）  50 （ W1 ） W108 - W114 2022年07月

共著, 査読有り,  ISSN  03051048

　概要を見る

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations.

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COVID19 Disease Map, a computational knowledge repository of virus–host interaction mechanisms

Ostaszewski M., Niarakis A., Mazein A., Kuperstein I., Phair R., Orta-Resendiz A., Singh V., Aghamiri S.S., Acencio M.L., Glaab E., Ruepp A., Fobo G., Montrone C., Brauner B., Frishman G., Monraz Gómez L.C., Somers J., Hoch M., Kumar Gupta S., Scheel J., Borlinghaus H., Czauderna T., Schreiber F., Montagud A., Ponce de Leon M., Funahashi A., Hiki Y., Hiroi N., Yamada T.G., Dräger A., Renz A., Naveez M., Bocskei Z., Messina F., Börnigen D., Fergusson L., Conti M., Rameil M., Nakonecnij V., Vanhoefer J., Schmiester L., Wang M., Ackerman E.E., Shoemaker J.E., Zucker J., Oxford K., Teuton J., Kocakaya E., Summak G.Y., Hanspers K., Kutmon M., Coort S., Eijssen L., Ehrhart F., Rex D.A.B., Slenter D., Martens M., Pham N., Haw R., Jassal B., Matthews L., Orlic-Milacic M., Senff Ribeiro A., Rothfels K., Shamovsky V., Stephan R., Sevilla C., Varusai T., Ravel J.M., Fraser R., Ortseifen V., Marchesi S., Gawron P., Smula E., Heirendt L., Satagopam V., Wu G., Riutta A., Golebiewski M., Owen S., Goble C., Hu X., Overall R.W., Maier D., Bauch A., Gyori B.M., Bachman J.A., Vega C., Grouès V., Vazquez M., Porras P., Licata L., Iannuccelli M., Sacco F., Nesterova A., Yuryev A., de Waard A., Turei D., Luna A., Babur O.

Molecular Systems Biology （Molecular Systems Biology）  17 （ 10 ） e10387 2021年10月

共著, 査読有り,  ISSN  1744-4292

　概要を見る

We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.

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The principles of whole-cell modeling

Karr Jonathan R., Takahashi Koichi, Funahashi Akira

CURRENT OPINION IN MICROBIOLOGY （Elsevier {BV}）  27   18 - 24 2015年10月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1369-5274

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<p>Whole-cell models which comprehensively predict how phenotypes emerge from genotype promise to enable rational bioengineering and precision medicine. Here, we outline the key principles of whole-cell modeling which have emerged from our work developing bacterial whole-cell models: single-cellularity; functional, genetic, molecular, and temporal completeness; biophysical realism including temporal dynamics and stochastic variation; species-specificity; and model integration and reproducibility. We also outline the whole-cell model construction process, highlighting existing resources. Numerous challenges remain to achieving fully complete models including developing new experimental tools to more completely characterize cells and developing a strong theoretical understanding of hybrid mathematics. Solving these challenges requires collaboration among computational and experimental biologists, biophysicists, biochemists, applied mathematicians, computer scientists, and software engineers.</p>

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Acceleration of discrete stochastic biochemical simulation using GPGPU

Sumiyoshi Kei, Hirata Kazuki, Hiroi Noriko, Funahashi Akira

FRONTIERS IN PHYSIOLOGY 6   155 - 169 2015年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1664-042X

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SBML Level 3: an extensible format for the exchange and reuse of biological models

Keating Sarah M., Waltemath Dagmar, Koenig Matthias, Zhang Fengkai, Draeger Andreas, Chaouiya Claudine, Bergmann Frank T., Finney Andrew, Gillespie Colin S., Helikar Tomas, Hoops Stefan, Malik-Sheriff Rahuman S., Moodie Stuart L., Moraru Ion I., Myers Chris J., Naldi Aurelien, Olivier Brett G., Sahle Sven, Schaff James C., Smith Lucian P., Swat Maciej J., Thieffry Denis, Watanabe Leandro, Wilkinson Darren J., Blinov Michael L., Begley Kimberly, Faeder James R., Gomez Harold F., Hamm Thomas M., Inagaki Yuichiro, Liebermeister Wolfram, Lister Allyson L., Lucio Daniel, Mjolsness Eric, Proctor Carole J., Raman Karthik, Rodriguez Nicolas, Shaffer Clifford A., Shapiro Bruce E., Stelling Joerg, Swainston Neil, Tanimura Naoki, Wagner John, Meier-Schellersheim Martin, Sauro Herbert M., Palsson Bernhard, Bolouri Hamid, Kitano Hiroaki, Funahashi Akira, Hermjakob Henning, Doyle John C., Hucka Michael

Molecular Systems Biology 16 （ 8 ） e9110 2020年08月

共著, 査読有り,  ISSN  1744-4292

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High-speed microscopy with an electrically tunable lens to image the dynamics of in vivo molecular complexes

Nakai Yuichiro, Ozeki Mitsunori, Hiraiwa Takumi, Tanimoto Ryuichi, Funahashi Akira, Hiroi Noriko, Taniguchi Atsushi, Nonaka Shigenori, Boilot Viviane, Shrestha Roshan, Clark Joanna, Tamura Naoka, Draviam Viji M., Oku Hiromasa

REVIEW OF SCIENTIFIC INSTRUMENTS 86 （ 1 ） 013707 2015年01月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0034-6748

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Symbolic Integration by Integrating Learning Models With Different Strengths and Weaknesses

Kubota H., Tokuoka Y., Yamada T.G., Funahashi A.

IEEE Access （IEEE Access）  10   47000 - 47010 2022年

共著, 査読有り,  ISSN  2169-3536

　概要を見る

Integration is indispensable, not only in mathematics, but also in a wide range of other fields. A deep learning method has recently been developed and shown to be capable of integrating mathematical functions that could not previously be integrated on a computer. However, that method treats integration as equivalent to natural language translation and does not reflect mathematical information. In this study, we adjusted the learning model to take mathematical information into account and developed a wide range of learning models that learn the order of numerical operations more robustly. In this way, we achieved a 98.80% correct answer rate with symbolic integration, a higher rate than that of any existing method. We judged the correctness of the integration based on whether the derivative of the primitive function was consistent with the integrand. By building an integrated model based on this strategy, we achieved a 99.79% rate of correct answers with symbolic integration. In summary, we have developed a more accurate method of selecting the correct model than the existing method by judging the result of symbolic integration based on whether the output of the model equals the input formula when the output is differentiated.

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Identification of a master transcription factor and a regulatory mechanism for desiccation tolerance in the anhydrobiotic cell line Pv11

Yamada T.G., Hiki Y., Hiroi N.F., Shagimardanova E., Gusev O., Cornette R., Kikawada T., Funahashi A.

PLoS ONE （PLoS ONE）  15 （ 3 ） e0230218 2020年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1932-6203

　概要を見る

Copyright: © 2020 Yamada et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Water is essential for living organisms. Terrestrial organisms are incessantly exposed to the stress of losing water, desiccation stress. Avoiding the mortality caused by desiccation stress, many organisms acquired molecular mechanisms to tolerate desiccation. Larvae of the African midge, Polypedilum vanderplanki, and its embryonic cell line Pv11 tolerate desiccation stress by entering an ametabolic state, anhydrobiosis, and return to active life after rehydration. The genes related to desiccation tolerance have been comprehensively analyzed, but transcriptional regulatory mechanisms to induce these genes after desiccation or rehydration remain unclear. Here, we comprehensively analyzed the gene regulatory network in Pv11 cells and compared it with that of Drosophila melanogaster, a desiccation sensitive species. We demonstrated that nuclear transcription factor Y subunit gamma-like, which is important for drought stress tolerance in plants, and its transcriptional regulation of downstream positive feedback loops have a pivotal role in regulating various anhydrobiosis-related genes. This study provides an initial insight into the systemic mechanism of desiccation tolerance.

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Predicting the future direction of cell movement with convolutional neural networks.

Nishimoto S, Tokuoka Y, Yamada TG, Hiroi NF, Funahashi A

PloS one （PLoS ONE）  14 （ 9 ） e0221245 2019年09月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1932-6203

　概要を見る

© 2019 Nishimoto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Image-based deep learning systems, such as convolutional neural networks (CNNs), have recently been applied to cell classification, producing impressive results; however, application of CNNs has been confined to classification of the current cell state from the image. Here, we focused on cell movement where current and/or past cell shape can influence the future cell movement. We demonstrate that CNNs prospectively predicted the future direction of cell movement with high accuracy from a single image patch of a cell at a certain time. Furthermore, by visualizing the image features that were learned by the CNNs, we could identify morphological features, e.g., the protrusions and trailing edge that have been experimentally reported to determine the direction of cell movement. Our results indicate that CNNs have the potential to predict the future direction of cell movement from current cell shape, and can be used to automatically identify those morphological features that influence future cell movement.

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Detection of Temperature Difference in Neuronal Cells

Tanimoto Ryuichi, Hiraiwa Takumi, Nakai Yuichiro, Shindo Yutaka, Oka Kotaro, Hiroi Noriko, Funahashi Akira

SCIENTIFIC REPORTS 6   22071 2016年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2045-2322

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Metabolic Tug-of-War between Glycolysis and Translation Revealed by Biochemical Reconstitution

Sato G., Kinoshita S., Yamada T.G., Arai S., Kitaguchi T., Funahashi A., Doi N., Fujiwara K.

ACS Synthetic Biology （ACS Synthetic Biology）  13 （ 5 ） 1572 - 1581 2024年05月

共著, 査読有り,  ISSN  2161-5063

　概要を見る

Inside cells, various biological systems work cooperatively for homeostasis and self-replication. These systems do not work independently as they compete for shared elements like ATP and NADH. However, it has been believed that such competition is not a problem in codependent biological systems such as the energy-supplying glycolysis and the energy-consuming translation system. In this study, we biochemically reconstituted the coupling system of glycolysis and translation using purified elements and found that the competition for ATP between glycolysis and protein synthesis interferes with their coupling. Both experiments and simulations revealed that this interference is derived from a metabolic tug-of-war between glycolysis and translation based on their reaction rates, which changes the threshold of the initial substrate concentration for the success coupling. By the metabolic tug-of-war, translation energized by strong glycolysis is facilitated by an exogenous ATPase, which normally inhibits translation. These findings provide chemical insights into the mechanism of competition among biological systems in living cells and provide a framework for the construction of synthetic metabolism in vitro.

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Switching from weak to strong cortical attachment of microtubules accounts for the transition from nuclear centration to spindle elongation in metazoans

Tada S., Yamazaki Y., Yamamoto K., Fujii K., Yamada T.G., Hiroi N.F., Kimura A., Funahashi A.

Heliyon （Heliyon）  10 （ 3 ） e25494 2024年02月

共著, 査読有り,  ISSN  24058440

　概要を見る

The centrosome is a major microtubule organizing center in animal cells. The position of the centrosomes inside the cell is important for cell functions such as cell cycle, and thus should be tightly regulated. Theoretical models based on the forces generated along the microtubules have been proposed to account for the dynamic movements of the centrosomes during the cell cycle. These models, however, often adopted inconsistent assumptions to explain distinct but successive movements, thus preventing a unified model for centrosome positioning. For the centration of the centrosomes, weak attachment of the astral microtubules to the cell cortex was assumed. In contrast, for the separation of the centrosomes during spindle elongation, strong attachment was assumed. Here, we mathematically analyzed these processes at steady state and found that the different assumptions are proper for each process. We experimentally validated our conclusion using nematode and sea urchin embryos by manipulating their shapes. Our results suggest the existence of a molecular mechanism that converts the cortical attachment from weak to strong during the transition from centrosome centration to spindle elongation.

