Nakaoka Shinji
| Faculty of Advanced Life Science Advanced Transdisciplinary Science Tissue Organization Science | Professor |
| Research Institute for Electronic Science Research Center of Mathematics for Social Creativity | Professor |
| Institute for the Promotion of Business-Regional Collaboration | Professor |
Last Updated :2025/12/04
■Researcher basic information
Profile Information
- Publications
http://scholar.google.co.jp/citations?user=U8IgYzMAAAAJ&hl=ja
Researchmap personal page
Home Page URL
Researcher number
- 30512040
J-Global ID
Research Field
Educational Organization
- Bachelor's degree program, School of Science
- Master's degree program, Graduate School of Life Science
- Doctoral (PhD) degree program, Graduate School of Life Science
■Career
Career
- Mar. 2025 - Present
Hokkaido University, Faculty of Advanced Life Science Division of Advanced Transdisciplinary Sciences, Professor - Mar. 2021 - Feb. 2025
Hokkaido University, Faculty of Advanced Life Science Laboratory of mathematical biology, Associate Professor, Japan - 2016 - 2018
科学技術振興機構, さきがけ, 専任研究員 - 2018
北海道大学大学院, 先端生命科学研究院, 特任講師 - 2016 - 2016
The University of Tokyo, Institute of Industrial Science, 特任助教 - 2014 - 2016
東京大学大学院, 医学系研究科, 助教 - 2013 - 2014
理化学研究所, 統合生命医科学研究センター, 上級研究員 - 2011 - 2013
理化学研究所, 免疫アレルギー科学総合研究センター, 上級研究員 - 2013
RIKEN, 研究員 - 2011 - 2011
科学技術振興機構, FIRST 合原複雑数理モデルプロジェクト, 研究員 - 2008 - 2011
日本学術振興会, 特別研究員, PD - 2007 - 2008
科学技術振興機構, ERATO 合原複雑数理モデルプロジェクト, 研究員
Educational Background
- 2004 - 2007, Shizuoka University, Graduate School of Science and Engineering, システム科学専攻, Japan
- 2002 - 2004, Osaka Prefecture University, Graduate School of Engineering, 数理情報学専攻(数理工学分野), Japan
- 1998 - 2002, Osaka Prefecture University, School of Engineering, Department of Mathematical Sciences, Japan
- 1995 - 1998, 大阪府立三国丘高校, Japan
■Research activity information
Papers
- Modeling alternative strategies of male emergence timing.
Hidaka Kubo, Shinji Nakaoka, Ryo Yamaguchi
Journal of theoretical biology, 612, 112214, 112214, 07 Sep. 2025, [International Magazine]
English, Scientific journal, In many butterfly species, males emerge earlier than females as part of a strategy to maximize male reproductive success. Although behavioral ecological studies using mathematical models have been conducted to explain this phenomenon, certain emergence patterns remain unexplained. In the butterfly species Fabriciana nerippe, some males emerge at the same time as females, in addition to males that emerge earlier than the females. However, it is unclear what emergence patterns occur in populations with male dimorphism, as observed in this species. In this study, we showed the existence of male body size dimorphism in Fabriciana nerippe by conducting a comparative analysis of forewing lengths between males and females. In addition, we developed a comprehensive mathematical model to investigate emergence patterns in the presence of dimorphic males. By introducing a trade-off between large size and early emergence, the model considered a scenario where small early-emerging and large late-emerging males could coexist. Numerical analysis demonstrated the emergence patterns of these two male types with a switch in emergence time. Furthermore, the higher the death rate before emergence, the earlier the emergence switch. These findings suggested that the timing of the switch depends on the death rate and is influenced by environmental factors. This work contributes to ecological and theoretical studies on two types of emergence timing in life-history strategies across a broader range of species. - Machine learning based characterization of high risk carriers of HTLV-1-associated myelopathy (HAM).
Md Ishtiak Rashid, Junya Sunagawa, Akari Matsuki, Asami Yamada, Toshiki Watanabe, Masako Iwanaga, Ki-Ryang Koh, Takafumi Shichijo, Masao Matsuoka, Jun-Ichirou Yasunaga, Shinji Nakaoka
Scientific reports, 15, 1, 25111, 25111, 11 Jul. 2025, [International Magazine]
English, Scientific journal, HTLV-1-associated myelopathy (HAM) develops in a part of HTLV-1-infected individuals while most of the individuals remain asymptomatic. This complicates the identification of HTLV-1 carriers at elevated risk. In this study, we integrated HTLV-1 proviral load and antibody titers against Tax, Env, Gag p15, p19, and p24 proteins in a machine learning (ML) framework to identify and characterize high-risk individuals likely to develop HAM. We stratified asymptomatic carrier samples employing an anomaly detection model. We further developed and validated classifier models capable of distinguishing three clinical subgroups, carrier, ATL, and HAM for assessing the anomaly carrier samples as unseen test data. With most anomaly carrier samples (~ 76.47%) predicted as HAM, further statistical and interpretative analysis revealed the 'HAM-like' characteristics of the anomaly carrier samples indicating elevated risk. Additionally, significant heterogeneity in immune response was observed among other asymptomatic carriers. As an exploratory, hypothesis-generating study, our findings are preliminary and aim to propose potential biomarkers and computational strategies that warrant validation in future longitudinal investigations. Our machine learning-based approach offers a novel and insightful tool for identifying and evaluating high-risk characteristics for HAM, providing a holistic view of the complex immune dynamics of asymptomatic carriers of HTLV-1. - Causal interactions among phytoplankton and Pseudo-nitzschia species revealed by empirical dynamic modelling
Ishara Uhanie Perera, So Fujiyoshi, Daiki Kumakura, Carolina Medel, Kyoko Yarimizu, Oscar Espinoza-González, Leonardo Guzmán, Shinji Nakaoka, Felipe Tucca, Alexander Jaramillo-Torres, Yukako Tohsato, Jacquelinne J. Acuña, Milko A. Jorquera, Hansoo Lee, Fumito Maruyama
Marine Pollution Bulletin, 211, 117432, 117432, Elsevier BV, Feb. 2025
Scientific journal - Sucrose-preferring gut microbes prevent host obesity by producing exopolysaccharides
Hidenori Shimizu, Junki Miyamoto, Keiko Hisa, Ryuji Ohue-Kitano, Hiromi Takada, Mayu Yamano, Akari Nishida, Daiki Sasahara, Yuki Masujima, Keita Watanabe, Shota Nishikawa, Sakura Takahashi, Takako Ikeda, Yuya Nakajima, Naofumi Yoshida, Chiaki Matsuzaki, Takuya Kageyama, Ibuki Hayashi, Akari Matsuki, Ryo Akashi, Seiichi Kitahama, Masako Ueyama, Takumi Murakami, Shinsuke Inuki, Junichiro Irie, Noriko Satoh-Asahara, Hirokazu Toju, Hiroshi Mori, Shinji Nakaoka, Tomoya Yamashita, Atsushi Toyoda, Kenji Yamamoto, Hiroaki Ohno, Takane Katayama, Hiroshi Itoh, Ikuo Kimura
Nature Communications, 16, 1, 1145, 1145, Springer Science and Business Media LLC, 29 Jan. 2025, [International Magazine]
English, Scientific journal, Commensal bacteria affect host health by producing various metabolites from dietary carbohydrates via bacterial glycometabolism; however, the underlying mechanism of action remains unclear. Here, we identified Streptococcus salivarius as a unique anti-obesity commensal bacterium. We found that S. salivarius may prevent host obesity caused by excess sucrose intake via the exopolysaccharide (EPS) -short-chain fatty acid (SCFA) -carbohydrate metabolic axis in male mice. Healthy human donor-derived S. salivarius produced high EPS levels from sucrose but not from other sugars. S. salivarius abundance was significantly decreased in human donors with obesity compared with that in healthy donors, and the EPS-SCFA bacterial carbohydrate metabolic process was attenuated. Our findings reveal an important mechanism by which host-commensal interactions in glycometabolism affect energy regulation, suggesting an approach for preventing lifestyle-related diseases via prebiotics and probiotics by targeting bacteria and EPS metabolites. - Prediction of cccDNA dynamics in hepatitis B patients by a combination of serum surrogate markers
Kwang Su Kim, Masashi Iwamoto, Kosaku Kitagawa, Hyeongki Park, Sanae Hayashi, Senko Tsukuda, Takeshi Matsui, Masanori Atsukawa, Kentaro Matsuura, Natthaya Chuaypen, Pisit Tangkijvanich, Lena Allweiss, Takara Nishiyama, Naotoshi Nakamura, Yasuhisa Fujita, Eiryo Kawakami, Shinji Nakaoka, Masamichi Muramatsu, Kazuyuki Aihara, Takaji Wakita, Alan S. Perelson, Maura Dandri, Koichi Watashi, Shingo Iwami, Yasuhito Tanaka
PLOS Computational Biology, 21, 1, e1012615, e1012615, Public Library of Science (PLoS), 09 Jan. 2025, [International Magazine]
English, Scientific journal, Quantification of intrahepatic covalently closed circular DNA (cccDNA) is a key for evaluating an elimination of hepatitis B virus (HBV) in infected patients. However, quantifying cccDNA requires invasive methods such as a liver biopsy, which makes it impractical to access the dynamics of cccDNA in patients. Although HBV RNA and HBV core-related antigens (HBcrAg) have been proposed as surrogate markers for evaluating cccDNA activity, they do not necessarily estimate the amount of cccDNA. Here, we employed a recently developed multiscale mathematical model describing intra- and intercellular viral propagation and applied it in HBV-infected patients under treatment. We developed a model that can predict intracellular HBV dynamics by use of extracellular viral markers, including HBsAg, HBV DNA, and HBcrAg in peripheral blood. Importantly, the model prediction of the amount of cccDNA in patients over time was confirmed to be well correlated with the data for quantified cccDNA by paired liver biopsy. Thus, our method combining classic and emerging surrogate markers enables us to predict the decay dynamics of cccDNA in patients undergoing treatment. - Association between oral frailty and Prevotella percentage in the oral microbiota of community-dwelling older adults who participated in the CHEER Iwamizawa project, Japan.