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SBML level 3 package: spatial processes, version 1, release 1

Schaff James C., Lakshminarayana Anuradha, Murphy Robert F., Bergmann Frank T., Funahashi Akira, Sullivan Devin P., Smith Lucian P.

Journal of Integrative Bioinformatics 20 （ 1 ）  2023年03月

共著, 査読有り

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Titanium Culture Vessel Presenting Temperature Gradation for the Thermotolerance Estimation of Cells

Imashiro C., Jin Y., Hayama M., Yamada T.G., Funahashi A., Sakaguchi K., Umezu S., Komotori J.

Cyborg and Bionic Systems （Cyborg and Bionic Systems）  4   0049 2023年

共著, 査読有り,  ISSN  20971087

　概要を見る

Hyperthermia can be induced to exploit the thermal intolerance of cancer cells, which is worse than that of normal cells, as a potential noninvasive cancer treatment. To develop an effective hyperthermia treatment, thermal cytotoxicity of cells should be comprehensively investigated. However, to conduct such investigations, the culture temperature must be accurately regulated. We previously reported a culture system in which the culture temperature could be accurately regulated by employing metallic culture vessels. However, appropriate temperature conditions for hyperthermia depend on the cell species. Consequently, several experiments need to be conducted, which is a bottleneck of inducing hyperthermia. Hence, we developed a cell culture system with temperature gradation on a metallic culture surface. Michigan Cancer Foundation-7 cells and normal human dermal fibroblasts were used as cancer and normal cell models, respectively. Normal cells showed stronger thermal tolerance; this was because the novel system immediately exhibited a temperature gradation. Thus, the developed culture system can be used to investigate the optimum thermal conditions for effective hyperthermia treatment. Furthermore, as the reactions of cultured cells can be effectively assessed with the present results, further research involving the thermal stimulation of cells is possible.

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Drug-target identification in COVID-19 disease mechanisms using computational systems biology approaches

Niarakis A., Ostaszewski M., Mazein A., Kuperstein I., Kutmon M., Gillespie M.E., Funahashi A., Acencio M.L., Hemedan A., Aichem M., Klein K., Czauderna T., Burtscher F., Yamada T.G., Hiki Y., Hiroi N.F., Hu F., Pham N., Ehrhart F., Willighagen E.L., Valdeolivas A., Dugourd A., Messina F., Esteban-Medina M., Peña-Chilet M., Rian K., Soliman S., Aghamiri S.S., Puniya B.L., Naldi A., Helikar T., Singh V., Fernández M.F., Bermudez V., Tsirvouli E., Montagud A., Noël V., Ponce-de-Leon M., Maier D., Bauch A., Gyori B.M., Bachman J.A., Luna A., Piñero J., Furlong L.I., Balaur I., Rougny A., Jarosz Y., Overall R.W., Phair R., Perfetto L., Matthews L., Rex D.A.B., Orlic-Milacic M., Gomez L.C.M., De Meulder B., Ravel J.M., Jassal B., Satagopam V., Wu G., Golebiewski M., Gawron P., Calzone L., Beckmann J.S., Evelo C.T., D’Eustachio P., Schreiber F., Saez-Rodriguez J., Dopazo J., Kuiper M., Valencia A., Wolkenhauer O., Kitano H., Barillot E., Auffray C., Balling R., Schneider R.

Frontiers in Immunology （Frontiers in Immunology）  14   1282859 2023年

共著, 査読有り,  ISSN  1664-3224

　概要を見る

Introduction: The COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. Methods: Extensive community work allowed an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework can link biomolecules from omics data analysis and computational modelling to dysregulated pathways in a cell-, tissue- or patient-specific manner. Drug repurposing using text mining and AI-assisted analysis identified potential drugs, chemicals and microRNAs that could target the identified key factors. Results: Results revealed drugs already tested for anti-COVID-19 efficacy, providing a mechanistic context for their mode of action, and drugs already in clinical trials for treating other diseases, never tested against COVID-19. Discussion: The key advance is that the proposed framework is versatile and expandable, offering a significant upgrade in the arsenal for virus-host interactions and other complex pathologies.

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Development of non-bias phenotypic drug screening for cardiomyocyte hypertrophy by image segmentation using deep learning

Komuro J., Tokuoka Y., Seki T., Kusumoto D., Hashimoto H., Katsuki T., Nakamura T., Akiba Y., Kuoka T., Kimura M., Yamada T., Fukuda K., Funahashi A., Yuasa S.

Biochemical and Biophysical Research Communications （Biochemical and Biophysical Research Communications）  632   181 - 188 2022年12月

共著, 査読有り,  ISSN  0006291X

　概要を見る

The number of patients with heart failure and related deaths is rapidly increasing worldwide, making it a major problem. Cardiac hypertrophy is a crucial preliminary step in heart failure, but its treatment has not yet been fully successful. In this study, we established a system to evaluate cardiomyocyte hypertrophy using a deep learning-based high-throughput screening system and identified drugs that inhibit it. First, primary cultured cardiomyocytes from neonatal rats were stimulated by both angiotensin II and endothelin-1, and cellular images were captured using a phase-contrast microscope. Subsequently, we used a deep learning model for instance segmentation and established a system to automatically and unbiasedly evaluate the cardiomyocyte size and perimeter. Using this system, we screened 100 FDA-approved drugs library and identified 12 drugs that inhibited cardiomyocyte hypertrophy. We focused on ezetimibe, a cholesterol absorption inhibitor, that inhibited cardiomyocyte hypertrophy in a dose-dependent manner in vitro. Additionally, ezetimibe improved the cardiac dysfunction induced by pressure overload in mice. These results suggest that the deep learning-based system is useful for the evaluation of cardiomyocyte hypertrophy and drug screening, leading to the development of new treatments for heart failure.

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人工知能および高速レーザー照射システムの統合による高品質ヒト心筋細胞の作製と臨床応用

遠山 周吾, 舟橋 啓

福田記念医療技術振興財団情報 （(公財)福田記念医療技術振興財団）   （ 35 ） 181 - 186 2022年12月

共著, 査読有り

　概要を見る

自動高速レーザー照射システムにより目的外細胞を除去し、ロット差の極めて少ない心筋細胞を作製するための前段階として、AIによる機械学習を用いて目的細胞と目的外細胞を識別する手法を開発することを目的とした。自動化心筋細胞拍動評価システムを用いて培養皿上で拍動する心筋細胞の動画を効率よく撮影し、拍動方向のベクトル解析により心筋領域を同定することで非心筋細胞との領域の判別が可能となった。セグメンテーション精度と心筋領域の割合の関係を定性的に確認すると、心筋領域の割合が高い画像のセグメンテーション精度は約80%に達したが、心筋領域の割合が低い画像のセグメンテーションは約1%と非常に低いことが確認された。

Intercellular interaction mechanisms promote diversity in intracellular ATP concentration in Escherichia coli populations

Nakatani R.J., Itabashi M., Yamada T.G., Hiroi N.F., Funahashi A.

Scientific Reports （Scientific Reports）  12 （ 1 ） 17946 2022年12月

共著, 査読有り

　概要を見る

In fluctuating environments, many microorganisms acquire phenotypic heterogeneity as a survival tactic to increase the likelihood of survival of the overall population. One example of this interindividual heterogeneity is the diversity of ATP concentration among members of Escherichia coli populations under glucose deprivation. Despite the importance of such environmentally driven phenotypic heterogeneity, how the differences in intracellular ATP concentration emerge among individual E. coli organisms is unknown. In this study, we focused on the mechanism through which individual E. coli achieve high intracellular ATP concentrations. First, we measured the ATP retained by E. coli over time when cultured at low (0.1 mM) and control (22.2 mM) concentrations of glucose and obtained the chronological change in ATP concentrations. Then, by comparing these chronological change of ATP concentrations and analyzing whether stochastic state transitions, periodic oscillations, cellular age, and intercellular communication—which have been reported as molecular biological mechanisms for generating interindividual heterogeneity—are involved, we showed that the appearance of high ATP-holding individuals observed among E. coli can be explained only by intercellular transmission. By performing metabolomic analysis of post-culture medium, we revealed a significant increase in the ATP, especially at low glucose, and that the number of E. coli that retain significantly higher ATP can be controlled by adding large amounts of ATP to the medium, even in populations cultured under control glucose concentrations. These results reveal for the first time that ATP-mediated intercellular transmission enables some individuals in E. coli populations grown at low glucose to retain large amounts of ATP.

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An explainable deep learning-based algorithm with an attention mechanism for predicting the live birth potential of mouse embryos

Tokuoka Y., Yamada T.G., Mashiko D., Ikeda Z., Kobayashi T.J., Yamagata K., Funahashi A.

Artificial Intelligence in Medicine （Artificial Intelligence in Medicine）  134   102432 2022年12月

共著, 査読有り,  ISSN  09333657

　概要を見る

In assisted reproductive technology (ART), embryos produced by in vitro fertilization (IVF) are graded according to their live birth potential, and high-grade embryos are preferentially transplanted. However, rates of live birth following clinical ART remain low worldwide. Grading is based on the embryo shape at a limited number of stages and does not consider the shape of embryos and intracellular structures, e.g., nuclei, at various stages important for normal embryogenesis. Here, we developed a Normalized Multi-View Attention Network (NVAN) that directly predicts live birth potential from the nuclear structure in live-cell fluorescence images of mouse embryos from zygote to across a wide range of stages. The input is morphological features of cell nuclei, which were extracted as multivariate time-series data by using the segmentation algorithm for mouse embryos. The classification accuracy of our method (83.87%) greatly exceeded that of existing machine-learning methods and that of visual inspection by embryo culture specialists. Our method also has a new attention mechanism that allows us to determine which values of multivariate time-series data, used to describe nuclear morphology, were the basis for the prediction. By visualizing the features that contributed most to the prediction of live birth potential, we found that the size and shape of the nucleus at the morula stage and at the time of cell division were important for live birth prediction. We anticipate that our method will help ART and developmental engineering as a new basic technology for IVF embryo selection.

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High quality genome assembly of the anhydrobiotic midge provides insights on a single chromosome-based emergence of extreme desiccation tolerance

Yoshida Y., Shaikhutdinov N., Kozlova O., Itoh M., Tagami M., Murata M., Nishiyori-Sueki H., Kojima-Ishiyama M., Noma S., Cherkasov A., Gazizova G., Nasibullina A., Deviatiiarov R., Shagimardanova E., Ryabova A., Yamaguchi K., Bino T., Shigenobu S., Tokumoto S., Miyata Y., Cornette R., Yamada T.G., Funahashi A., Tomita M., Gusev O., Kikawada T.

NAR Genomics and Bioinformatics （NAR Genomics and Bioinformatics）  4 （ 2 ） lqac029 2022年06月

共著, 査読有り

　概要を見る

Non-biting midges (Chironomidae) are known to inhabit a wide range of environments, and certain species can tolerate extreme conditions, where the rest of insects cannot survive. In particular, the sleeping chironomid Polypedilum vanderplanki is known for the remarkable ability of its larvae to withstand almost complete desiccation by entering a state called anhydrobiosis. Chromosome numbers in chironomids are higher than in other dipterans and this extra genomic resource might facilitate rapid adaptation to novel environments. We used improved sequencing strategies to assemble a chromosome-level genome sequence for P. vanderplanki for deep comparative analysis of genomic location of genes associated with desiccation tolerance. Using whole genome-based cross-species and intra-species analysis, we provide evidence for the unique functional specialization of Chromosome 4 through extensive acquisition of novel genes. In contrast to other insect genomes, in the sleeping chironomid a uniquely high degree of subfunctionalization in paralogous anhydrobiosis genes occurs in this chromosome, as well as pseudogenization in a highly duplicated gene family. Our findings suggest that the Chromosome 4 in Polypedilum is a site of high genetic turnover, allowing it to act as a 'sandbox' for evolutionary experiments, thus facilitating the rapid adaptation of midges to harsh environments.

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Temperature elevation detection in migrating cells

T Nakamura, J Sakamoto, K Okabe, A Taniguchi, TG Yamada, S Nonaka, ...

Optics Continuum （OSA Continuum）  1 （ 5 ） 1085 - 1097 2022年05月

共著, 査読有り

　概要を見る

Active and dynamic migration and deformation of cells are universal research targets in cell biology. The leader cells that develop at the wound edge are required to actively reorganize their structure for migration and deformation. Such active reorganization of cellular morphology possibly affects the temperature inside the cells via biochemical reactions. On the other hand, it is also possible that changes of intracellular temperature may first trigger and induce active migration and cellular deformation. Recent development of temperature sensors for cells enables the display of temperature difference between two adjacent cell populations such as the leader and follower cells around a wound. We used two different temperature measurement methods to check the temperature of leader and follower cells in a wound healing assay system and found that leader cells were 10° ∼ 101°C warmer than follower cells. We also confirmed that, when the cells were artificially warmed with an infrared laser, they started moving, and when the laser was stopped, the cells also stopped moving. These results suggest that the warmth of the leader cells is not simply a result of their active movement, but also can play the role of a trigger for cell migration and deformation. Our results shed light on the possibility that various observed cases of intracellular temperature increase may trigger associated biological phenomena.

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Neural Architecture Searchの探索空間削減を目指した深層学習モデルの部分構造解析

富山 護, 比企 佑介, 渋谷 優介, 徳岡 雄大, 山田 貴大, 舟橋 啓

人工知能学会全国大会論文集 （一般社団法人 人工知能学会）  JSAI2022 （ 0 ） 3Yin204 - 3Yin204 2022年

共著, 査読有り

　概要を見る

<p>近年、深層学習アーキテクチャを自動で設計するNeural Architecture Search (NAS)が注目されている。NASではアーキテクチャの部分構造の集合である探索空間から最適なアーキテクチャを決定する。しかしながら、現在提案されているNASの探索空間は計算量の膨大さゆえ限定されているため、高性能なアーキテクチャを見逃す可能性がある。そこで本研究は、タスク特異的な部分構造を有したアーキテクチャは高性能であると考え、NASの効率的な探索空間設計に資するタスク特異的な部分構造を同定する方法を開発した。 本手法はGraph Convolutional Networkを用いて既存のアーキテクチャのグラフ構造をタスクごとに分類する学習を行い、その分類に寄与した特徴を解析することで部分構造ごとにタスクへの特異度を出力する。実際に本手法により取得した部分構造ごとのタスクへの特異度と精度に有意な相関が確認できたことから、本手法により精度に貢献するタスク特異的な部分構造を同定可能であることが示された。本手法は、計算量を削減した上で高性能なアーキテクチャを決定可能なNASの開発に貢献することが期待される。</p>

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Cas9-mediated genome editing reveals a significant contribution of calcium signaling pathways to anhydrobiosis in Pv11 cells

Miyata Y., Fuse H., Tokumoto S., Hiki Y., Deviatiiarov R., Yoshida Y., Yamada T.G., Cornette R., Gusev O., Shagimardanova E., Funahashi A., Kikawada T.

Scientific Reports （Scientific Reports）  11 （ 1 ） 19698 2021年12月

共著, 査読有り,  ISSN  2045-2322

　概要を見る

Pv11 is an insect cell line established from the midge Polypedilum vanderplanki, whose larval form exhibits an extreme desiccation tolerance known as anhydrobiosis. Pv11 itself is also capable of anhydrobiosis, which is induced by trehalose treatment. Here we report the successful construction of a genome editing system for Pv11 cells and its application to the identification of signaling pathways involved in anhydrobiosis. Using the Cas9-mediated gene knock-in system, we established Pv11 cells that stably expressed GCaMP3 to monitor intracellular Ca2+ mobilization. Intriguingly, trehalose treatment evoked a transient increase in cytosolic Ca2+ concentration, and further experiments revealed that the calmodulin–calcineurin–NFAT pathway contributes to tolerance of trehalose treatment as well as desiccation tolerance, while the calmodulin–calmodulin kinase–CREB pathway conferred only desiccation tolerance on Pv11 cells. Thus, our results show a critical contribution of the trehalose-induced Ca2+ surge to anhydrobiosis and demonstrate temporally different roles for each signaling pathway.

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Sbmlwebapp: Web-based simulation, steady-state analysis, and parameter estimation of systems biology models

Yamada T.G., Ii K., König M., Feierabend M., Dräger A., Funahashi A.

Processes （Processes）  9 （ 10 ）  2021年10月

共著, 査読有り

　概要を見る

In systems biology, biological phenomena are often modeled by Ordinary Differential Equations (ODEs) and distributed in the de facto standard file format SBML. The primary analyses performed with such models are dynamic simulation, steady-state analysis, and parameter estimation. These methodologies are mathematically formalized, and libraries for such analyses have been published. Several tools exist to create, simulate, or visualize models encoded in SBML. However, setting up and establishing analysis environments is a crucial hurdle for non-modelers. Therefore, easy access to perform fundamental analyses of ODE models is a significant challenge. We developed SBMLWebApp, a web-based service to execute SBML-based simulation, steady-state analysis, and parameter estimation directly in the browser without the need for any setup or prior knowledge to address this issue. SBMLWebApp visualizes the result and numerical table of each analysis and provides a download of the results. SBMLWebApp allows users to select and analyze SBML models directly from the BioModels Database. Taken together, SBMLWebApp provides barrier-free access to an SBML analysis environment for simulation, steady-state analysis, and parameter estimation for SBML models. SBMLWebApp is implemented in Java™ based on an Apache Tomcat® web server using COPASI, the Systems Biology Simulation Core Library (SBSCL), and LibSBMLSim as simulation engines. SBMLWebApp is licensed under MIT with source code freely available. At the end of this article, the Data Availability Statement gives the internet links to the two websites to find the source code and run the program online.

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Genome-wide role of hsf1 in transcriptional regulation of desiccation tolerance in the anhydrobiotic cell line, pv11

Tokumoto S., Miyata Y., Deviatiiarov R., Yamada T.G., Hiki Y., Kozlova O., Yoshida Y., Cornette R., Funahashi A., Shagimardanova E., Gusev O., Kikawada T.

International Journal of Molecular Sciences （International Journal of Molecular Sciences）  22 （ 11 ）  2021年06月

共著, 査読有り,  ISSN  16616596

　概要を見る

The Pv11, an insect cell line established from the midge Polypedilum vanderplanki, is capa-ble of extreme hypometabolic desiccation tolerance, so-called anhydrobiosis. We previously discov-ered that heat shock factor 1 (HSF1) contributes to the acquisition of desiccation tolerance by Pv11 cells, but the mechanistic details have yet to be elucidated. Here, by analyzing the gene expression profiles of newly established HSF1-knockout and-rescue cell lines, we show that HSF1 has a ge-nome-wide effect on gene regulation in Pv11. The HSF1-knockout cells exhibit a reduced desiccation survival rate, but this is completely restored in HSF1-rescue cells. By comparing mRNA profiles of the two cell lines, we reveal that HSF1 induces anhydrobiosis-related genes, especially genes encoding late embryogenesis abundant proteins and thioredoxins, but represses a group of genes involved in basal cellular processes, thus promoting an extreme hypometabolism state in the cell. In addition, HSF1 binding motifs are enriched in the promoters of anhydrobiosis-related genes and we demonstrate binding of HSF1 to these promoters by ChIP-qPCR. Thus, HSF1 directly regulates the transcription of anhydrobiosis-related genes and consequently plays a pivotal role in the induction of anhydrobiotic ability in Pv11 cells.

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Electrical Field Chamber with Dinamically Adaptable Stimuli for Myocyte Orientation during Cultivation

Ramirez S.R.M., Yamada T., Funahashi A., Onoe H.

Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS) （Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS)）  2021-January   498 - 501 2021年01月

共著, 査読有り,  ISSN  10846999

　概要を見る

Tissue engineering is a promising technology for both its possible applications in the fields of regenerative medicine and medical research. One of its challenges is to create an environment which allows the cell cultures to develop correctly. This environment is far from static and normally is modified by the cells themselves. To this end, adaptable systems have to be developed to ensure a successful development of the in-vitro tissue. This research focuses on a system which is able to modify an external electrical stimulus on a culture chamber, during its cultivation. This system, through a variation of the stimulus direction, successfully improved the orientation of the developing myocytes.

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Control and measurement of nano/micro-space temperature that changes cellular behavior

Nakamura T., Saito T., Tanimoto R., Yamada T., Funahashi A., Taniguchi A., Nonaka S., Sakamoto J., Kamei Y., Tominaga M., Okabe K., Yanase Y., Kishi H., Hiroi N.F.

Optics InfoBase Conference Papers （Optics InfoBase Conference Papers）  2021年

共著, 査読有り

COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms

Ostaszewski Marek, Mazein Alexander, Gillespie Marc E., Kuperstein Inna, Niarakis Anna, Hermjakob Henning, Pico Alexander R., Willighagen Egon L., Evelo Chris T., Hasenauer Jan, Schreiber Falk, Draeger Andreas, Demir Emek, Wolkenhauer Olaf, Furlong Laura I, Barillot Emmanuel, Dopazo Joaquin, Orta-Resendiz Aurelio, Messina Francesco, Valencia Alfonso, Funahashi Akira, Kitano Hiroaki, Auffray Charles, Balling Rudi, Schneider Reinhard

Scientific Data 7 （ 1 ） 136 2020年05月

共著, 査読有り,  ISSN  2052-4463

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Neural differentiation dynamics controlled by multiple feedback loops in a comprehensive molecular interaction network

Iwasaki T., Takiguchi R., Hiraiwa T., Yamada T.G., Yamazaki K., Hiroi N.F., Funahashi A.

Processes （Processes）  8 （ 2 ）  2020年02月

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

© 2020 by the authors. Mathematical model simulation is a useful method for understanding the complex behavior of a living system. The construction of mathematical models using comprehensive information is one of the techniques of model construction. Such a comprehensive knowledge-based network tends to become a large-scale network. As a result, the variation of analyses is limited to a particular kind of analysis because of the size and complexity of the model. To analyze a large-scale regulatory network of neural differentiation, we propose a contractive method that preserves the dynamic behavior of a large network. The method consists of the following two steps: comprehensive network building and network reduction. The reduction phase can extract network loop structures from a large-scale regulatory network, and the subnetworks were combined to preserve the dynamics of the original large-scale network. We confirmed that the extracted loop combination reproduced the known dynamics of HES1 and ASCL1 before and after differentiation, including oscillation and equilibrium of their concentrations. The model also reproduced the effects of the overexpression and knockdown of the Id2 gene. Our model suggests that the characteristic change in HES1 and ASCL1 expression in the large-scale regulatory network is controlled by a combination of four feedback loops, including a large loop, which has not been focused on. The model extracted by our method has the potential to reveal the critical mechanisms of neural differentiation. The method is applicable to other biological events.