Chizuru Kimura, Kazuhito Miura, Yutaka Watanabe, Haruhisa Baba, Kimiya Ozaki, Akira Hasebe, Tokiyoshi Ayabe, Kiminori Nakamura, Shinji Nakaoka, Katsuhiko Ogasawara, Teppei Suzuki, Hiroshi Saito, Takashi Kimura, Akiko Tamakoshi, Yutaka Yamazaki
Journal of oral rehabilitation, 51, 9, 1721, 1729, 08 Jun. 2024, [International Magazine]
English, Scientific journal, BACKGROUND: Prevotella bacteria are associated with inherent diseases of the oral cavity, such as periodontal disease, and systemic diseases. Oral frailty (OF) has been associated with nursing necessity and death. However, the relationship between OF and oral microbiota has not been fully clarified. OBJECTIVE: This cross-sectional study investigated the association between OF and Prevotella percentage in the oral microbiota of community-dwelling older adults. METHODS: Oral bacteria species from saliva were identified in 208 community-dwelling older individuals aged ≥60 years in Japan. The proportion of Prevotella in the oral microbiota was classified into three tertile groups, and its relationship with each test item for OF (number of remaining teeth, masticatory performance, oral diadochokinesis, tongue pressure, difficulties eating tough foods, difficulties swallowing tea or soup, number of applicable OF judgement items, and existence of OF) was examined using ordinal logistic regression analysis. RESULTS: The Prevotella proportions were classified into lower, middle and upper groups, comprising 70, 69 and 69 participants, respectively. The three groups showed a significant relationship between the number of remaining teeth (odds ratio [OR]: 0.946, 95% confidence interval [CI]: 0.915-0.977), masticatory performance (OR: 0.897, 95% CI: 0.844-0.953), number of applicable OF judgement items (OR: 1.477, 95% CI: 1.14-1.915), and existence of OF (OR: 4.194, 95% CI: 1.519-11.576). CONCLUSION: The proportion of Prevotella in oral microbiota was high in individuals with OF. Among the older adults, the type of oral microbiota and systemic diseases may be related to the examination and management of oral function decline. - Multiscale modeling of HBV infection integrating intra- and intercellular viral propagation to analyze extracellular viral markers
Kosaku Kitagawa, Kwang Su Kim, Masashi Iwamoto, Sanae Hayashi, Hyeongki Park, Takara Nishiyama, Naotoshi Nakamura, Yasuhisa Fujita, Shinji Nakaoka, Kazuyuki Aihara, Alan S. Perelson, Lena Allweiss, Maura Dandri, Koichi Watashi, Yasuhito Tanaka, Shingo Iwami
PLOS Computational Biology, 20, 3, e1011238, e1011238, Public Library of Science (PLoS), 11 Mar. 2024, [International Magazine]
English, Scientific journal, Chronic infection with hepatitis B virus (HBV) is caused by the persistence of closed circular DNA (cccDNA) in the nucleus of infected hepatocytes. Despite available therapeutic anti-HBV agents, eliminating the cccDNA remains challenging. Thus, quantifying and understanding the dynamics of cccDNA are essential for developing effective treatment strategies and new drugs. However, such study requires repeated liver biopsy to measure the intrahepatic cccDNA, which is basically not accepted because liver biopsy is potentially morbid and not common during hepatitis B treatment. We here aimed to develop a noninvasive method for quantifying cccDNA in the liver using surrogate markers in peripheral blood. We constructed a multiscale mathematical model that explicitly incorporates both intracellular and intercellular HBV infection processes. The model, based on age-structured partial differential equations, integrates experimental data from in vitro and in vivo investigations. By applying this model, we roughly predicted the amount and dynamics of intrahepatic cccDNA within a certain range using specific viral markers in serum samples, including HBV DNA, HBsAg, HBeAg, and HBcrAg. Our study represents a significant step towards advancing the understanding of chronic HBV infection. The noninvasive quantification of cccDNA using our proposed method holds promise for improving clinical analyses and treatment strategies. By comprehensively describing the interactions of all components involved in HBV infection, our multiscale mathematical model provides a valuable framework for further research and the development of targeted interventions. - An energy landscape approach reveals the potential key bacteria contributing to the development of inflammatory bowel disease.
Kaiyang Zhang, Shinji Nakaoka
PloS one, 19, 6, e0302151, 2024, [International Magazine]
English, Scientific journal, The dysbiosis of microbiota has been reported to be associated with numerous human pathophysiological processes, including inflammatory bowel disease (IBD). With advancements in high-throughput sequencing, various methods have been developed to study the alteration of microbiota in the development and progression of diseases. However, a suitable approach to assess the global stability of the microbiota in disease states through time-series microbiome data is yet to be established. In this study, we have introduced a novel Energy Landscape construction method, which incorporates the Latent Dirichlet Allocation (LDA) model and the pairwise Maximum Entropy (MaxEnt) model for their complementary advantages, and demonstrate its utility by applying it to an IBD time-series dataset. Through this approach, we obtained the microbial assemblages' energy profile of the whole microbiota under the IBD condition and uncovered the hidden stable stages of microbiota structure during the disease development with time-series microbiome data. The Bacteroides-dominated assemblages presenting in multiple stable states suggest the potential contribution of Bacteroides and interactions with other microbial genera, like Alistipes, and Faecalibacterium, to the development of IBD. Our proposed method provides a novel and insightful tool for understanding the alteration and stability of the microbiota under disease states and offers a more holistic view of the complex dynamics at play in microbiota-mediated diseases. - Anti-HTLV-1 immunity combined with proviral load as predictive biomarkers for adult T-cell leukemia-lymphoma.
Asami Yamada, Jun-Ichirou Yasunaga, Lihan Liang, Wenyi Zhang, Junya Sunagawa, Shinji Nakaoka, Shingo Iwami, Yasunori Kogure, Yuta Ito, Keisuke Kataoka, Masanori Nakagawa, Masako Iwanaga, Atae Utsunomiya, Ki-Ryang Koh, Toshiki Watanabe, Kisato Nosaka, Masao Matsuoka
Cancer science, 115, 1, 310, 320, 10 Nov. 2023, [International Magazine]
English, Scientific journal, Human T-cell leukemia virus type 1 (HTLV-1) establishes chronic infection in humans and induces a T-cell malignancy called adult T-cell leukemia-lymphoma (ATL) and several inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Persistent HTLV-1 infection is established under the pressure of host immunity, and therefore the immune response against HTLV-1 is thought to reflect the status of the disease it causes. Indeed, it is known that cellular immunity against viral antigens is suppressed in ATL patients compared to HAM/TSP patients. In this study, we show that profiling the humoral immunity to several HTLV-1 antigens, such as Gag, Env, and Tax, and measuring proviral load are useful tools for classifying disease status and predicting disease development. Using targeted sequencing, we found that several carriers whom this profiling method predicted to be at high risk for developing ATL indeed harbored driver mutations of ATL. The clonality of HTLV-1-infected cells in those carriers was still polyclonal; it is consistent with an early stage of leukemogenesis. Furthermore, this study revealed significance of anti-Gag proteins to predict high risk group in HTLV-1 carriers. Consistent with this finding, anti-Gag cytotoxic T lymphocytes (CTLs) were increased in patients who received hematopoietic stem cell transplantation and achieved remission state, indicating the significance of anti-Gag CTLs for disease control. Our findings suggest that our strategy that combines anti-HTLV-1 antibodies and proviral load may be useful for prediction of the development of HTLV-1-associated diseases. - Disentangling the growth curve of microbial culture
Daiki Kumakura, Ryo Yamaguchi, Akane Hara, Shinji Nakaoka
Journal of Theoretical Biology, 573, 111597, 111597, Elsevier BV, Aug. 2023, [International Magazine]
English, Scientific journal, Many researchers have studied the population dynamics of microbe of microbes as a typical example of population dynamics. The Monod equation, which mainly focuses on the growth and stationary phases, is used when plotting a growth curve. However, the growth potential in the late stage of culture has been overlooked. Previous studies considered the direct degradation of products to the limiting substrate. In this study, we considered microbial growth during the stationary phase, which enables us to describe the dynamics precisely. The microbes were divided into two populations: one grew by consuming the limiting substrate and the other degraded the products by metabolism. According to the numerical analysis of our model, microbes may choose one of two strategies: one consumes substrates and expands quickly, and the other grows slowly while cleaning up the environment in which they thrive. Furthermore, we found three types of microbial growth depending on their ability to detect metabolite accumulation. Using experimentally measured data, this model can estimate the dynamics of cell density, the substrates, and the metabolites used. The model's disentangling of growth curves offers novel interpretive possibilities for culture system dynamics. - Comparison of RNA-Seq analysis data between tracheal mite-infested and uninfested Japanese honey bees (Apis cerana japonica).
Akihiko Suzuki, Masaki Kamakura, Takuya Shiramata, Shinji Nakaoka, Yoshiko Sakamoto
BMC research notes, 16, 1, 122, 122, 26 Jun. 2023, [International Magazine]
English, Scientific journal, OBJECTIVE: The purpose of this data set is to investigate differences in RNA-Seq transcriptome profiles between Acarapis woodi-infested and uninfested Japanese honey bees (Apis cerana japonica). The data set is strengthened by data collected from different body parts (head, thorax, and abdomen). The data set will support future studies of molecular biological changes in mite-infested honey bees. DATA DESCRIPTION: We collected 5 mite-infested and 5 uninfested A. cerana japonica workers from each of 3 different colonies (designated as A, B, and C). Workers were dissected into 3 body sites (i.e., heads, thoraces, and abdomen), and 5 of each body site were pooled together for RNA extraction, generating a total of 18 RNA-Seq samples (2 infection status × 3 colonies × 3 body sites). FASTQ data files of each sample that were generated by a DNBSEQ-G400 sequencer with the 2 × 100 bp paired-end sequencing protocol are available in the DDBJ Sequence Read Archive under accession number DRA015087 (RUN: DRR415616-DRR415633, BioProject: PRJDB14726, BioSample: SAMD00554139-SAMD00554156, Experiment: DRX401183-DRX401200). The data set is a fine-scale analysis of gene expression in the mite-infested A. cerana japonica workers because 18 RNA-Seq samples are separated by 3 body sites. - 岩見沢市母子健康調査(SMILE Iwamizawa)における妊娠期から出産後の母体腸内細菌叢解析
和泉 裕久, 両角 麻衣, 田畑 風華, 川上 智美, 武田 安弘, 宮地 一裕, 中村 公則, 綾部 時芳, 中岡 慎治, 相沢 智康, 中村 宝弘, 木村 尚史, 中村 幸志, 玉腰 暁子
腸内細菌学雑誌, 37, 2, 122, 122, (公財)腸内細菌学会, Apr. 2023
Japanese - 岩見沢市母子健康調査(SMILE Iwamizawa)における乳児の腸内細菌叢解析
両角 麻衣, 和泉 裕久, 田畑 風華, 川上 智美, 武田 安弘, 宮地 一裕, 中村 公則, 綾部 時芳, 中岡 慎治, 相沢 智康, 中村 宝弘, 木村 尚史, 中村 幸志, 玉腰 暁子
腸内細菌学雑誌, 37, 2, 123, 123, (公財)腸内細菌学会, Apr. 2023
Japanese - Data mining for prediction and interpretation of bacterial population behavior in food
Junpei Hosoe, Junya Sunagawa, Shinji Nakaoka, Shige Koseki, Kento Koyama
Frontiers in Food Science and Technology, 2, Frontiers Media SA, 15 Dec. 2022
Scientific journal, Although bacterial population behavior has been investigated in a variety of foods in the past 40 years, it is difficult to obtain desired information from the mere juxtaposition of experimental data. We predicted the changes in the number of bacteria and visualize the effects of pH, aw, and temperature using a data mining approach. Population growth and inactivation data on eight pathogenic and food spoilage bacteria under 5,025 environmental conditions were obtained from the ComBase database (www.combase.cc), including 15 food categories, and temperatures ranging from 0°C to 25°C. The eXtreme gradient boosting tree was used to predict population behavior. The root mean square error of the observed and predicted values was 1.23 log CFU/g. The data mining model extracted the growth inhibition for the investigated bacteria against aw, temperature, and pH using the SHapley Additive eXplanations value. A data mining approach provides information concerning bacterial population behavior and how food ecosystems affect bacterial growth and inactivation. - COVID-19-related stress, exercise, and oral health-related quality of life among community-dwelling older adults who participated in the CHEER Iwamizawa project, Japan.