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Direct Cell Counting Using Macro-Scale Smartphone Images of Cell Aggregates

Chikahiro Imashiro and Yuta Tokuoka and Kaito Kikuhara and Takahiro G. Yamada and Kenjiro Takemura and Akira Funahashi

IEEE Access （Institute of Electrical and Electronics Engineers ({IEEE})）  8   170033 - 170043 2020年

共著, 査読有り,  ISSN  2169-3536

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Deep learning for non-invasive determination of the differentiation status of human neuronal cells by using phase-contrast photomicrographs

Ooka M., Tokuoka Y., Nishimoto S., Hiroi N., Yamada T., Funahashi A.

Applied Sciences (Switzerland) （Applied Sciences (Switzerland)）  9 （ 24 ）  2019年12月

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

© 2019 by the authors. Regenerative medicine using neural stem cells (NSCs), which self-renew and have pluripotency, has recently attracted a lot of interest. Much research has focused on the transplantation of differentiated NSCs to damaged tissues for the treatment of various neurodegenerative diseases and spinal cord injuries. However, current approaches for distinguishing differentiated from non-differentiated NSCs at the single-cell level have low reproducibility or are invasive to the cells. Here, we developed a fully automated, non-invasive convolutional neural network-based model to determine the differentiation status of human NSCs at the single-cell level from phase-contrast photomicrographs; after training, our model showed an accuracy of identification greater than 94%. To understand how our model distinguished between differentiated and non-differentiated NSCs, we evaluated the informative features it learned for the two cell types and found that it had learned several biologically relevant features related to NSC shape during differentiation. We also used our model to examine the differentiation of NSCs over time; the findings confirmed our model's ability to distinguish between non-differentiated and differentiated NSCs. Thus, our model was able to non-invasively and quantitatively identify differentiated NSCs with high accuracy and reproducibility, and, therefore, could be an ideal means of identifying differentiated NSCs in the clinic.

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XitoSBML: A Modeling Tool for Creating Spatial Systems Biology Markup Language Models From Microscopic Images

Ii K., Mashimo K., Ozeki M., Yamada T., Hiroi N., Funahashi A.

Frontiers in Genetics （Frontiers in Genetics）  10   1027 2019年10月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1664-8021

　概要を見る

© Copyright © 2019 Ii, Mashimo, Ozeki, Yamada, Hiroi and Funahashi. XitoSBML is a software tool designed to create an SBML (Systems Biology Markup Language) Level 3 Version 1 document from microscopic cellular images. It is implemented as an ImageJ plug-in and is designed to create spatial models that reflect the three-dimensional cellular geometry. With XitoSBML, users can perform spatial model simulations based on realistic cellular geometry by using SBML-supported software tools, including simulators such as Virtual Cell and Spatial Simulator. XitoSBML is open-source and is available at https://github.com/spatialsimulator/XitoSBML/. XitoSBML is confirmed to run on most 32/64-bit operating systems: Windows, MacOS, and Linux.

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Activation of cell migration via morphological changes in focal adhesions depends on shear stress in MYCN-amplified neuroblastoma cells

Hiraiwa T., Yamada T., Miki N., Funahashi A., Hiroi N.

Journal of the Royal Society, Interface （Journal of the Royal Society, Interface）  16 （ 152 ） 20180934 2019年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  17425689

　概要を見る

Neuroblastoma is the most common solid tumour of childhood, and it metastasizes to distant organs. However, the mechanism of metastasis, which generally depends on the cell motility of the neuroblastoma, remains unclear. In many solid tumours, it has been reported that shear stress promotes metastasis. Here, we investigated the relationship between shear stress and cell motility in the MYCN-amplified human neuroblastoma cell line IMR32, using a microfluidic device. We confirmed that most of the cells migrated downstream, and cell motility increased dramatically when the cells were exposed to a shear stress of 0.4 Pa, equivalent to that expected in vivo. We observed that the morphological features of focal adhesion were changed under a shear stress of 0.4 Pa. We also investigated the relationship between malignancy and the motility of IMR32 cells under shear stress. Decreasing the expression of MYCN in IMR32 cells via siRNA transfection inhibited cell motility by a shear stress of 0.4 Pa. These results suggest that MYCN-amplified neuroblastoma cells under high shear stress migrate to distant organs due to high cell motility, allowing cell migration to lymphatic vessels and venules.

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ネムリユスリカの培養細胞の乾燥耐性に迫る

舟橋 啓, 黄川田 隆洋

B&I バイオサイエンスとインダストリー （(一般財団法人)バイオインダストリー協会(JBA)）  77 （ 4 ） 310 - 311 2019年

共著

• CiNii Research

画像解析と深層学習を用いた診断の基礎

舟橋 啓

病理と臨床 37   631 - 635 2019年

共著, 査読有り

• CiNii Research

Quantitative analysis of sensitivity to a Wnt3a gradient in determination of the pole-to-pole axis of mitotic cells by using a microfluidic device

Hiraiwa T., Nakai Y., Yamada T., Tanimoto R., Kimura H., Matsumoto Y., Miki N., Hiroi N., Funahashi A.

FEBS Open Bio （FEBS Open Bio）  8 （ 12 ） 1920 - 1935 2018年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  22115463

　概要を見る

© 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. Proper determination of the cell division axis is essential during development. Wnt3a is a known regulator of the cell division axis; however, the sensitivity of cells to Wnt3a signalling and its role in determining the cell division axis have not been measured to date. To address this gap, we took advantage of the asymmetric distribution of outer dense fibre 2 (ODF2/cenexin) proteins on centrosomes in dividing cells. To precisely quantify the sensitivity of cells to Wnt3a signalling, we developed a microfluidic cell culture device, which can produce a quantitative gradient of signalling molecules. We confirmed that mitotic SH-SY5Y neuroblastoma cells could detect a 2.5 ~ 5 × 10−3 nm·μm−1 Wnt3a concentration gradient and demonstrated that this gradient is sufficient to affect the determination of the pole-to-pole axis of cell division during the later stages of mitosis.

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Transcriptome analysis of the anhydrobiotic cell line Pv11 infers the mechanism of desiccation tolerance and recovery

Yamada T., Suetsugu Y., Deviatiiarov R., Gusev O., Cornette R., Nesmelov A., Hiroi N., Kikawada T., Funahashi A.

Scientific Reports （Scientific Reports）  8 （ 1 ） 17941 2018年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2045-2322

　概要を見る

© 2018, The Author(s). The larvae of the African midge, Polypedilum vanderplanki, can enter an ametabolic state called anhydrobiosis to overcome fatal desiccation stress. The Pv11 cell line, derived from P. vanderplanki embryo, shows desiccation tolerance when treated with trehalose before desiccation and resumes proliferation after rehydration. However, the molecular mechanisms of this desiccation tolerance remain unknown. Here, we performed high-throughput CAGE-seq of mRNA and a differentially expressed gene analysis in trehalose-treated, desiccated, and rehydrated Pv11 cells, followed by gene ontology analysis of the identified differentially expressed genes. We detected differentially expressed genes after trehalose treatment involved in various stress responses, detoxification of harmful chemicals, and regulation of oxidoreduction that were upregulated. In the desiccation phase, L-isoaspartyl methyltransferase and heat shock proteins were upregulated and ribosomal proteins were downregulated. Analysis of differentially expressed genes during rehydration supported the notion that homologous recombination, nucleotide excision repair, and non-homologous recombination were involved in the recovery process. This study provides initial insights into the molecular mechanisms underlying the extreme desiccation tolerance of Pv11 cells.

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Convolutional neural network-based instance segmentation algorithm to acquire quantitative criteria of early mouse development

Y Tokuoka, TG Yamada, N Hiroi, TJ Kobayashi, K Yamagata, ...

BioRxiv, 324186 2018年06月

研究論文（学術雑誌）, 共著, 査読有り

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Quantitative analysis of sensitivity to a Wnt3a gradient in determination of the pole‐to‐pole axis of mitotic cells by using a microfluidic device

T Hiraiwa, Y Nakai, TG Yamada, R Tanimoto, H Kimura, Y Matsumoto, ...

FEBS open bio 8 (12), 1920-1935 2018年

研究論文（学術雑誌）, 共著, 査読有り

Requirement of spatiotemporal resolution for imaging intracellular temperature distribution

Hiroi Noriko, Tanimoto Ryuichi, Ii Kaito, Ozeki Mitsunori, Mashimo Kota, Funahashi Akira

BIOMEDICAL IMAGING AND SENSING CONFERENCE 10251 2017年04月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  978-1-5106-1004-0

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Editorial: Quantitative Biology: Dynamics of Living Systems

舟橋 啓

FRONTIERS IN PHYSIOLOGY 7   196 2016年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1664-042X

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システムバイオロジーにおけるシミュレーション技術と実装

舟橋 啓, 広井 賀子

日本薬理学雑誌 （日本薬理学会）  147 （ 2 ） 101 - 106 2016年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0015-5691

　概要を見る

生命現象の理解には個別のコンポーネントについての理解に加え，それらの統合されたふるまいを知る必要がある．このような様々な分子のダイナミクスの背景にあるメカニズムを理解する上で強力なツールとなるのが数理モデルである．システムバイオロジーでは，数理モデルを用いて生命現象を司るメカニズムを理解する手法を頻用する．歴史的には解析的に解くことが可能なモデルが用いられたが，コンピュータの発達により，常微分方程式モデル，偏微分方程式モデル，確率モデル，これらのハイブリッドモデルなど多岐に渡る形式で記述されたモデルを数値計算によって解くようになった．こうした背景から，作成したモデルの正しい挙動を数値的に得るための，正確な数値計算技術が不可欠の要素となっている．本稿では，各モデル化手法の特徴を概説した後，システムバイオロジー研究において広く利用されている代表的なアプリケーション（シミュレータ）について，ソフトウェアの全体像から実装されているアルゴリズムまで，原典を挙げて解説する．数値計算手法の実装内容を正確に知ることは，ユーザにとってはモデルが備えるべき内容を理解し，結果を正しく解釈するために有用となる．また開発者にとっては，不必要な重複を避け，新しいブレークスルーを実現するための技術が何であるか，自らの創造性の発端を得るためにより重要な知識となるだろう．

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3D蛍光顕微鏡画像からの哺乳類着床前胚の発生動態の再構成 (医用画像)

小林 徹也, 尾関 光徳, 山縣 一夫, 舟橋 啓

電子情報通信学会技術研究報告 = IEICE technical report : 信学技報 （一般社団法人電子情報通信学会）  114 （ 482 ） 1 - 6 2015年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0913-5685

　概要を見る

哺乳類着床前胚の発生過程に関する情報を経時的な顕微鏡観察画像から得ることは,近年基礎生物学のみならず生殖補助医療などでも重要な課題となっている.本研究では,細胞の移動・増殖などで形成される細胞系譜の情報をバイオイメージングデータから画像解析を用いて抽出する研究について概説し,整数計画法を用いたマウス着床前胚の発生細胞系譜の追跡についての我々の結果を報告する.

A proteomic study of mitotic phase-specific interactors of EB1 reveals a role for SXIP-mediated protein interactions in anaphase onset

Tamura Naoka, Simon Judith E., Nayak Arnab, Shenoy Rajesh, Hiroi Noriko, Boilot Viviane, Funahashi Akira, Draviam Viji M.

BIOLOGY OPEN 4 （ 2 ） 155 - 169 2015年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2046-6390

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定量的生命科学のためのバイオ画像解析とその哺乳類発生動態への応用

小林 徹也, バシャール カイルル, 舟橋 啓, 藤森 俊彦, 山縣 一夫

Ｍｅｄｉｃａｌ　Ｉｍａｇｉｎｇ　Ｔｅｃｈｎｏｌｏｇｙ （日本医用画像工学会）  33 （ 3 ） 84 - 89 2015年

共著, 査読有り,  ISSN  0288450X

　概要を見る

バイオイメージング技術の発展と普及とともに，顕微鏡イメージから生命システムの動態に関する情報を定量的に取得する方法としてバイオ画像解析技術は大きく注目されている．本稿では，イメージングデータへの画像解析の応用事例について概説するとともに，哺乳類着床前胚の発生動態と細胞系譜の再構成を目的とするわれわれの研究の進展について紹介する．

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増大特集 生命動態システム科学 Ⅰ.定量生物学 1.分子・細胞の計測 1)基本技術 (2)生命現象のシステムレベルでの理解に向けた基盤技術開発

舟橋 啓

生体の科学 （株式会社医学書院）  65 （ 5 ） 388 - 389 2014年10月

共著, 査読有り,  ISSN  03709531

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FABRICATION METHOD TO A HIGH RESOLUTION CONTROL IN THE SPACE OF CELL CULTURING ENVIRONMENT WITH MICROFLUIDIC SYSTEM

Hiraiwa Takumi, Kimura Tadamasa, Takenaka Yuma, Tanamoto Ryo, Ota Hiroki, Kimura Hiroshi, Taguchi Yoshihiro, Miki Norihisa, Matsumoto Yoshinori, Oka Kotaro, Funahashi Akira, Hiroi Noriko

2014 IEEE 27TH INTERNATIONAL CONFERENCE ON MICRO ELECTRO MECHANICAL SYSTEMS (MEMS)    264 - 267 2014年01月

研究論文（国際会議プロシーディングス）, 共著, 査読有り

Modeling and Simulation Using CellDesigner

Matsuoka Yukiko, Funahashi Akira, Ghosh Samik, Kitano Hiroaki

TRANSCRIPTION FACTOR REGULATORY NETWORKS: METHODS AND PROTOCOLS 1164   121 - 145 2014年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1064-3745

　概要を見る

<p>In silico modeling and simulation are effective means to understand how the regulatory systems function in life. In this chapter, we explain how to build a model and run the simulation using CellDesigner, adopting the standards such as SBML and SBGN. </p>

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Assessing uncertainty in model parameters based on sparse and noisy experimental data

Hiroi Noriko, Swat Maciej, Funahashi Akira

FRONTIERS IN PHYSIOLOGY （Frontiers Media SA）  5   128 2014年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1664-042X

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Automated tracking of mitotic spindle pole positions shows that LGN is required for spindle rotation but not orientation maintenance

Corrigan Adam M., Shrestha Roshan L., Zulkipli Ihsan, Hiroi Noriko, Liu Yingjun, Tamura Naoka, Yang Bing, Patel Jessica, Funahashi Akira, Donald Athene, Draviam Viji M.

CELL CYCLE 12 （ 16 ） 2643 - 2655 2013年08月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1538-4101

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in vivo oriented modeling with consideration of intracellular crowding

Hiroi Noriko, Iba Keisuke, Tabira Akito, Okuhara Takahiro, Kubojima Takeshi, Hiraiwa Takumi, Kobayashi Tetsuya J., Oka Kotaro, Funahashi Akira

2013 35TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) 2013   2716 - 2719 2013年07月

研究論文（国際会議プロシーディングス）, 共著, 査読有り,  ISSN  1557-170X

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The systems biology simulation core algorithm

Keller Roland, Doerr Alexander, Tabira Akito, Funahashi Akira, Ziller Michael J., Adams Richard, Rodriguez Nicolas, Le Novere Nicolas, Hiroi Noriko, Planatscher Hannes, Zell Andreas, Draeger Andreas

BMC SYSTEMS BIOLOGY 7   2643 - 2655 2013年07月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1752-0509

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LibSBMLSim: a reference implementation of fully functional SBML simulator

Takizawa Hiromu, Nakamura Kazushige, Tabira Akito, Chikahara Yoichi, Matsui Tatsuhiro, Hiroi Noriko, Funahashi Akira

BIOINFORMATICS 29 （ 11 ） 1474 - 1476 2013年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1367-4803

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Meeting report of the International Workshop on Quantitative Biology 2012: mesoscopic and microscopic worlds meet.

Draviam VM, Funahashi A, Hiroi N, Kimura A, Kobayashi TJ

Frontiers in physiology （Frontiers Media SA）  3   479 2013年01月

研究論文（学術雑誌）, 共著, 査読有り

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Mathematical Modeling of Sustainable Synaptogenesis by Repetitive Stimuli Suggests Signaling Mechanisms In Vivo

瀧沢 大夢, 広井 賀子, 舟橋 啓

PLOS ONE 7 （ 12 ） e51000 2012年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1932-6203

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Software support for SBGN maps: SBGN-ML and LibSBGN

van Iersel Martijn P., Villeger Alice C., Czauderna Tobias, Boyd Sarah E., Bergmann Frank T., Luna Augustin, Demir Emek, Sorokin Anatoly, Dogrusoz Ugur, Matsuoka Yukiko, Funahashi Akira, Aladjem Mirit I., Mi Huaiyu, Moodie Stuart L., Kitano Hiroaki, Le Novere Nicolas, Schreiber Falk

BIOINFORMATICS 28 （ 15 ） 2016 - 2021 2012年08月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1367-4803

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Physiological intracellular crowdedness is defined by the perimeter-to-area ratio of sub-cellular compartments

Hiroi Noriko, Okuhara Takahiro, Kubojima Takeshi, Iba Keisuke, Tabira Akito, Yamashita Shuji, Okada Yasunori, Kobayashi Tetsuya J., Funahashi Akira

FRONTIERS IN PHYSIOLOGY （Frontiers Media SA）  3   293 2012年07月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1664-042X

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From microscopy data to in silico environments for in vivo-oriented simulations.

Hiroi1 N, Klann M, Iba K, Heras Ciechomski Pd, Yamashita S, Tabira A, Okuhara T, Kubojima T, Okada Y, Oka K, Mange R, Unger M, Funahashi A, Koeppl H

EURASIP journal on bioinformatics & systems biology （Springer International Publishing AG）  2012 （ 1 ） 7 2012年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1687-4145

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BioPAX support in CellDesigner

Mi Huaiyu, Muruganujan Anushya, Demir Emek, Matsuoka Yukiko, Funahashi Akira, Kitano Hiroaki, Thomas Paul D.

BIOINFORMATICS 27 （ 24 ） 3437 - 3438 2011年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1367-4803

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Physiological environment induces quick response–slow exhaustion reactions

N Hiroi, J Lu, K Iba, A Tabira, S Yamashita, Y Okada, F Christoph, K Oka, ...

Frontiers in Physiology 2, 50 （Frontiers Media SA）  2   50 2011年09月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1664-042X

　概要を見る

In vivo environments are highly crowded and inhomogeneous, which may affect reaction processes in cells. In this study we examined the effects of intracellular crowding and an inhomogeneity on the behavior of in vivo reactions by calculating the spectral dimension (d(s)), which can be translated into the reaction rate function. We compared estimates of anomaly parameters obtained from fluorescence correlation spectroscopy (FCS) data with fractal dimensions derived from transmission electron microscopy (TEM) image analysis. FCS analysis indicated that the anomalous property was linked to physiological structure. Subsequent TEM analysis provided an in vivo illustration; soluble molecules likely percolate between intracellular clusters, which are constructed in a self-organizing manner. We estimated a cytoplasmic spectral dimension d(s) to be 1.39 +/- 0.084. This result suggests that in vivo reactions initially run faster than the same reactions in a homogeneous space; this conclusion is consistent with the anomalous character indicated by FCS analysis. We further showed that these results were compatible with our Monte-Carlo simulation in which the anomalous behavior of mobile molecules correlates with the intracellular environment, leading to description as a percolation cluster, as demonstrated using TEM analysis. We confirmed by the simulation that the above-mentioned in vivo like properties are different from those of homogeneously concentrated environments. Additionally, simulation results indicated that crowding level of an environment might affect diffusion rate of reactant. Such knowledge of the spatial information enables us to construct realistic models for in vivo diffusion and reaction systems.

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The DBCLS BioHackathon: standardization and interoperability for bioinformatics web services and workflows

T Katayama, K Arakawa, M Nakao, K Ono, KF Aoki-Kinoshita, ...

Journal of biomedical semantics 1 (1), 8 （BioMed Central）  1 （ 1 ） 1 - 19 2010年12月

研究論文（学術雑誌）, 共著, 査読有り

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A datapath classification method for FPGA-based scientific application accelerator systems

Y Ogawa, T Ooya, Y Osana, M Yoshimi, Y Nishikawa, A Funahashi, ...

2010 International Conference on Field-Programmable Technology, 441-444 （IEEE）     441 - 444 2010年12月

研究論文（国際会議プロシーディングス）, 共著, 査読有り

　概要を見る

Resource reduction design techniques play an important role to implement large-scale FPGA-based accelerator systems in floating point applications since available resources on FPGAs are limited. This paper proposes a dataflow graph classification method which makes groups of graphs based on their similarity in order to bring out efficient graph combining. Aiming at finding effective parameters for the k-means algorithm, various parameter combinations are evaluated and compared in terms of resource reduction effects and performance. The experimental results using an FPGA-based biochemical simulator reveal that the graph clustering that uses information on the maximum common subgraphs achieve 73.3% of resource reduction rate while alleviating the performance degradation. © 2010 IEEE.

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細胞シミュレータCellDesignerの設計と実装

舟橋 啓, 松岡 由希子, 上樂 明也, 瀧沢 大夢, 広井 賀子, Samik Ghosh, 菊池 紀広, 北野 宏明

計測と制御 （公益社団法人 計測自動制御学会）  49 （ 8 ） 531 - 536 2010年08月

共著, 査読有り,  ISSN  04534662

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Automatic Pipeline Construction Focused on Similarity of Rate Law Functions for an FPGA-based Biochemical Simulator

Hideki Yamada, Yui Ogawa, Tomonori Ooya, Tomoya Ishimori, Yasunori Osana, Masato Yoshimi, Yuri Nishikawa, Akira Funahashi, Noriko Hiroi, Hideharu Amano, Yuichiro Shibata, Kiyoshi Oguri

IPSJ Transactions on System LSI Design Methodology （一般社団法人情報処理学会）  3 （ 3 ） 244 - 256 2010年08月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1882-6687

　概要を見る

For FPGA-based scientific simulation systems, hardware design technique that can reduce required amount of hardware resources is a key issue, since the size of simulation target is often limited by the size of the FPGA. Focusing on FPGA-based biochemical simulation, this paper proposes hardware design methodology which finds and combines common datapath for similar rate law functions appeared in simulation target models, so as to generate area-effective pipelined hardware modules. In addition, similarity-based clustering techniques of rate law functions are also presented in order to alleviate negative effects on performance for combined pipelines. Empirical evaluation with a practical biochemical model reveals that our method enables the simulation with 66% of the original hardware resources at a reasonable cost of 20% performance overhead.

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A Modular Approach to Heterogeneous Biochemical Model Simulation on an FPGA

Yamada Hideki, Osana Yasunori, Ishimori Tomoya, Ooya Tomonori, Yoshimi Masato, Nishikawa Yuri, Funahashi Akira, Hiroi Noriko, Amano Hideharu, Shibata Yuichiro, Oguri Kiyoshi

2009 INTERNATIONAL CONFERENCE ON RECONFIGURABLE COMPUTING AND FPGAS （IEEE）     125 - 130 2009年12月

研究論文（国際会議プロシーディングス）, 共著, 査読有り,  ISSN  978-1-4244-5293-4

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CONFIGURING AREA AND PERFORMANCE: EMPIRICAL EVALUATION ON AN FPGA-BASED BIOCHEMICAL SIMULATOR

Ooya T., Yamada H., Ishimori T., Shibata Y., Osana Y., Oguri K., Yoshimi M., Nishikawa Y., Funahashi A., Hiroi N., Amano H.