Kazuhito Miura, Yutaka Watanabe, Haruhisa Baba, Kimiya Ozaki, Takae Matsushita, Miyako Kondoh, Kazutaka Okada, Shinji Nakaoka, Katsuhiko Ogasawara, Teppei Suzuki, Hiroshi Saito, Takashi Kimura, Akiko Tamakoshi, Yutaka Yamazaki
Scientific reports, 12, 1, 20347, 20347, 27 Nov. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, This study examined the association between coronavirus disease 2019 (COVID-19)-related stress, exercise habits, and oral health-related quality of life (OHRQoL) in a sample of 215 community-dwelling older adults in Japan (57 men, 158 women; Mage = 74.2 years, SD = 6.0). Data were collected during wellness checkups in October 2020 and included participants' demographic characteristics, measures of instrumental activities of daily living and depressive tendencies, number of teeth, oral hypofunction, OHRQoL, COVID-19-related stress, and exercise habits. Four mutually exclusive groups were created, using the presence or absence of COVID-19-related stress and lack of exercise habits as risk factors for poor OHRQoL (no COVID-19-related stress and no lack of exercise, COVID-19-related stress only, lack of exercise habits only, and both COVID-19-related stress and lack of exercise habits). Poisson regression with robust standard errors provided the prevalence ratio for poor OHRQoL. The presence of both COVID-19-related stress and lack of exercise habits (adjusted prevalence ratio: 2.20, 95% CI: 1.31- 3.69) was associated with poor OHRQoL. The results indicate that COVID-19-related stress and exercise habits should be considered when designing oral health and public health initiatives. - Evolving neural networks through bio-inspired parent selection in dynamic environments.
Junya Sunagawa, Ryo Yamaguchi, Shinji Nakaoka
Bio Systems, 218, 104686, 104686, 04 May 2022, [International Magazine]
English, Scientific journal, Environmental variability often degrades the performance of algorithms designed to capture the global convergence of a given search space. Several approaches have been developed to challenge environmental uncertainty by incorporating biologically inspired notions, focusing on crossover, mutation, and selection. This study proposes a bio-inspired approach called NEAT-HD, which focuses on parent selection based on genetic similarity. The originality of the proposed approach rests on its use of a sigmoid function to accelerate species formation and contribute to population diversity. Experiments on two classic control tasks were performed to demonstrate the performance of the proposed method. The results show that NEAT-HD can dynamically adapt to its environment by forming hybrid individuals originating from genetically distinct parents. Additionally, an increase in diversity within the population was observed due to the formation of hybrids and novel individuals, which has never been observed before. Comparing two tasks, the characteristics of NEAT-HD were improved by appropriately setting the algorithm to include the distribution of genetic distance within the population. Our key finding is the inherent potential of newly formed individuals for robustness against dynamic environments. - Analysis of the Pancreatic Cancer Microbiome Using Endoscopic Ultrasound-Guided Fine-Needle Aspiration-Derived Samples.
Shintaro Nakano, Yasuyuki Kawamoto, Yoshito Komatsu, Rika Saito, Ken Ito, Takahiro Yamamura, Kazuaki Harada, Satoshi Yuki, Kazumichi Kawakubo, Ryo Sugiura, Shin Kato, Koji Hirata, Hajime Hirata, Masahito Nakajima, Ryutaro Furukawa, Yunosuke Takishin, Kousuke Nagai, Isao Yokota, Keisuke H Ota, Shinji Nakaoka, Masaki Kuwatani, Naoya Sakamoto
Pancreas, 51, 4, 351, 357, 01 Apr. 2022, [International Magazine]
English, Scientific journal, OBJECTIVES: Most previous studies have analyzed bacteria in tumors using resected pancreatic cancer (PC) tissues, because it is difficult to obtain tissue samples from unresectable advanced PC. We aimed to determine whether minimal tissue obtained by endoscopic ultrasound-guided fine-needle aspiration is useful for microbiome analysis. METHODS: Thirty PC and matched duodenal and stomach tissues (N = 90) were prospectively collected from 30 patients who underwent endoscopic ultrasound-guided fine-needle aspiration. Bacterial DNA was extracted, and 16S rRNA sequencing was performed. The primary outcome was the success rate of bacterial detection in tumors. Bacterial diversity and structure were investigated. RESULTS: The bacterial detection rates were 80%, 100%, and 97% in PC, gastric, and duodenal samples, respectively. Pancreatic cancer tissues showed a lower α-diversity and a significantly different microbial structure than stomach and duodenal tissues. Proteobacteria were more abundant, whereas Firmicutes, Bacteroidetes, and Fusobacteria were less abundant in PC tissues than in stomach and duodenal tissues. Acinetobacter was more abundant in PC tissues than in stomach and duodenal tissues, and Delftia was more frequently detected in resectable PC. CONCLUSIONS: Endoscopic ultrasound-guided fine-needle aspiration samples were valuable for PC microbiome analysis, revealing that the bacterial composition of PC is different from that of the stomach and duodenum. - Antithetic effect of interferon-α on cell-free and cell-to-cell HIV-1 infection.
Ryuichi Kumata, Shoya Iwanami, Katrina B Mar, Yusuke Kakizoe, Naoko Misawa, Shinji Nakaoka, Yoshio Koyanagi, Alan S Perelson, John W Schoggins, Shingo Iwami, Kei Sato
PLoS computational biology, 18, 4, e1010053, Apr. 2022, [International Magazine]
English, Scientific journal, In HIV-1-infected individuals, transmitted/founder (TF) virus contributes to establish new infection and expands during the acute phase of infection, while chronic control (CC) virus emerges during the chronic phase of infection. TF viruses are more resistant to interferon-alpha (IFN-α)-mediated antiviral effects than CC virus, however, its virological relevance in infected individuals remains unclear. Here we perform an experimental-mathematical investigation and reveal that IFN-α strongly inhibits cell-to-cell infection by CC virus but only weakly affects that by TF virus. Surprisingly, IFN-α enhances cell-free infection of HIV-1, particularly that of CC virus, in a virus-cell density-dependent manner. We further demonstrate that LY6E, an IFN-stimulated gene, can contribute to the density-dependent enhancement of cell-free HIV-1 infection. Altogether, our findings suggest that the major difference between TF and CC viruses can be explained by their resistance to IFN-α-mediated inhibition of cell-to-cell infection and their sensitivity to IFN-α-mediated enhancement of cell-free infection. - Oral frailty and carriage of oral Candida in community-dwelling older adults (Check-up to discover Health with Energy for senior Residents in Iwamizawa; CHEER Iwamizawa).
Haruhisa Baba, Yutaka Watanabe, Kazuhito Miura, Kimiya Ozaki, Takae Matsushita, Miyako Kondoh, Kazutaka Okada, Akira Hasebe, Tokiyoshi Ayabe, Kiminori Nakamura, Shinji Nakaoka, Katsuhiko Ogasawara, Teppei Suzuki, Hiroshi Saito, Takashi Kimura, Akiko Tamakoshi, Yutaka Yamazaki
Gerodontology, 39, 1, 49, 58, Mar. 2022, [International Magazine]
English, Scientific journal, OBJECTIVE: To examine the association between oral frailty and oral Candida carriage as a general indicator of deteriorating oral function in older adults. BACKGROUND: Older adults exhibit an elevated risk of oral candidiasis caused by Candida. Although many studies have identified factors associated with oral Candida carriage, none have evaluated its relationship with oral function. MATERIALS AND METHODS: This study included 210 community-dwelling older adults aged ≥60 years who participated in wellness checks. Fungal flora expression in saliva samples was evaluated to identify oral C. albicans and C. glabrata. Participants were categorised by detection of neither strain (group 1), either one of the strains (group 2), or both strains (group 3). The relationship between oral Candida carriage and oral frailty was evaluated by multinomial logistic regression analysis. RESULTS: The participants included 58 men and 152 women with a mean age of 74.2 ± 6.1 years. A total of 88 (41.9%), 94 (44.8%) and 28 (13.3%) participants were assigned to groups 1, 2 and 3 respectively. In the multinomial logistic regression analysis, significant associations were observed between group 1 and group 2 for "Have you choked on your tea or soup recently?" and the number of applicable oral frailty items. Between group 1 and group 3, significant associations were observed for the number of remaining teeth, masticatory performance and the number of applicable oral frailty items. CONCLUSION: We obtained basic data useful for intervention studies aimed at verifying whether oral function management prevents deterioration of the oral bacterial flora. - Chemical-Mediated Microbial Interactions Can Reduce the Effectiveness of Time-Series-Based Inference of Ecological Interaction Networks.
Kenta Suzuki, Masato S Abe, Daiki Kumakura, Shinji Nakaoka, Fuki Fujiwara, Hirokuni Miyamoto, Teruno Nakaguma, Mashiro Okada, Kengo Sakurai, Shohei Shimizu, Hiroyoshi Iwata, Hiroshi Masuya, Naoto Nihei, Yasunori Ichihashi
International journal of environmental research and public health, 19, 3, 22 Jan. 2022, [International Magazine]
English, Scientific journal, Network-based assessments are important for disentangling complex microbial and microbial-host interactions and can provide the basis for microbial engineering. There is a growing recognition that chemical-mediated interactions are important for the coexistence of microbial species. However, so far, the methods used to infer microbial interactions have been validated with models assuming direct species-species interactions, such as generalized Lotka-Volterra models. Therefore, it is unclear how effective existing approaches are in detecting chemical-mediated interactions. In this paper, we used time series of simulated microbial dynamics to benchmark five major/state-of-the-art methods. We found that only two methods (CCM and LIMITS) were capable of detecting interactions. While LIMITS performed better than CCM, it was less robust to the presence of chemical-mediated interactions, and the presence of trophic competition was essential for the interactions to be detectable. We show that the existence of chemical-mediated interactions among microbial species poses a new challenge to overcome for the development of a network-based understanding of microbiomes and their interactions with hosts and the environment. - Energy landscape analysis elucidates the multistability of ecological communities across environmental gradients
Kenta Suzuki, Shinji Nakaoka, Shinji Fukuda, Hiroshi Masuya
ECOLOGICAL MONOGRAPHS, 91, 3, Aug. 2021
English, Scientific journal - Detection of significant antiviral drug effects on COVID-19 with reasonable sample sizes in randomized controlled trials: A modeling study.
Shoya Iwanami, Keisuke Ejima, Kwang Su Kim, Koji Noshita, Yasuhisa Fujita, Taiga Miyazaki, Shigeru Kohno, Yoshitsugu Miyazaki, Shimpei Morimoto, Shinji Nakaoka, Yoshiki Koizumi, Yusuke Asai, Kazuyuki Aihara, Koichi Watashi, Robin N Thompson, Kenji Shibuya, Katsuhito Fujiu, Alan S Perelson, Shingo Iwami, Takaji Wakita
PLoS medicine, 18, 7, e1003660, Jul. 2021, [International Magazine]
English, Scientific journal, BACKGROUND: Development of an effective antiviral drug for Coronavirus Disease 2019 (COVID-19) is a global health priority. Although several candidate drugs have been identified through in vitro and in vivo models, consistent and compelling evidence from clinical studies is limited. The lack of evidence from clinical trials may stem in part from the imperfect design of the trials. We investigated how clinical trials for antivirals need to be designed, especially focusing on the sample size in randomized controlled trials. METHODS AND FINDINGS: A modeling study was conducted to help understand the reasons behind inconsistent clinical trial findings and to design better clinical trials. We first analyzed longitudinal viral load data for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) without antiviral treatment by use of a within-host virus dynamics model. The fitted viral load was categorized into 3 different groups by a clustering approach. Comparison of the estimated parameters showed that the 3 distinct groups were characterized by different virus decay rates (p-value < 0.001). The mean decay rates were 1.17 d-1 (95% CI: 1.06 to 1.27 d-1), 0.777 d-1 (0.716 to 0.838 d-1), and 0.450 d-1 (0.378 to 0.522 d-1) for the 3 groups, respectively. Such heterogeneity in virus dynamics could be a confounding variable if it is associated with treatment allocation in compassionate use programs (i.e., observational studies). Subsequently, we mimicked randomized controlled trials of antivirals by simulation. An antiviral effect causing a 95% to 99% reduction in viral replication was added to the model. To be realistic, we assumed that randomization and treatment are initiated with some time lag after symptom onset. Using the duration of virus shedding as an outcome, the sample size to detect a statistically significant mean difference between the treatment and placebo groups (1:1 allocation) was 13,603 and 11,670 (when the antiviral effect was 95% and 99%, respectively) per group if all patients are enrolled regardless of timing of randomization. The sample size was reduced to 584 and 458 (when the antiviral effect was 95% and 99%, respectively) if only patients who are treated within 1 day of symptom onset are enrolled. We confirmed the sample size was similarly reduced when using cumulative viral load in log scale as an outcome. We used a conventional virus dynamics model, which may not fully reflect the detailed mechanisms of viral dynamics of SARS-CoV-2. The model needs to be calibrated in terms of both parameter settings and model structure, which would yield more reliable sample size calculation. CONCLUSIONS: In this study, we found that estimated association in observational studies can be biased due to large heterogeneity in viral dynamics among infected individuals, and statistically significant effect in randomized controlled trials may be difficult to be detected due to small sample size. The sample size can be dramatically reduced by recruiting patients immediately after developing symptoms. We believe this is the first study investigated the study design of clinical trials for antiviral treatment using the viral dynamics model. - Development of a rapid scabies immunodiagnostic assay based on transcriptomic analysis of Sarcoptes scabiei var. nyctereutis.
Teruo Akuta, Daisuke Minegishi, Nobuhide Kido, Keitaro Imaizumi, Shinji Nakaoka, Shin-Ichiro Tachibana, Kenji Hikosaka, Fumi Hori, Masataka, Nakagawa, Chiaki Sakuma, Yuki Oouchi, Yu Nakajima, Sohei Tanaka, Tomoko Omiya, Kouki Morikaku, Minori Kawahara, Yoshifumi Tada, Hiroshi Tarui, Takafumi Ueda, Takane Kikuchi-Ueda, Yasuo Ono
Scientific reports, 11, 1, 6455, 6455, 19 Mar. 2021, [International Magazine]
English, Scientific journal, Scabies is a highly contagious skin disease caused by the mite Sarcoptes scabiei that affects many mammals. However, the sensitivity of traditional tests for scabies diagnosis in humans is less than 50%. To simplify the diagnosis of scabies, methods that are simple, sensitive, specific, and cost-effective are required. We developed an immunodiagnostic test based on S. scabiei var. nyctereutis RNA-seq data collected from Japanese raccoon dogs with sarcoptic mange. Three candidate antigens-a highly expressed hypothetical protein "QR98_0091190," another mite allergen known as "SMIPP-Cc," and an abundant "vitellogenin-like protein"-were evaluated by western-blot analysis. A lateral flow immunoassay, using specific antibodies against the vitellogenin-like protein, successfully detected scabies in the skin flakes of S. scabiei-infected raccoon dogs. This assay can potentially diagnose scabies more accurately in wildlife, as well as in humans. - A quantitative model used to compare within-host SARS-CoV-2, MERS-CoV, and SARS-CoV dynamics provides insights into the pathogenesis and treatment of SARS-CoV-2.
Kwang Su Kim, Keisuke Ejima, Shoya Iwanami, Yasuhisa Fujita, Hirofumi Ohashi, Yoshiki Koizumi, Yusuke Asai, Shinji Nakaoka, Koichi Watashi, Kazuyuki Aihara, Robin N Thompson, Ruian Ke, Alan S Perelson, Shingo Iwami
PLoS biology, 19, 3, e3001128, Mar. 2021, [International Magazine]
English, Scientific journal, The scientific community is focused on developing antiviral therapies to mitigate the impacts of the ongoing novel coronavirus disease 2019 (COVID-19) outbreak. This will be facilitated by improved understanding of viral dynamics within infected hosts. Here, using a mathematical model in combination with published viral load data, we compare within-host viral dynamics of SARS-CoV-2 with analogous dynamics of MERS-CoV and SARS-CoV. Our quantitative analyses using a mathematical model revealed that the within-host reproduction number at symptom onset of SARS-CoV-2 was statistically significantly larger than that of MERS-CoV and similar to that of SARS-CoV. In addition, the time from symptom onset to the viral load peak for SARS-CoV-2 infection was shorter than those of MERS-CoV and SARS-CoV. These findings suggest the difficulty of controlling SARS-CoV-2 infection by antivirals. We further used the viral dynamics model to predict the efficacy of potential antiviral drugs that have different modes of action. The efficacy was measured by the reduction in the viral load area under the curve (AUC). Our results indicate that therapies that block de novo infection or virus production are likely to be effective if and only if initiated before the viral load peak (which appears 2-3 days after symptom onset), but therapies that promote cytotoxicity of infected cells are likely to have effects with less sensitivity to the timing of treatment initiation. Furthermore, combining a therapy that promotes cytotoxicity and one that blocks de novo infection or virus production synergistically reduces the AUC with early treatment. Our unique modeling approach provides insights into the pathogenesis of SARS-CoV-2 and may be useful for development of antiviral therapies. - Early Dynamics of Chronic Myeloid Leukemia on Nilotinib Predicts Deep Molecular Response
Yuji Okamoto, Mitsuhito Hirano, Kai Morino, Masashi K. Kajita, Shinji Nakaoka, Mayuko Tsuda, Kei-ji Sugimoto, Shigehisa Tamaki, Junichi Hisatake, Hisayuki Yokoyama, Tadahiko Igarashi, Atsushi Shinagawa, Takeaki Sugawara, Satoru Hara, Kazuhisa Fujikawa, Seiichi Shimizu, Toshiaki Yujiri, Hisashi Wakita, Kaichi Nishiwaki, Arinobu Tojo, Kazuyuki Aihara
NPJ systems biology and applications, 8, 1, 39, 39, Cold Spring Harbor Laboratory, 17 Feb. 2021, [International Magazine]
English, Scientific journal,Abstract Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by theBCR-ABL1 tyrosine kinase1,2.ABL1 -selective tyrosine kinase inhibitors (TKIs) including nilotinib have dramatically improved the prognosis of patients with CML3–7. The ultimate goal of CML treatment is likely to be TKI-free maintenance of deep molecular response (DMR), which is defined by quantitative measurement ofBCR-ABL1 transcripts on the international scale (IS)8, and durable DMR is a prerequisite to reach this goal9. Thus, an algorithm to enable the early prediction of DMR achievement on TKI therapy is quite valuable. Here, we show that our mathematical framework based on a clinical trial dataset10 can accurately predict the response to frontline nilotinib. We found that our simple dynamical model can predict nilotinib response by using two common laboratory findings (observation values): IS11,12 and white blood cell (WBC) count. Furthermore, our proposed method identified patients who failed to achieve DMR with high fidelity according to the data collected only at three initial time points during nilotinib therapy. Since our model relies on the general properties of TKI response, our framework would be applicable to CML patients who receive frontline nilotinib or other TKIs in clinical practice.Significance Statement Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by the BCR-ABL1 tyrosine kinase. The goal of this treatment is the sequential achievement of deep molecular response (DMR). Tyrosine kinase inhibitors (TKIs) are effective in the reduction because they inhibit CML cell proliferation. However, because of individual differences in the TKI efficacy, some patients are unable to achieve DMR, so that early prediction of DMR reachability is necessary for personalized medicine. By combining time series analysis and mathematical modeling, we developed a mathematical method that accurately predicts patients who do not achieve DMR in the early stages of TKI administration. Our prediction method gives a basis of effective personalized treatments for CML patients. - Exploring Similarity Between Embedding Dimension of Time-Series Data and Flows of an Ecological Population Model
Daiki Kumakura, Shinji Nakaoka
Springer Proceedings in Mathematics and Statistics, 370, 69, 80, Springer, 2021
English, International conference proceedings - Dynamic Associations of Milk Components With the Infant Gut Microbiome and Fecal Metabolites in a Mother-Infant Model by Microbiome, NMR Metabolomic, and Time-Series Clustering Analyses.