FPL: 2009 INTERNATIONAL CONFERENCE ON FIELD PROGRAMMABLE LOGIC AND APPLICATIONS （IEEE）     679 - 682 2009年08月

研究論文（国際会議プロシーディングス）, 共著, 査読有り,  ISSN  1946-1488

　概要を見る

One of the obvious advantages of FPGA-based reconfigurable computing is customizability of a tradeoff point between performance and hardware costs. However, this tradeoff has rarely been discussed in a whole application level, which is the most important view for application users. This paper presents empirical evaluation of a hardware module sharing technique which can shift a tradeoff point of area and performance on an FPGA-based biochemical simulator. The biochemical simulation results are discussed in terms of hardware costs, simulation throughput, parallelism extracted in simulation hardware, and data transfer overheads.

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FPGAを用いた生化学シミュレータにおける入力ポート制約を考慮した演算パイプラインスケジューリング

石森 智也, 山田 英樹, 柴田 裕一郎, 長名 保範, 吉見 真聡, 西川 由理, 小嶋 利紀, 天野 英晴, 舟橋 啓, 広井 賀子, 小栗 清

電子情報通信学会技術研究報告. RECONF, リコンフィギャラブルシステム : IEICE technical report （一般社団法人電子情報通信学会）  5453 （ 2009 ） 368 - 373 2009年03月

研究論文（国際会議プロシーディングス）, 共著, 査読有り,  ISSN  978-3-642-00640-1

　概要を見る

FPGAベースの生化学シミュレータでは,デバイスの資源制約を考慮した高スループットな回路設計が重要である.本稿では,データの入力ポートの制約とハードウェアコストの削減を考慮した演算パイプラインスケジューリング手法を提案する.入力データの優先付けを工夫して,優先順位にしたがって投入タイミングを決定することで,スケジューリングへの影響を小さくする方法を提案する.評価の結果,ALAPスケジューリングと比較して平均7.6%のハードウェア量を削減することができた.

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3P-239 分子クラウディング効果が細胞内化学反応に及ぼす影響(数理生物学,第47回日本生物物理学会年会)

K Yashima, N Hiroi, A Funahashi, K Oka

生物物理 （一般社団法人 日本生物物理学会）  49 （ supplement ） S191 2009年

共著, 査読有り,  ISSN  05824052

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FPGAを用いた高スループット確率モデル生化学シミュレータの設計と評価

吉見 真聡、西川 由理、長名 保範、舟橋 啓、広井 賀子、柴田 裕一郎、山田 英樹、北野 宏明、天野 英晴

情報処理学会論文誌: コンピュータシステム （情報処理学会）  1 （ 3 ） 120-135 - 135 2008年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1882-7829

　概要を見る

確率モデル生化学シミュレーションアルゴリズム（SSA）は，生化学モデルの確率的挙動を厳密に計算できる手法として知られている．しかしその一方で，SSAを用いてモデルを評価するためには，膨大な回数の演算が繰り返されるので，高スループットな実行環境が求められている．本論文では，FPGAを用いて計算効率の良いSSAであるNext Reaction Method（NRM）を高スループットに実行するハードウェアの構造について述べ，性能評価を行う．このハードウェアは，シミュレーションスレッドの状態を保持するスレッドモジュールが，データ転送網を介して算術演算器やデータメモリを共有する構造を持ち，マルチスレッド実行を行う．また，モジュール間の接続を変更することで，特定のFPGAに限定されない構成の変更が可能である．ミドルレンジのFPGA上に構成することを想定して16スレッドの並列実行を行うハードウェアを実装し，評価用によく利用されるHSRモデルによるRTLシミュレーションを通してスループットを計測した結果，Core 2 Quad Q6600 2.40 GHzのシングルスレッド実行と比べて約4.2倍，HSRを並べて作成した反応数の多い仮想のモデルでは約5.4倍のスループットの向上が可能であることを確認した．Stochastic biochemical simulation algorithms (SSAs) are generally known as exact methods to trace stochastic behaviors of target biochemical models. Due to vast amount of computation attributed to the nature of Monte Carlo Method, which SSAs are originated from, there is a strong urge for high-throughput execution environment. This paper proposes an FPGA implementation of a stochastic simulation system based on a computationally-efficient SSA called the Next Reaction Method, and studies the evaluation results of area and throughput in detail. The system conducts high-throughput multi-thread execution, using multiple thread modules accessing shared arithmetic and data modules. The network between modules are configurable, and supports flexible network structure according to target FPGAs. In order to evaluate the proposed design, the stochastic simulation system, which is capable of running 16 threads in parallel, was implemented on a middle-range FPGA. As the result of comparing the throughput in RTL simulation with software simulation run on Core 2 Quad Q6600, the system marked 4.2 times higher throughput using a real biochemical model called HSR. When several versions of virtually largescale models were tested on the same simulation environment, maximum of 5.4 times higher throughput was confirmed.

PRACTICAL IMPLEMENTATION OF A NETWORK-BASED STOCHASTIC BIOCHEMICAL SIMULATION SYSTEM ON AN FPGA

Yoshimi Masato, Nishikawa Yuri, Osana Yasunori, Funahashi Akira, Hiroi Noriko, Shibata Yuichiro, Yamada Hideki, Kitano Hiroaki, Amano Hideharu

2008 INTERNATIONAL CONFERENCE ON FIELD PROGRAMMABLE AND LOGIC APPLICATIONS, VOLS 1 AND 2 （IEEE）     663 - 666 2008年09月

研究論文（国際会議プロシーディングス）, 共著, 査読有り,  ISSN  978-1-4244-1960-9

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FPGA上でのシミュレーションに向けた生化学コンパイラの実装

岩岡 洋, 長名 保範, 吉見 真聡, 西川 由理, 小嶋 利紀, 舟橋 啓, 広井 賀子, 柴田 裕一郎, 岩永 直樹, 北野 宏明, 天野 英晴

電子情報通信学会論文誌 D J91-D （ 9 ） 2205-2216 2008年09月

研究論文（学術雑誌）, 単著, 査読有り

CellDesigner 3.5: A versatile modeling tool for biochemical networks

舟橋 啓, 松岡 由季子, 上樂 明也, 諸橋 峰雄, 菊池 紀広, 北野 宏明

PROCEEDINGS OF THE IEEE 96 （ 8 ） 1254-1265 - 1265 2008年08月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0018-9219

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A framework for implementing a network-based stochastic biochemical simula tor on an FPGA

Yoshimi Masato, Nishikawa Yuri, Kojima Toshinori, Osana Yasunori, Funahashi Akira, Hiroi Noriko, Shibata Yuichiro, Yamada Hideki, Kitano Hiroaki, Amano Hideharu

ICFPT 2007: INTERNATIONAL CONFERENCE ON FIELD-PROGRAMMABLE TECHNOLOGY, PROCEEDINGS （IEEE）     193 - 200 2007年12月

研究論文（国際会議プロシーディングス）, 共著, 査読有り,  ISSN  978-1-4244-1471-0

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Deduction of intracellular sub-systems from a topological description of the network.

NORDLING Torbjorn, HIROI, Noriko, FUNAHASHI Akira and KITANO Hiroaki

Molecular Biosystems 3 （ 8 ） 523-529 2007年08月

研究論文（学術雑誌）, 共著, 査読有り

A combining technique of rate law functions for a cost-effective reconfigurable biological simulator

H Yamada, N Iwanaga, Y Shibata, Y Osana, M Yoshimi, Y Iwaoka, ...

2007 International Conference on Field Programmable Logic and Applications … （IEEE）     808 - 811 2007年08月

研究論文（国際会議プロシーディングス）, 共著, 査読有り,  ISSN  1946-1488

　概要を見る

In order to simulate large scale biological models with a reconfigurable FPGA-based biochemical simulator system, reduction of required resources are essential. This paper proposes a method which combines common terms in rate law functions appeared in biochemical models and generates a shared hardware module used for numerical integration. In this approach, two functions are combined in a tree structure level, followed by pipeline scheduling and arithmetic module binding. The evaluation result reveals that this approach reduces hardware resources by 31.4 % on average at the cost of 14.4 % throughput degradation.

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FPGA implementation of a data-driven stochastic biochemical simulator with the next reaction method

Yoshimi Masato, Iwaoka Yow, Nishikawa Yuri, Kojima Toshinori, Osana Yastmori, Funahashi Akira, Hiroi Noriko, Shibata Yuichiro, Iwanaga Naoki, Kitano Hiroaki, Amano Hideharu

2007 INTERNATIONAL CONFERENCE ON FIELD PROGRAMMABLE LOGIC AND APPLICATIONS, PROCEEDINGS, VOLS 1 AND 2 （IEEE）     254 - 259 2007年08月

研究論文（国際会議プロシーディングス）, 共著, 査読有り,  ISSN  978-1-4244-1059-0

ReCSiP: An FPGA-Based Biochemical Simulator

Osana, Y., Yoshimi, M., Iwaoka, Y., Kojima, T., Nishikawa, Y., Funahashi, A., Hiroi, N., Shibata, Y., Iwanaga, N., Kitano, H., and Amano, H

Electronics and Communications in Japan (Part II: Electronics) 90 （ 7 ） 1-10 2007年07月

研究論文（学術雑誌）, 共著, 査読有り

An integration of CellDesigner and SABIO-RK

FUNAHASHI Akira, JOURAKU Akiya, MATSUOKA Yukiko, KITANO Hiroaki

In Silico Biology 7 （ 2 ） S81-S90. 2007年03月

研究論文（学術雑誌）, 共著, 査読有り

FPGAを用いた確率モデル生化学シミュレータ.

吉見 真聡, 長名 保範, 岩岡 洋, 西川 由理, 小嶋 利紀, 柴田 裕一郎, 岩永 直樹, 舟橋 啓, 広井 賀子, 北野 宏明, and 天野 英晴

情報処理学会論文誌 コンピューティングシステム （一般社団法人情報処理学会）  48 （ SIG 3 (ACS 17) ） 45-58 - 58 2007年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1882-7829

　概要を見る

確率モデル生化学シミュレーションアルゴリズム（SSA）は，定義した生化学システムの確率的挙動を厳密に計算できるアルゴリズムとして知られている．しかし，SSA の実行には膨大な計算時間が必要であり，高速な実行環境が求められている．本論文では，高速実行の一手法として，Xilinx 社のFPGA（XC2VP70-5）を用いて，SSA（First Reaction Method）を実行する回路を実装，評価した結果について述べる．高速化は，パイプライン化した演算ユニットを使い，複数スレッドのシミュレーションを同時に実行することで実現する．シミュレータ回路は，中間データをBlockRAM に保持し対象の生化学システムごとの回路再構成を要しない，実用的な構造になっている．ベンチマーク的に定義できる生化学システムTIS，D4S で評価した結果，Xeon 2.80 GHz による実行と比較して，TIS では約83 倍，D4S では約95 倍のスループット向上が可能であることを確認した．This paper discusses an FPGA implementation and evaluation of a Stochastic Simulation Algorithm (SSA) called the First Reaction Method. SSAs are widely known as rigorous methods for simulating the stochastic behaviors of various biochemical systems, but also as CPU-hogging applications due to vast repetition of the algorithm. This work accelerates the execution by achieving high throughput with concurrent simulations of highly utilized pipelined arithmetic units. For upgrading practical utility, the design stores intermediate data in a BlockRAM so that reconfiguration is unnecessary for different target biochemical systems. Benchmark results on an FPGA (Xilinx XC2VP70-5) have shown that the circuit provides throughput of approximately 83 times and 95 times compared to software execution on Xeon 2.80 GHz when it was evaluated with biochemical models called TIS and D4S, respectively.