Yosuke Komatsu, Daiki Kumakura, Namiko Seto, Hirohisa Izumi, Yasuhiro Takeda, Yuki Ohnishi, Shinji Nakaoka, Tomoyasu Aizawa
Frontiers in nutrition, 8, 813690, 813690, 2021, [International Magazine]
English, Scientific journal, Background: The gut microbiome and fecal metabolites of breastfed infants changes during lactation, and are influenced by breast milk components. This study aimed to investigate dynamic associations of milk components with the infant gut microbiome and fecal metabolites throughout the lactation period in a mother-infant model. Methods: One month after delivery, breast milk and subsequent infant feces were collected in a pair for 5 months from a mother and an exclusively breastfed infant. Composition of the fecal microbiome was determined with 16S rRNA sequencing. Low-molecular-weight metabolites, including human milk oligosaccharides (HMOs), and antibacterial proteins were measured in feces and milk using 1H NMR metabolomics and enzyme-linked immunosorbent assays. The association of milk bioactive components with the infant gut microbiome and fecal metabolites was determined with Python clustering and correlation analyses. Results: The HMOs in milk did not fluctuate throughout the lactation period. However, they began to disappear in infant feces at the beginning of month 4. Notably, at this time-point, a bifidobacterium species switching (from B. breve to B. longum subsp. infantis) occurred, accompanied by fluctuations in several metabolites including acetate and butyrate in infant feces. Conclusions: Milk bioactive components, such as HMOs, might play different roles in the exclusively breastfed infants depending on the lactation period. - Modeling Borna Disease Virus In Vitro Spread Reveals the Mode of Antiviral Effect Conferred by an Endogenous Bornavirus-Like Element.
Kwang Su Kim, Yusuke Yamamoto, Shinji Nakaoka, Keizo Tomonaga, Shingo Iwami, Tomoyuki Honda
Journal of virology, 94, 21, 14 Oct. 2020, [International Magazine]
English, Scientific journal, Endogenous retroviruses have demonstrated exaptation during long-term evolution with hosts, e.g., resulting in acquisition of antiviral effect on related extant viral infections. While empirical studies have found that an endogenous bornavirus-like element derived from viral nucleoprotein (itEBLN) in the ground squirrel genome shows antiviral effect on virus replication and de novo infection, the antiviral mechanism, dynamics, and quantitative effect of itEBLN remain unknown. In this study, we experimentally and theoretically investigated the dynamics of how an extant bornavirus, Borna disease virus 1 (BoDV-1), spreads and replicates in uninfected, BoDV-1-infected, and itEBLN-expressing cultured cells. Quantifying antiviral effect based on time course data sets, we found that the antiviral effects of itEBLN are estimated to be 75% and 34% on intercellular virus spread and intracellular virus replication, respectively. This discrepancy between intercellular virus spread and intracellular viral replication suggests that viral processes other than the replication of viral ribonucleoprotein complex (RNP) contributed to the suppression of virus spread in itEBLN-expressing cells. Because itEBLN binds to the BoDV-1 RNP, the suppression of viral RNP trafficking can be an attractive candidate explaining this discrepancy.IMPORTANCE Accumulating evidence suggests that some endogenous viral elements (EVEs), including endogenous retroviruses and endogenous nonretroviral virus elements, have acquired functions in the host as a result of long-term coevolution. Recently, an endogenous bornavirus-like element (itEBLN) found in the ground squirrel genome has been shown to have antiviral activity against exogenous bornavirus infection. In this study, we first quantified bornavirus spread in cultured cells and then calculated the antiviral activity of itEBLN on bornavirus infection. The calculated antiviral activity of itEBLN suggests its suppression of multiple processes in the viral life cycle. To our knowledge, this is the first study quantifying the antiviral activity of EVEs and speculating on a model of how some EVEs have acquired antiviral activity during host-virus arms races. - Quantifying the antiviral effect of APOBEC3 on HIV-1 infection in humanized mouse model
Tatsuya Kurusu, Kwang Su Kim, Yoshiki Koizumi, Shinji Nakaoka, Keisuke Ejima, Naoko Misawa, Yoshio Koyanagi, Kei Sato, Shingo Iwami
Journal of Theoretical Biology, 498, 110295, 110295, Elsevier BV, Aug. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, APOBEC3 proteins inhibit human immunodeficiency virus (HIV)-1 infection by independently impairing viral reverse transcription and inducing G-to-A mutations in viral DNA. An HIV-1-encoded protein, viral infectivity factor (Vif), can counteract these antiviral activities of APOBEC3 proteins. Although previous studies using in vitro cell culture systems have revealed the molecular mechanisms of the antiviral action of APOBEC3 proteins and their antagonism by Vif, it remains unclear how APOBEC3 proteins affect the kinetics of HIV-1 replication in vivo. Here we quantified the time-series of viral load datasets from humanized mice infected with HIV-1 variants in the presence of APOBEC3F, APOBEC3G, or both APOBEC3F/G using a simple mathematical model that accounted for inter-individual variability. Through experimental and mathematical investigation, we formulated and calculated the total antiviral activity of APOBEC3F and APOBEC3G based on the estimated initial growth rates of viral loads in vivo. Interestingly, we quantitatively demonstrated that compared with APOBEC3G, the antiviral activity of APOBEC3F was widely distributed but skewed toward lower activity, although their mean values were similar. We concluded that APOBEC3G markedly and robustly restricted the initial stages of viral growth in vivo. This is the first report to quantitatively elucidate how APOBEC3F and APOBEC3G differ in their anti-HIV-1 modes in vivo. - Should a viral genome stay in the host cell or leave? A quantitative dynamics study of how hepatitis C virus deals with this dilemma
Shoya Iwanami, Kosaku Kitagawa, Hirofumi Ohashi, Yusuke Asai, Kaho Shionoya, Wakana Saso, Kazane Nishioka, Hisashi Inaba, Shinji Nakaoka, Takaji Wakita, Odo Diekmann, Shingo Iwami, Koichi Watashi
PLOS Biology, 18, 7, e3000562, e3000562, Public Library of Science (PLoS), 30 Jul. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Virus proliferation involves gene replication inside infected cells and transmission to new target cells. Once positive-strand RNA virus has infected a cell, the viral genome serves as a template for copying ("stay-strategy") or is packaged into a progeny virion that will be released extracellularly ("leave-strategy"). The balance between genome replication and virion release determines virus production and transmission efficacy. The ensuing trade-off has not yet been well characterized. In this study, we use hepatitis C virus (HCV) as a model system to study the balance of the two strategies. Combining viral infection cell culture assays with mathematical modeling, we characterize the dynamics of two different HCV strains (JFH-1, a clinical isolate, and Jc1-n, a laboratory strain), which have different viral release characteristics. We found that 0.63% and 1.70% of JFH-1 and Jc1-n intracellular viral RNAs, respectively, are used for producing and releasing progeny virions. Analysis of the Malthusian parameter of the HCV genome (i.e., initial proliferation rate) and the number of de novo infections (i.e., initial transmissibility) suggests that the leave-strategy provides a higher level of initial transmission for Jc1-n, whereas, in contrast, the stay-strategy provides a higher initial proliferation rate for JFH-1. Thus, theoretical-experimental analysis of viral dynamics enables us to better understand the proliferation strategies of viruses, which contributes to the efficient control of virus transmission. Ours is the first study to analyze the stay-leave trade-off during the viral life cycle and the significance of the replication-release switching mechanism for viral proliferation. - Multiomics Investigation Revealing the Characteristics of HIV-1-Infected Cells In Vivo.
Hirofumi Aso, Shumpei Nagaoka, Eiryo Kawakami, Jumpei Ito, Saiful Islam, Benjy Jek Yang Tan, Shinji Nakaoka, Koichi Ashizaki, Katsuyuki Shiroguchi, Yutaka Suzuki, Yorifumi Satou, Yoshio Koyanagi, Kei Sato
Cell reports, 32, 2, 107887, 107887, 14 Jul. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, For eradication of HIV-1 infection, it is important to elucidate the detailed features and heterogeneity of HIV-1-infected cells in vivo. To reveal multiple characteristics of HIV-1-producing cells in vivo, we use a hematopoietic-stem-cell-transplanted humanized mouse model infected with GFP-encoding replication-competent HIV-1. We perform multiomics experiments using recently developed technology to identify the features of HIV-1-infected cells. Genome-wide HIV-1 integration-site analysis reveals that productive HIV-1 infection tends to occur in cells with viral integration into transcriptionally active genomic regions. Bulk transcriptome analysis reveals that a high level of viral mRNA is transcribed in HIV-1-infected cells. Moreover, single-cell transcriptome analysis shows the heterogeneity of HIV-1-infected cells, including CXCL13high cells and a subpopulation with low expression of interferon-stimulated genes, which can contribute to efficient viral spread in vivo. Our findings describe multiple characteristics of HIV-1-producing cells in vivo, which could provide clues for the development of an HIV-1 cure. - 桑葉摂取によるα-defensinと腸内細菌叢の経時変化に対する統計解析
子安 惟, 中岡 慎治, 菊池 摩仁, 中村 公則, 綾部 時芳
腸内細菌学雑誌, 34, 2, 123, 123, (公財)腸内細菌学会, Apr. 2020
Japanese - An information and statistical analysis pipeline for microbial metagenomic sequencing data
Shinji Nakaoka, Keisuke H. Ota
Handbook of Statistics, Elsevier B.V., 2020
English, In book - Information and Statistical Analysis Pipeline for High-Throughput RNA Sequencing Data.
Shinji Nakaoka, Keita Matsuyama
Methods in molecular biology (Clifton, N.J.), 2109, 199, 208, 2020, [International Magazine]
English, Scientific journal, Applications of RNA sequencing have been wide-spreading in various subfields of life science. Construction of information and statistical analysis pipeline is indispensable to process raw RNA sequencing (RNA-seq) data generated by next-generation sequencers in order to extract biological implications. In this chapter, we introduce a common pipeline for RNA-seq data. A collection of notes on related advanced topics will be useful when conducting information and statistical analysis in practice. - A mathematical model for dynamics of soluble form of DNAM-1 as a biomarker for graft-versus-host disease.
Yuki Goshima, Shinji Nakaoka, Kazuteru Ohashi, Hisashi Sakamaki, Kazuko Shibuya, Akira Shibuya
PloS one, 15, 2, e0228508, 2020, [International Magazine]
English, Scientific journal, DNAM-1 (CD226) is an activating immunoreceptor expressed on T cells and NK cells and involved in the pathogenesis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We previously reported that a soluble form of DNAM-1 (sDNAM-1) is generated by shedding from activated T cells. Moreover, higher serum levels of sDNAM-1 in patients before allo-HSCT is a predictive biomarker for the development of aGVHD based on the retrospective univariate and multivariate analyses in allo-HSCT patients. However, it remains unclear how the serum levels of sDNAM-1 are regulated after allo-HSCT and whether they are associated with the development of aGVHD. Here, we constructed a mathematical model to assess the dynamics of sDNAM-1 after allo-HSCT by assuming that there are three types of sDNAM-1 (the first and the second were from alloreactive and non-alloreactive donor lymphocytes, respectively, and the third from recipient lymphocytes). Our mathematical model fitted well to the data set of sDNAM-1 in patients (n = 67) who had undergone allo-HSCT and suggest that the high proportion of the first type of sDNAM-1 to the total of the first and second types is associated with high risk of the development of severe aGVHD. Thus, sDNAM-1 after allo-HSCT can be a biomarker for the development of aGVHD. - The Rules of Human T Cell Fate in vivo.
Pedro Costa Del Amo, Bisrat Debebe, Milad Razavi-Mohseni, Shinji Nakaoka, Andrew Worth, Diana Wallace, Peter Beverley, Derek Macallan, Becca Asquith
Frontiers in immunology, 11, 573, 573, 2020, [International Magazine]
English, Scientific journal, The processes governing lymphocyte fate (division, differentiation, and death), are typically assumed to be independent of cell age. This assumption has been challenged by a series of elegant studies which clearly show that, for murine cells in vitro, lymphocyte fate is age-dependent and that younger cells (i.e., cells which have recently divided) are less likely to divide or die. Here we investigate whether the same rules determine human T cell fate in vivo. We combined data from in vivo stable isotope labeling in healthy humans with stochastic, agent-based mathematical modeling. We show firstly that the choice of model paradigm has a large impact on parameter estimates obtained using stable isotope labeling i.e., different models fitted to the same data can yield very different estimates of T cell lifespan. Secondly, we found no evidence in humans in vivo to support the model in which younger T cells are less likely to divide or die. This age-dependent model never provided the best description of isotope labeling; this was true for naïve and memory, CD4+ and CD8+ T cells. Furthermore, this age-dependent model also failed to predict an independent data set in which the link between division and death was explored using Annexin V and deuterated glucose. In contrast, the age-independent model provided the best description of both naïve and memory T cell dynamics and was also able to predict the independent dataset. - Revealing uninfected and infected target cell dynamics from peripheral blood data in highly and less pathogenic simian/human immunodeficiency virus infected Rhesus macaque.
Akane Hara, Shoya Iwanami, Yusuke Ito, Tomoyuki Miura, Shinji Nakaoka, Shingo Iwami
Journal of theoretical biology, 479, 29, 36, 21 Oct. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Since chimeric simian and human immunodeficiency viruses (SHIVs) used here, that is, SHIV-#64 and -KS661 utilize both CCR5 and CXCR4 chemokine receptors, they have broad target cell properties. A highly pathogenic SHIV strain, SHIV-KS661, causes an infection that systemically depletes the CD4+ T cells of Rhesus macaques, while a less pathogenic strain, SHIV-#64, does not cause severe symptoms in the macaques. In our previous studies, we established in vitro quantification system for virus infection dynamics, and concluded that SHIV-KS661 effectively produces infectious virions compared with SHIV-#64 in the HSC-F cell culture. However, in vivo dynamics of SHIV infection have not been well understood. To quantify SHIV-#64 and -KS661 infection dynamics in Rhesus macaques, we developed a novel approach and analyzed total CD4+ T cells and viral load in peripheral blood, and reproduced the expected dynamics for the uninfected and infected CD4+ T cells in silico. Using our previous cell culture experimental datasets, we revealed that an infection rate constant is different between SHIV-#64 and -KS661, but the viral production rate and the death rate are similar for the both strains. Thus, here, we assumed these relations in our in vivo data and carried out the data fitting. We performed Bayesian estimation for the whole dataset using MCMC sampling, and simultaneously fitted our novel model to total CD4+ T cells and viral load of SHIV-#64 and -KS661 infection. Our analyses explained that the Malthusian parameter (i.e., fitness of virus infection) and the basic reproduction number (i.e., potential of virus infection) for SHIV-KS661 are significantly higher than those of SHIV-#64. In addition, we demonstrated that the number of uninfected CD4+ T cells in SHIV-KS661 infected Rhesus macaques decreases to the significantly lower value than that before the inoculation several days earlier compared with SHIV-#64 infection. Taken together, the differences between SHIV-#64 and -KS661 infection before the peak viral load might determine the subsequent destiny, that is, whether the systemic CD4+ T cell depletion occurs or the host immune response develop. - T-Cell mediated adaptive immunity and antibody-dependent enhancement in secondary dengue infection.
Sourav Kumar Sasmal, Yasuhiro Takeuchi, Shinji Nakaoka
Journal of theoretical biology, 470, 50, 63, 07 Jun. 2019, [International Magazine]
English, Scientific journal, Dengue infection results in a significant number of deaths, mostly in the tropical and subtropical regions across the world. Yet, despite the seriousness of this disease, vaccine, and antiviral drugs that could be employed in dengue treatment remain elusive. The desire to establish the factors determining the disease severity and the growing need for efficient drugs has prompted extensive research interest in within-host viral dynamics. However, very few mathematical models of within-host dengue dynamics pertaining to secondary dengue infection with another serotype are presently available. To address this gap in the pertinent literature, in this work, a secondary dengue infection model with T-cell mediated adaptive immunity and antibody-dependent enhancement was developed by considering the memory cell and heterogeneous antibody as the main factor. In particular, the explicit role of cytokines is considered for both virus and infected cell clearance, along with both extrinsic and intrinsic mechanisms for antibody-dependent enhancement. In case of secondary dengue infection, both the virus and homogeneous antibody production are enhanced due to the influence of memory cells remaining from the previous (primary) dengue infection. Owing to the high model sensitivity, it was possible to establish that, among antibody-dependent enhancement mechanisms, the increased virus replication inside the infected cell, which increases the overall virus burst size, exerts the maximum effect on disease severity during secondary infection. Moreover, the role of initial memory cell concentrations and half-saturation constant in the secretion of memory cell in the disease severity was studied. The obtained results concur with the clinical observations and may be helpful in further research on antibody-dependent enhancements aimed at producing schemes relevant for the dengue vaccine design and development. - Mathematical Analysis of a Transformed ODE from a PDE Multiscale Model of Hepatitis C Virus Infection
Kosaku Kitagawa, Toshikazu Kuniya, Shinji Nakaoka, Yusuke Asai, Koichi Watashi, Shingo Iwami
Bulletin of Mathematical Biology, 81, 5, 1427, 1441, Springer Science and Business Media LLC, May 2019, [Peer-reviewed]
Scientific journal - Calculation of final size for vector-transmitted epidemic model.
Yu Tsubouchi, Yasuhiro Takeuchi, Shinji Nakaoka
Mathematical biosciences and engineering : MBE, 16, 4, 2219, 2232, 15 Mar. 2019, [International Magazine]
English, Scientific journal, Calculation of final size of an epidemic model offers a useful estimation for the impact of an epidemic. Despite its usefulness, the majority of practical applications focuses on the classical Kermack McKendrick model for final size calculation. Estimation of final size for different types of epidemics such as vector-transmitted infection is a forthcoming target. In this paper, we derive an explicit form of a final size equation for a vector-transmitted epidemic model. Numerical calculation of a final size equation revealed the existence of a threshold curve which separates a region into two distinct bistable sub-regions if infection induced death is present. In other words, an epidemic outcome can be qualitatively different depending on the initial state of an epidemic. - A mathematical model of multiple delayed feedback control system of the gut microbiota—Antibiotics injection controlled by measured metagenomic data
Yueping Dong, Yasuhiro Takeuchi, Shinji Nakaoka
Nonlinear Analysis: Real World Applications, 43, 1, 17, 01 Oct. 2018, [Peer-reviewed]
English, Scientific journal - Publisher Correction: Core microbiomes for sustainable agroecosystems.
Toju H, Peay KG, Yamamichi M, Narisawa K, Hiruma K, Naito K, Fukuda S, Ushio M, Nakaoka S, Onoda Y, Yoshida K, Schlaeppi K, Bai Y, Sugiura R, Ichihashi Y, Minamisawa K, Kiers ET
Nature plants, 4, 9, 733, 733, Sep. 2018, [Peer-reviewed], [International Magazine]
English, Owing to a technical error, this Perspective was originally published without its received and accepted dates; the dates "Received: 31 December 2017; Accepted: 23 March 2018" have now been included in all versions. - A PDE multiscale model of hepatitis C virus infection can be transformed to a system of ODEs
Kosaku Kitagawa, Shinji Nakaoka, Yusuke Asai, Koichi Watashi, Shingo Iwami
Journal of Theoretical Biology, 448, 80, 85, Elsevier BV, Jul. 2018, [Peer-reviewed]
Scientific journal - Delayed feedback induced complex dynamics in an Escherichia coli and Tetrahymena system
Yueping Dong, Moitri Sen, Malay Banerjee, Yasuhiro Takeuchi, Shinji Nakaoka
Nonlinear Dynamics, 1, 20, Springer Netherlands, 25 Jun. 2018, [Peer-reviewed]
English, Scientific journal - Core microbiomes for sustainable agroecosystems.
Toju H, Peay KG, Yamamichi M, Narisawa K, Hiruma K, Naito K, Fukuda S, Ushio M, Nakaoka S, Onoda Y, Yoshida K, Schlaeppi K, Bai Y, Sugiura R, Ichihashi Y, Minamisawa K, Kiers ET
Nature plants, 4, 5, 247, 257, May 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal - Sporadic on/off switching of HTLV-1 Tax expression is crucial to maintain the whole population of virus-induced leukemic cells
Mohamed Mahgoub, Jun-ichirou Yasunaga, Shingo Iwami, Shinji Nakaoka, Yoshiki Koizumi, Kazuya Shimura, Masao Matsuoka
Proceedings of the National Academy of Sciences, 115, 6, E1269, E1278, 06 Feb. 2018, [Peer-reviewed]
Scientific journal - The CCR4-NOT deadenylase complex controls Atg7-dependent cell death and heart function.