CellDesigner

Funahashi Akira, Morohashi Mineo, Matsuoka Yukiko, Jouraku Akiya, Kitano Hiroaki

  422 - 434 2007年

　概要を見る

<p>Understanding the logic and dynamics of gene-regulatory and biochemical networks is a major challenge of systems biology. To facilitate this research topic, we have developed CellDesigner, a modeling tool of gene-regulatory and biochemical networks. CellDesigner supports users to easily create such networks, using solidly defined and comprehensive graphical representation (SBGN, systems biology graphical notation). CellDesigner is systems biology markup language (SBML) compliant, and has Systems Biology Workbench(SBW)-enabled software so that it can import/export SBML-described documents and integrate with other SBW-enabled simulation/analysis software packages. CellDesigner also supports simulation and parameter search, which is supported by integration with SBML ordinary differential equation (ODE) Solver, enabling us to simulate through our sophisticated graphical user interface. We can also browse and modify existing SBML models with references to existing databases. CellDesigner is implemented in Java; thus, it runs on various platforms such as Windows, Linux, and MacOS X. CellDesigner is freely available from our Web site at http://celldesigner.org/. © 2007 Humana Press Inc.</p>

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Integration of CellDesigner and SABIO-RK.

Funahashi A, Jouraku A, Matsuoka Y, Kitano H

In silico biology 7 （ SUPPL. 2 ） 81 - 90 2007年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1386-6338

　概要を見る

<p>Understanding the logic and dynamics of gene-regulatory and biochemical networks is a major challenge for systems biology. To facilitate this research topic, we have developed CellDesigner to visualize, model and simulate biochemical networks. CellDesigner allows the users to easily create networks using solidly defined and comprehensive graphical notation. CellDesigner utilizes SBML to described models and can simulate models using an integrated SBML ODE Solver or third party simulation engine; thus enabling users to simulate through a sophisticated graphical user interface. Although CellDesigner can integrate with existing databases (KEGG, PubMed, BioModels, etc.), by calling a web browser, or connecting to its web page through HTTP, integration with SABIO-RK has the potential to expand connectivity and semi-automate visualization and model building. SABIO-RK contains information about biochemical reactions, related kinetic equations and parameters. Also information about the experimental conditions under which these parameters were measured is stored. By using the Web service API provided by the SABIO-RK team, we have succeeded to directly connect to the database, send search queries by ID or name of its component, and then import the query results into CellDesigner. © 2007 IOS Press. All rights reserved.</p>

SBML models and MathSBML

Shapiro Bruce E., Finney Andrew, Hucka Michael, Bornstein Benjamin, Funahashi Akira, Jouraku Akiya, Keating Sarah M., Le Novère Nicolas, Matthews Joanne, Schilstra Maria J.

  395 - 421 2007年

　概要を見る

<p>MathSBML is an open-source, freely downloadable Mathematica package that facilitates working with Systems Biology Markup Language (SBML) models. SBML is a tool-neutral, computer-readable format for representing models of biochemical reaction networks, and it is applicable to metabolic networks, cell signaling pathways, genomic regulatory networks, and other modeling problems in systems biology that is widely supported by the systems biology community. SBML is based on XML, which is a standard medium for representing and transporting data that is widely supported on the Internet, as well as in computational biology and bioinformatics. Because SBML is tool-independent, it enables model transportability, reuse, publication, and survival. In addition to Math- SBML, a number of other tools that support SBML model examination and manipulation are provided on the http://sbml.org Web site, including libSBML, which is a C/C++ library for reading SBML models; an SBML Toolbox for MATLAB; file conversion programs; an SBML model validator and visualizer; and SBML specifications and schemas. MathSBML enables SBML file import to and export from Mathematica, as well as providing an API for model manipulation and simulation. © 2007 Humana Press Inc.</p>

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Kinetics of dimension-restricted conditions

N Hiroi, A Funahashi

Introduction to Systems Biology, 261-281    261 - 281 2007年

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

<p>The intracellular environment is crowded with skeletal proteins, organelle membranes, ribosomes, and so on. When molecular movement is restricted by such environments, some biochemical reaction processes cannot be represented by classical models, which assume that reactions occur in simple Newtonian fluids. Dimension-restricted reaction kinetics (DRRK) modeling is a method that can represent dimension-restricted reactions. We introduce the methods of DRRK in each case of reaction type. DRRK has another advantage in that it can be quantitatively evaluated by biochemical experiments. We also introduce the procedure of applying it for experimental results. This modeling method may provide the basis for in vivo-oriented modeling. © 2007 Humana Press Inc.</p>

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Deduction of intracellular sub-systems from a topological description of the network

Nordling Torbjörn E M, Hiroi Noriko, Funahashi Akira, Kitano Hiroaki

Molecular BioSystems 3 （ 8 ） 523 - 529 2007年

ISSN  1742-206X

　概要を見る

<p>Non-linear behaviour of biochemical networks, such as intracellular gene, protein or metabolic networks, is commonly represented using graphs of the underlying topology. Nodes represent abundance of molecules and edges interactions between pairs of molecules. These graphs are linear and thus based on an implicit linearization of the kinetic reactions in one or several dynamic modes of the total system. It is common to use data from different sources - experiments conducted under different conditions or even on different species - meaning that the graph will be a superposition of linearizations made in many different modes. The mixing of different modes makes it hard to identify functional modules, that is sub-systems that carry out a specific biological function, since the graph will contain many interactions that do not naturally occur at the same time. The ability to establish a boundary between the sub-system and its environment is critical in the definition of a module, contrary to a motif in which only internal interactions count. Identification of functional modules should therefore be done on graphs depicting the mode in which their function is carried out, i.e. graphs that only contain edges representing interactions active in the specific mode. In general, when an interaction between two molecules is established, one should always state the mode of the system in which it is active. This journal is © The Royal Society of Chemistry.</p>

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Introduction to systems biology

S Choi

Humana press 2007年

研究論文（学術雑誌）, 共著, 査読有り

CellDesigner: a modeling tool for biochemical networks

Akira Funahashi, Yukiko Matsuoka, Akiya Jouraku, Hiroaki Kitano, Norihiro Kikuchi

Proceedings of the 38th conference on Winter simulation conference (WSC'06) （Winter Simulation Conference）     1707 - 1712 2006年12月

研究論文（国際会議プロシーディングス）, 共著, 査読有り

Performance evaluation of an FPGA-based biochemical simulator ReCSiP

Osana Yasunori, Yoshimi Masato, Iwaoka Yow, Kojima Toshinori, Nishikawa Yuri, Funahashi Akira, Hiroi Noriko, Shibata Yuichiro, Iwanaga Naoki, Kitano Hiroaki, Amano Hideharu

2006 INTERNATIONAL CONFERENCE ON FIELD PROGRAMMABLE LOGIC AND APPLICATIONS, PROCEEDINGS （IEEE）     1 - 6 2006年08月

研究論文（国際会議プロシーディングス）, 共著, 査読有り,  ISSN  978-1-4244-0312-7

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An FPGA implementation of high throughput stochastic simulator for large-scale biochemical systems

Yoshimi Masato, Osana Yasunori, Iwaoka Yow, Nishikawa Yuri, Kojima Toshinori, Funahashi Akira, Hiroi Noriko, Shibata Yuichiro, Iwanaga Naoki, Kitano Hiroaki, Amano Hideharu

2006 INTERNATIONAL CONFERENCE ON FIELD PROGRAMMABLE LOGIC AND APPLICATIONS, PROCEEDINGS （IEEE）     1 - 6 2006年08月

研究論文（国際会議プロシーディングス）, 共著, 査読有り,  ISSN  978-1-4244-0312-7

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FPGAを用いた汎用生化学シミュレータReCSiP

長名 保範, 吉見 真聡, 岩岡 洋, 小嶋 利紀, 西川 由理, 舟橋 啓, 広井 賀子, 柴田 裕一郎, 岩永 直樹, 北野 宏明, 天野 英晴

電子情報通信学会論文誌. D, 情報・システム = The IEICE transactions on information and systems (Japanese edition) （一般社団法人電子情報通信学会）  89 （ 6 ） 1163 - 1172 2006年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  18804535

　概要を見る

細胞内部の生化学反応を数理モデルとして記述し,シミュレーションを行うことで生命現象をシステムとして理解しようとする試みが盛んになっている.しかしながら,汎用のマイクロプロセッサで得られる処理能力は決して十分とはいえず,シミュレーションを高速に実行できる計算基盤が求められている.本論文では,FPGAを用いて常微分方程式を用いた生化学モデルのシミュレーションを高速に実行するシステムであるReCSiPの構成とハードウェアの実装について述べる.評価の結果,最大スループットはXilinx社のFPGAであるXC2VP70-5を用いて,Intel Pentium4 3.2GHzの50〜80倍のスループットを達成することができた.

FPGAを用いた汎用生化学シミュレータReCSiP.

長名 保範, 吉見 真聡, 岩岡 洋, 小嶋 利紀, 西川 由理, 舟橋 啓, 広井 賀子, 柴田 裕一郎, 岩永 直樹, 北野 宏明, and 天野 英晴

電子情報通信学会論文誌D J89-D （ 6 ） 1163-1172 - 10 2006年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  8756-663X

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Comparative studies of suppression of malignant cancer cell phenotype by antisense oligo DNA and small interfering RNA

Hiroi N, Funahashi A, Kitano H

CANCER GENE THERAPY （Nature Publishing Group）  13 （ 1 ） 7-12 - 12 2006年01月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0929-1903

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Analysis for Dimension-Restricted Kinetics with Bacterial Endonuclease Movement.

Hiroi, N, Funahashi, A, Kitano, H

WSEAS Transactions on Biology and Biomedicine 3 （ 1 ） 1-6 2006年01月

研究論文（学術雑誌）, 共著, 査読有り

The design of scalable stochastic biochemical simulator on FPGA

Yoshimi M, Osana Y, Iwaoka Y, Funahashi A, Hiroi N, Shibata Y, Iwanaga N, Kitano H, Amano H

FPT 05: 2005 IEEE INTERNATIONAL CONFERENCE ON FIELD PROGRAMMABLE TECHNOLOGY, PROCEEDINGS （IEEE）     339 - 340 2005年12月

研究論文（国際会議プロシーディングス）, 共著, 査読有り,  ISSN  0-7803-9407-0

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Efficient scheduling of rate law functions for ODE-based multimodel biochemical simulation on an FPGA

N Iwanaga, Y Shibata, M Yoshimi, Y Osana, Y Iwaoka, T Fukushima, ...

International Conference on Field Programmable Logic and Applications, 2005 … （IEEE）  2005   666 - 669 2005年08月

研究論文（国際会議プロシーディングス）, 共著, 査読有り

　概要を見る

A reconfigurable biochemical simulator by solving ordinary differential equations has received attention as a personal high speed environment for biochemical researchers. For efficient use of the reconfigurable hardware, static scheduling of high-throughput arithmetic pipeline structures is essential. This paper shows and compares some scheduling alternatives, and analyzes the tradeoffs between performance and hardware amount. Through the evaluation, it is shown that the sharing first scheduling reduces the hardware cost by 33.8% in average, with the up to 11.5% throughput degradation. Effects of sharing of rate law functions are also analyzed. © 2005 IEEE.

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A framework for ODE-based multimodel biochemical simulations on an FPGAs

Y Osana, T Fukushima, M Yoshimi, Y Iwaoka, H Amano, A Funahashi, ...

International Conference on Field Programmable Logic and Applications, 2005 … （IEEE）  2005   574 - 577 2005年08月

研究論文（国際会議プロシーディングス）, 共著, 査読有り

　概要を見る

Today, mathematical modeling and simulation of biochemical pathways take a major role in biological researches. However, modern microprocessors cannot provide enough throughput to explore the large parameter space of target pathways. To address this problem, ReCSiP (a ReConfigurable Cell Simulation Platform), an FPGA-based biochemical simulator is proposed. It's an ODE-based simulator, which solves the rate-law functions. The framework proposed in this paper, enables to simulate pathways consisting many different types of chemical reactions by connecting the rate-law modules (solvers) on an FPGA. It provides the solver-to-solver communication mechanism on an FPGA and automatic configuration software to generate the circuit. © 2005 IEEE.

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An FPGA-based, multi-model simulation method for biochemical systems

Y Osana, T Fukushima, M Yoshimi, Y Iwaoka, A Funahashi, N Hiroi, ...

19th IEEE International Parallel and Distributed Processing Symposium, 4 pp. （IEEE）  2005   4 2005年04月

研究論文（国際会議プロシーディングス）, 共著, 査読有り

　概要を見る

Modeling and simulation of a cellular system on computers are now becoming an essential process in biological researches. However, modern PCs can't provide enough performance to simulate large-scale biochemical networks. ReCSiP is the alternative FPGA-based solution for biochemical simulations. In this paper, the novel method of biochemical simulation with multiple reaction models on an FPGA is proposed. The method generates optimal circuit and its optimal schedule for each simulation models written in SBML, the standard markup language in systems biology. ReCSiP has a Xilinx's XC2VP70 and achieved over 20-fold speedup compared to Intel's PentiumIII 1.13GHz.

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An I/O mechanism on a dynamically reconfigurable processor-which should be moved: data or configuration?

H Amano, S Abe, K Deguchi, Y Hasegawa

International Conference on Field Programmable Logic and Applications, 2005 … 2005   347 - 352 2005年

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

In some applications on Dynamically Reconfigurable Processor (DRP), the input/output of data stream occupies about 20% of total execution time. In order to hide the overhead of input/output, the separation of the I/O context and double-buffering mechanism are proposed. Using the mechanism, I/O overhead of six streaming processing programs can be completely hidden. Based on the analysis of I/O performance, two alternatives for executing parallel processing with multiple DRP Cores are compared and discussed. © 2005 IEEE.

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Evolving a lingua franca and associated software infrastructure for computational systems biology: the Systems Biology Markup Language (SBML) project

M Hucka, A Finney, BJ Bornstein, SM Keating, BE Shapiro, J Matthews, ...

Systems biology 1 (1), 41-53 1 （ 1 ） 41-53 - 53 2004年09月

研究論文（学術雑誌）, 共著, 査読有り

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Molecular Interaction Map of Macrophage.

Oda, K, Kimura, T, Matsuoka, Y, Funahashi, A, Muramatsu, M, Kitano, H

AfCS Report 2 （ 14 ） 1-12 2004年08月

研究論文（学術雑誌）, 共著

Molecular interaction map of a macrophage

K Oda, T Kimura, Y Matsuoka, A Funahashi, M Muramatsu, H Kitano

AfCS Research Reports 2 (14), 1-12 2004年

研究論文（学術雑誌）, 共著, 査読有り

CellDesigner: a process diagram editor for gene-regulatory and biochemical networks

A Funahashi, M Morohashi, H Kitano, N Tanimura

Biosilico 1 (5), 159-162 1 （ 5 ） 159-162 2003年11月

研究論文（学術雑誌）, 共著

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[The ERATO Systems Biology Workbench and Systems Biology Markup Language: an integrated environment and standardization for systems biology].

Funahashi A

Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme 48 （ 7 ） 810 - 6 2003年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0039-9450

The ERATO Systems Biology Workbench and Systems Biology Markup Language

Funahashi Akira

Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme 48 （ 7 ） 810 - 816 2003年

ISSN  0039-9450

Z-routing: イレギュラーネットワークにおける適応型ルーティングに関する研究.

井川 郁哉 and 舟橋 啓

情報処理学会論文誌 43 （ 3 ） 754-763 2002年03月

研究論文（学術雑誌）, 共著, 査読有り

チャネルの使用条件に基づいたアウトプットセレクションファンクションに関する研究.

杉山 伸悟 and 舟橋 啓

情報処理学会論文誌 43 （ 3 ） 764-775 2002年03月

研究論文（学術雑誌）, 共著, 査読有り

Routing algorithms based on 2D turn model for irregular networks

Jouraku, A; Koibuchi, M; Amano, H; Funahashi, A

I-SPAN'02: INTERNATIONAL SYMPOSIUM ON PARALLEL ARCHITECTURES, ALGORITHMS AND NETWORKS, PROCEEDINGS    289 - 294 2002年

共著, 査読有り

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The Impact of Output Selection Function on Adaptive Routing.

Funahashi, A., Koibuchi, M., Jouraku, A., and Amano, H.

ISCA Information: An International Journal 4 （ 4 ） 541-550 2001年11月

研究論文（学術雑誌）, 共著, 査読有り

L-turn routing: Irregular Network における Adaptive Routing.

鯉渕 道紘, 舟橋 啓, 上樂 明也, and 天野 英晴

情報処理学会論文誌ハイパフォーマンスコンピューティングシステム （一般社団法人情報処理学会）  42 （ SIG9 ） 119-134 - 134 2001年08月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0-7695-1257-7

　概要を見る

近年, Personal computerを高速なネットワークで結び, 並列処理を行う研究がさかんに行われている.通常ネットワークはwiring flexibility, scalabilityの要求からトポロジに制限のないirregular networkが用いられるが, 既存のirregular networkのルーティングアルゴリズムは, チャネル使用制限が厳しく, リンクを有効に使うことができない.そこで本稿では各リンクを効果的に使うことを念頭においたadaptive routingであるLeft-up-first turn routing(L-turn routing)を提案する.L-turn routingはirregular networkをdirected-graphに見立てる際に工夫を施すことにより, デッドロックを防ぐために課すパケットの転送禁止ターンの分散を実現する点が特徴であり, 高いトラフィック分散能力を持つ.シミュレーション結果より, L-turn routingは様々なトポロジにおいて高い性能を示すことが分かった.

Recursive Diagonal Torus: An interconnection network for massively parallel computers

Yang YL, Funahashi A, Jouraku A, Nishi H, Amano H, Sueyoshi T

IEEE TRANSACTIONS ON PARALLEL AND DISTRIBUTED SYSTEMS 12 （ 7 ） 701-715 - 715 2001年07月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1045-9219

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適応型ルーティングにおける output selection function に関する研究.

鯉渕 道紘, 舟橋 啓, 上樂 明也, and 天野 英晴

情報処理学会論文誌 42 （ 4 ） 704-713 2001年04月

研究論文（学術雑誌）, 共著, 査読有り

相互結合網 RDT における adaptive routing.

舟橋 啓, 上樂 明也, and 天野 英晴

電子情報通信学会論文誌 （一般社団法人電子情報通信学会）  J89-D-I （ 11 ） 1143-1153 - 1153 2000年11月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  09151915

　概要を見る

相互結合網RDTは再帰構造をもつTorusの重なりから構成されており, 超並列計算機のプロセッサ間接続を行うために優れた性質を多くもっている.超並列計算機に用いられる相互結合網において, 混雑若しくは故障したノードを回避できるルーチングアルゴリズムは必要不可欠である.既存のベクトルルーチングはシンプルではあるが, 固定ルーチング(deterministic routing)であるためこのようなノードを迂回することはできない.本研究では, Duatoによる必要十分条件を用いることによりRDT(2, 4, 1)/α上でデッドロックフリーなadaptive routing algorithim D-RDTとFD-RDTを提案し, デッドロックフリーであることを証明し, 評価を行った.D-RDTは各ランク内のトーラスではfully adaptive routingを行うが, e-cube routingをベースにしているため使用するランク順が固定される.FD-RDTは自由にランクを使用することが可能なバーチャルチャネルを付加したことにより, D-RDTに比べルーチングの自由度は高い.シミュレーションによる評価の結果, 両アリゴリズムとも既存のdeterministic routingに比べ通過率, レイテンシともに性能向上が見られ, 特にFD-RDTを用いたルーチングでは顕著であった.

Torus assignment for an interconnection network recursive diagonal torus

Fan, Qin and Yang, Yulu and Funahashi, Akira and Amano, Hideharu

Proceedings of the International Symposium on Parallel Architectures, Algorithms and Networks, I-SPAN    74 - 79 1999年

共著, 査読有り,  ISSN  1087-4089

　概要を見る

<p>Recursive Diagonal Torus (RDT) is a class of interconnection network consisting of recursively overlaid two-dimensional square diagonal tori for massively parallel computers with up to 2¹⁶ nodes. Connection structures of the RDT vary according to the assignment of upper rank diagonal tori into a node. Although traditional simple assignment called RDT(2, 4, 1)/α shows enough performance under the uniform traffic, the congestion of low rank tori degrades the performance when local communication is dominant. In this paper, RDT(2, 4, 1)/β torus assignment is proposed, focusing on improving the performance for local communication. With a simplified simulation algorithm, results shows that RDT(2, 4, 1)/β improves the average distance compared with RDT(2, 4, 1)/α assignment when considering local area.</p>

A torus assignment for an interconnection network recursive diagonal torus

Q Fan, Y Yang, A Funahashi, H Amano

Proceedings Fourth International Symposium on Parallel Architectures … （IEEE COMPUTER SOC）     74 - 79 1999年

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

Recursive Diagonal Torus (RDT) is a class of interconnection network consisting of recursively overlaid two-dimensional square diagonal tori for massively parallel computers with up to 2(16) nodes. Connection structures of the RDT vary according to the assignment of tipper rank diagonal tori into a node: Although traditional simple assignment called RDT(2,4,1)/alpha shows enough performance under the uniform traffic, the congestion of low rank tori degrades the performance when local communication is dominant.
In this paper RDT(2,4,1)/beta torus assignment is proposed, focusing an improving the performance for local communication. With a simplified simulation algorithm, result shows that RDT(2,4,1)/beta improves the average distance compared with RDT(2,4,1)/alpha assignment when considering local area.

Adaptive routing on the recursive Diagonal torus

A Funahashi, T Hanawa, T Kudoh, H Amano

International Symposium on High Performance Computing, 171-182 1997年

研究論文（学術雑誌）, 共著, 査読有り

Fault Tolerance of the TBSF (Tandem Banyan Switching Fabrics) and PBSF (Piled Banyan Switching Fabrics)

FUNAHASHI Akira, HANAWA Toshihiro, AMANO Hideharu

IEICE transactions on information and systems （一般社団法人電子情報通信学会）  E79-D （ 8 ） 1180-1189 - 1189 1996年08月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  09168532

　概要を見る

Multistage Interconnection Networks (MIN) with multiple outlets are networks which can support higher bandwidth than those of nonblocking networks by passing multiple packets to the same destination. Fault recovery mechanisms are proposed for two of such networks (TBSF/PBSF) with the best use of their inherent fault tolerant capability. With these mechanisms, on-the-fly fault recovery is possible for multiple faults on switching elements. For the link fault, the networks are reconfigured after fault diagnosis, and the network is available with some performance degradation. The bandwidth degradation under multiple faults on link/element is analyzed with both theoretical models and simulation. Through the analysis, F-PBSF shows high fault tolerance under high traffic load and low reliability by using 3 or more banyan networks.

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