Tomokazu Yamaguchi, Takashi Suzuki, Teruki Sato, Akinori Takahashi, Hiroyuki Watanabe, Ayumi Kadowaki, Miyuki Natsui, Hideaki Inagaki, Satoko Arakawa, Shinji Nakaoka, Yukio Koizumi, Shinsuke Seki, Shungo Adachi, Akira Fukao, Toshinobu Fujiwara, Tohru Natsume, Akinori Kimura, Masaaki Komatsu, Shigeomi Shimizu, Hiroshi Ito, Yutaka Suzuki, Josef M Penninger, Tadashi Yamamoto, Yumiko Imai, Keiji Kuba
Science signaling, 11, 516, 06 Feb. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal - Human-Specific Adaptations in Vpu Conferring Anti-tetherin Activity Are Critical for Efficient Early HIV-1 Replication In Vivo
Eri Yamada, Shinji Nakaoka, Lukas Klein, Elisabeth Reith, Simon Langer, Kristina Hopfensperger, Shingo Iwami, Gideon Schreiber, Frank Kirchhoff, Yoshio Koyanagi, Daniel Sauter, Kei Sato
Cell Host and Microbe, 23, 1, 110, 120.e7, 10 Jan. 2018, [Peer-reviewed]
English, Scientific journal - Erratum to: Daphnia revisited: local stability and bifurcation theory for physiologically structured population models explained by way of an example (Journal of Mathematical Biology, (2010), 61, 2, (277-318), 10.1007/s00285-009-0299-y)
Odo Diekmann, Mats Gyllenberg, J. A.J. Metz, Shinji Nakaoka, Andre M. de Roos
Journal of Mathematical Biology, 61, 2, 277, 318, Springer Verlag, 01 Jul. 2017, [Peer-reviewed]
English, Scientific journal - Daphnia revisited: local stability and bifurcation theory for physiologically structured population models explained by way of an example (vol 61, pg 277, 2010)
Odo Diekmann, Mats Gyllenberg, J. A. J. Metz, Shinji Nakaoka, Andre M. de Roos
JOURNAL OF MATHEMATICAL BIOLOGY, 75, 1, 259, 261, Jul. 2017, [Peer-reviewed]
English - Number of infection events per cell during HIV-1 cell-free infection
Yusuke Ito, Azaria Remion, Alexandra Tauzin, Keisuke Ejima, Shinji Nakaoka, Yoh Iwasa, Shingo Iwami, Fabrizio Mammano
SCIENTIFIC REPORTS, 7, 1, 6559, Jul. 2017, [Peer-reviewed]
English, Scientific journal - HIV-1 competition experiments in humanized mice show that APOBEC3H imposes selective pressure and promotes virus adaptation
Yusuke Nakano, Naoko Misawa, Guillermo Juarez-Fernandez, Miyu Moriwaki, Shinji Nakaoka, Takaaki Funo, Eri Yamada, Andrew Soper, Rokusuke Yoshikawa, Diako Ebrahimi, Yuuya Tachiki, Shingo Iwami, Reuben S. Harris, Yoshio Koyanagi, Kei Sato
PLOS PATHOGENS, 13, 5, e1006348, May 2017, [Peer-reviewed]
English, Scientific journal - HIV-1 competition experiments in humanized mice show that APOBEC3H imposes selective pressure and promotes virus adaptation
Yusuke Nakano, Naoko Misawa, Guillermo Juarez-Fernandez, Miyu Moriwaki, Shinji Nakaoka, Takaaki Funo, Eri Yamada, Andrew Soper, Rokusuke Yoshikawa, Diako Ebrahimi, Yuuya Tachiki, Shingo Iwami, Reuben S. Harris, Yoshio Koyanagi, Kei Sato
PLOS PATHOGENS, 13, 5, e1006606, May 2017, [Peer-reviewed]
English, Scientific journal - A highly pathogenic simian/human immunodeficiency virus effectively produces infectious virions compared with a less pathogenic virus in cell culture
Shoya Iwanami, Yusuke Kakizoe, Satoru Morita, Tomoyuki Miura, Shinji Nakaoka, Shingo Iwami
THEORETICAL BIOLOGY AND MEDICAL MODELLING, 14, 1, 9, Apr. 2017, [Peer-reviewed]
English, Scientific journal - Modelling Ebola virus dynamics: Implications for therapy
Alexey Martyushev, Shinji Nakaoka, Kei Sato, Takeshi Noda, Shingo Iwami
ANTIVIRAL RESEARCH, 135, 62, 73, Nov. 2016, [Peer-reviewed]
English, Scientific journal - Chronic Inflammation in the Epidermis: A Mathematical Model
Shinji Nakaoka, Sota Kuwahara, Chang Hyeong Lee, Hyejin Jeon, Junho Lee, Yasuhiro Takeuchi, Yangjin Kim
APPLIED SCIENCES-BASEL, 6, 9, Sep. 2016, [Peer-reviewed]
English, Scientific journal - Hyperactivation of JAK1 tyrosine kinase induces stepwise, progressive pruritic dermatitis
Takuwa Yasuda, Toshiyuki Fukada, Keigo Nishida, Manabu Nakayama, Masashi Matsuda, Ikuo Miura, Teruki Dainichi, Shinji Fukuda, Kenji Kabashima, Shinji Nakaoka, Bum-Ho Bin, Masato Kubo, Hiroshi Ohno, Takanori Hasegawa, Osamu Ohara, Haruhiko Koseki, Shigeharu Wakana, Hisahiro Yoshida
JOURNAL OF CLINICAL INVESTIGATION, 126, 6, 2064, 2076, Jun. 2016, [Peer-reviewed]
English, Scientific journal - Weighted enrichment method for prediction of transcription regulators from transcriptome and global chromatin immunoprecipitation data
Eiryo Kawakami, Shinji Nakaoka, Tazro Ohta, Hiroaki Kitano
NUCLEIC ACIDS RESEARCH, 44, 11, 5010, 5021, Jun. 2016, [Peer-reviewed]
English, Scientific journal - New algorithm for constructing area-based index with geographical heterogeneities and variable selection: An application to gastric cancer screening
Daisuke Yoneoka, Eiko Saito, Shinji Nakaoka
SCIENTIFIC REPORTS, 6, 26582, May 2016, [Peer-reviewed]
English, Scientific journal - Quantifying the effect of Vpu on the promotion of HIV-1 replication in the humanized mouse model
Hiroki Ikeda, Shinji Nakaoka, Rob J. de Boer, Satoru Morita, Naoko Misawa, Yoshio Koyanagi, Kazuyuki Aihara, Kei Sato, Shingo Iwami
RETROVIROLOGY, 13, 23, Apr. 2016, [Peer-reviewed]
English, Scientific journal - Dynamics of HIV infection in lymphoid tissue network
Shinji Nakaoka, Shingo Iwami, Kei Sato
JOURNAL OF MATHEMATICAL BIOLOGY, 72, 4, 909, 938, Mar. 2016, [Peer-reviewed]
English, Scientific journal - Mathematical modeling and analysis of combinational immune boost for tumor elimination
Naoki Nakada, Mizuho Nagata, Yasuhiro Takeuchi, Shinji Nakaoka
SYMPOSIUM ON BIOMATHEMATICS (SYMOMATH 2015), 1723, 2016, [Peer-reviewed]
English, International conference proceedings - Identifying determinants of heterogeneous transmission dynamics of the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea, 2015: a retrospective epidemiological analysis
Hiroshi Nishiura, Akira Endo, Masaya Saitoh, Ryo Kinoshita, Ryo Ueno, Shinji Nakaoka, Yuichiro Miyamatsu, Yueping Dong, Gerardo Chowell, Kenji Mizumoto
BMJ OPEN, 6, 2, e009936, 2016, [Peer-reviewed]
English, Scientific journal - Dynamical behavior of combinational immune boost against tumor
Mizuho Nagata, Yutaro Furuta, Yasuhiro Takeuchi, Shinji Nakaoka
JAPAN JOURNAL OF INDUSTRIAL AND APPLIED MATHEMATICS, 32, 3, 759, 770, Nov. 2015, [Peer-reviewed]
English, Scientific journal - Cell-to-cell infection by HIV contributes over half of virus infection
Shingo Iwami, Junko S. Takeuchi, Shinji Nakaoka, Fabrizio Mammano, Francois Clavel, Hisashi Inaba, Tomoko Kobayashi, Naoko Misawa, Kazuyuki Aihara, Yoshio Koyanagi, Kei Sato
ELIFE, 4, Oct. 2015, [Peer-reviewed]
English, Scientific journal - Insecticide applications to soil contribute to the development of Burkholderia mediating insecticide resistance in stinkbugs.
Tago, K, Kikuchi, Y, Nakaoka, S, Katsuyama, C, Hayatsu, M
Molecular Ecology, 24, 14, 3766, 3788, Jul. 2015, [Peer-reviewed]
English, Scientific journal - A conservation law for virus infection kinetics in vitro
Yusuke Kakizoe, Satoru Morita, Shinji Nakaoka, Yasuhiro Takeuchi, Kei Sato, Tomoyuki Miura, Catherine A. A. Beauchemin, Shingo Iwami
JOURNAL OF THEORETICAL BIOLOGY, 376, 39, 47, Jul. 2015, [Peer-reviewed]
English, Scientific journal - A method to determine the duration of the eclipse phase for in vitro infection with a highly pathogenic SHIV strain
Yusuke Kakizoe, Shinji Nakaoka, Catherine A. A. Beauchemin, Satoru Morita, Hiromi Mori, Tatsuhiko Igarashi, Kazuyuki Aihara, Tomoyuki Miura, Shingo Iwami
SCIENTIFIC REPORTS, 5, 10371, May 2015, [Peer-reviewed]
English, Scientific journal - Effect of eclipse phase on quantifying viral dynamics of acute HIV-1 infection in humanized mouse model
Hiroki Ikeda, Shinji Nakaoka, Kei Sato, Naoko Misawa, Yoshio Koyanagi, Shingo Iwami
Nonlinear Theory and Its Applications, IEICE, 6, 1, 47, 53, 2015, [Peer-reviewed]
Scientific journal - Mathematical analysis and classification of tumor immune dynamics in T cell transfer treatment
Nakaoka Shinji
IEICE NONLINEAR THEORY AND ITS APPLICATIONS, 6, 1, 54, 70, 2015, [Peer-reviewed]
English - DEMOGRAPHIC MODELING OF TRANSIENT AMPLIFYING CELL POPULATION GROWTH
Shinji Nakaoka, Hisashi Inaba
MATHEMATICAL BIOSCIENCES AND ENGINEERING, 11, 2, 363, 384, Apr. 2014, [Peer-reviewed]
English, Scientific journal - Cost-effective length and timing of school closure during an influenza pandemic depend on the severity
Hiroshi Nishiura, Keisuke Ejima, Kenji Mizumoto, Shinji Nakaoka, Hisashi Inaba, Seiya Imoto, Rui Yamaguchi, Masaya M. Saito
THEORETICAL BIOLOGY AND MEDICAL MODELLING, 11, 1, 5, Jan. 2014, [Peer-reviewed]
English, Scientific journal - Multiscale mathematical modeling and simulation of cellular dynamical process
Shinji Nakaoka
Methods in Molecular Biology, 1195, 269, 283, Humana Press Inc., 2014, [Peer-reviewed]
English, Scientific journal - Stochastic simulation of structured skin cell population dynamics
Shinji Nakaoka, Kazuyuki Aihara
JOURNAL OF MATHEMATICAL BIOLOGY, 66, 4-5, 807, 835, Mar. 2013, [Peer-reviewed]
English, Scientific journal - Mathematical study on kinetics of hematopoietic stem cells - theoretical conditions for successful transplantation
Shinji Nakaoka, Kazuyuki Aihara
JOURNAL OF BIOLOGICAL DYNAMICS, 6, 2, 836, 854, 2012, [Peer-reviewed]
English, Scientific journal - Daphnia revisited: local stability and bifurcation theory for physiologically structured population models explained by way of an example
Odo Diekmann, Mats Gyllenberg, J. A. J. Metz, Shinji Nakaoka, Andre M. de Roos
JOURNAL OF MATHEMATICAL BIOLOGY, 61, 2, 277, 318, Aug. 2010, [Peer-reviewed]
English, Scientific journal - Daphnia revisited: Local stability and bifurcation theory for physiologically structured population models explained by way of an example
Odo Diekmann, Mats Gyllenberg, J. A.J. Metz, Shinji Nakaoka, André M. de Roos
Journal of Mathematical Biology, 75, 1, 259, 261, Springer Verlag, 01 Jul. 2010, [Peer-reviewed]
English, Scientific journal - Immune impairment in HIV infection: Existence of risky and immunodeficiency thresholds
Shingo Iwami, Tomoyuki Miura, Shinji Nakaoka, Yasuhiro Takeuchi
JOURNAL OF THEORETICAL BIOLOGY, 260, 4, 490, 501, Oct. 2009, [Peer-reviewed]
English, Scientific journal - Effect of parental care and aggregation on population dynamics
Shinji Nakaoka, Wendi Wang, Yasuhiro Takeuchi
JOURNAL OF THEORETICAL BIOLOGY, 260, 1, 161, 171, Sep. 2009, [Peer-reviewed]
English, Scientific journal - A geographical spread of vaccine-resistance in avian influenza epidemics
Shingo Iwami, Yasuhiro Takeuchi, Xianning Liu, Shinji Nakaoka
JOURNAL OF THEORETICAL BIOLOGY, 259, 2, 219, 228, Jul. 2009, [Peer-reviewed]
English, Scientific journal - Dynamical Adaptation of Parental Care
Yasuhiro Takeuchi, Wendi Wang, Shinji Nakaoka, Shingo Iwami
BULLETIN OF MATHEMATICAL BIOLOGY, 71, 4, 931, 951, May 2009, [Peer-reviewed]
English, Scientific journal - Immune impairment thresholds in HIV infection
Shingo Iwami, Shinji Nakaoka, Yasuhiro Takeuchi, Yoshiharu Miura, Tomoyuki Miura
IMMUNOLOGY LETTERS, 123, 2, 149, 154, Apr. 2009, [Peer-reviewed]
English, Scientific journal - Complementary cooperation between two syntrophic bacteria in pesticide degradation
Chie Katsuyama, Shinji Nakaoka, Yasuhiro Takeuchi, Kanako Tago, Masahito Hayatsu, Kenji Kato
JOURNAL OF THEORETICAL BIOLOGY, 256, 4, 644, 654, Feb. 2009, [Peer-reviewed]
English, Scientific journal - Invest conflicts of adult predators
Wendi Wang, Shinji Nakaoka, Yasuhiro Takeuchi
JOURNAL OF THEORETICAL BIOLOGY, 253, 1, 12, 23, Jul. 2008, [Peer-reviewed]
English, Scientific journal - Mathematical analysis of a HIV model with frequency dependence and viral diversity
Shingo Iwami, Shinji Nakaoka, Yasuhiro Takeuchi
MATHEMATICAL BIOSCIENCES AND ENGINEERING, 5, 3, 457, 476, Jul. 2008, [Peer-reviewed]
English, Scientific journal - Viral diversity limits immune diversity in asymptomatic phase of HIV infection
Shingo Iwami, Shinji Nakaoka, Yasuhiro Takeuchi
THEORETICAL POPULATION BIOLOGY, 73, 3, 332, 341, May 2008, [Peer-reviewed]
English, Scientific journal - Two types of coexistence in cross-feeding microbial consortia
Shinji Nakaoka, Yasuhiro Takeuchi
COLLECTIVE DYNAMICS: TOPICS ON COMPETITION AND COOPERATION IN THE BIOSCIENCES, 1028, 233, +, 2008, [Peer-reviewed]
English, International conference proceedings - Frequency dependence and viral diversity imply chaos in an HIV model
Shingo Iwami, Shinji Nakaoka, Yasuhiro Takeuchi
PHYSICA D-NONLINEAR PHENOMENA, 223, 2, 222, 228, Nov. 2006, [Peer-reviewed]
English, Scientific journal - Prey-predator system with parental care for predators
Wendi Wang, Yasuhiro Takeuchi, Yasuhisa Saito, Shinji Nakaoka
JOURNAL OF THEORETICAL BIOLOGY, 241, 3, 451, 458, Aug. 2006, [Peer-reviewed]
English, Scientific journal - Competition in chemostat-type equations with two habitats
Shinji Nakaoka, Yasuhiro Takeuchi
MATHEMATICAL BIOSCIENCES, 201, 1-2, 157, 171, May 2006, [Peer-reviewed]
English, Scientific journal
Other Activities and Achievements
- Effect of shapes of activation functions on predictability in the echo state network (複雑コミュニケーションサイエンス)
張 瀚天, 中岡 慎治, 安東 弘泰, 電子情報通信学会技術研究報告 = IEICE technical report : 信学技報, 119, 157, 27, 30, 01 Aug. 2019
電子情報通信学会, English - 細菌群集データから相互作用ネットワークを推定する手法の活用 (複雑コミュニケーションサイエンス)
中岡 慎治, 鈴木 憲幸, 竹内 康博, 電子情報通信学会技術研究報告 = IEICE technical report : 信学技報, 119, 157, 23, 25, 01 Aug. 2019
電子情報通信学会, Japanese - Quantification of Hepatitis B Virus infection dynamics in cell culture model
Kakizoe Yusuke, Iwamoto Masashi, Nakaoka Shinji, Watashi Koichi, Iwami Shingo, RIMS Kokyuroku, 2087, 71, 76, Aug. 2018
Research Institute for Mathematical Sciences, Kyoto University, Japanese - Big-data analysis of allergy associations with gut microbiota
HARA Akane, NAKAOKA Shinji, AIHARA Kazuyuki, SEISAN KENKYU, 70, 3, 141, 144, 2018Close association between intestinal microbiota and the immune system suggests possibility of developing a novel treatment method for allergy by modulating intestinal microbiota. Although time-series data with sufficient length are required for microbiota modulation, no such datasets are found which match the requirement. In this study, we apply and examine a new method to reconstruct a pseudo-temporal path of allergy development from non-time-series samples reflecting various individual states in the process of allergy development. We aim to refine this method to provide a data-driven intervention strategy for prevention of allergy.
, Institute of Industrial Science The University of Tokyo, English - HIV-1侵入機構の定量化 (第13回生物数学の理論とその応用 : 連続および離散モデルのモデリングと解析)
柿添 友輔, 中岡 慎治, 岩見 真吾, 数理解析研究所講究録, 2043, 81, 86, Sep. 2017
京都大学数理解析研究所, Japanese - マルチスケールモデルを用いたC型肝炎ウイルスの感染動態の記述 (第13回生物数学の理論とその応用 : 連続および離散モデルのモデリングと解析)
北川 耕咲, 中岡 慎治, 浅井 雄介, 岩見 真吾, 数理解析研究所講究録, 2043, 109, 115, Sep. 2017
京都大学数理解析研究所, Japanese - New deprivation index for large scale cancer study with geographical heterogeneity
YONEOKA Daisuke, SAITO Eiko, NAKAOKA Shinji, 日本疫学会学術総会講演集(Web), 27th, 2017 - Comparison of two different formulations of multiscale models for HCV infection
KITAGAWA Kousaku, NAKAOKA Shinji, ASAI Yusuke, AIHARA Kazuyuki, IWAMI Shingo, SEISAN KENKYU, 69, 3, 151, 153, 2017
<p>A mathematical model of Hepatitis C Virus （HCV） dynamics with RNA replication under antiviral therapy was constructed by a set of partial differential equations （PDEs）. In previous works, they solved the model as ordinary differential equations（ ODEs） under the assumption of no de-novo infection and its analytical solution was used to describe the dynamics. However, the previous model by this approach has a limitation when it is applied to clinical data. Therefore, we developed a new mathematical model which is mathematically equivalent to PDE and compared the performance of our approach to the previous PDE model.</p>, 東京大学生産技術研究所, English - パッチ感染モデルを用いた基本・状態別再生産数の違いの検証 (実領域における常微分方程式の定性的研究)
石塚 信行, 竹内 康博, 中岡 慎治, 数理解析研究所講究録, 1993, 79, 84, Apr. 2016
京都大学数理解析研究所, Japanese - 個体および集団ベースGillespieアルゴリズムの相互検証 (第11回生物数学の理論とその応用 : RIMS研究集会報告集)
中岡 慎治, 数理解析研究所講究録, 1937, 163, 170, Apr. 2015
京都大学数理解析研究所, Japanese - Comparison of Numerical Simulation Methods for HIV Infection Dynamics Model in Lymphatic Network(
Theory of Mathematical Models and Control for Infectious Diseases)
NAKAOKA Shinji, IWAMI Shingo, SATO Kei, SYSTEMS, CONTROL AND INFORMATION, 59, 12, 452, 457, 2015
THE INSTITUTE OF SYSTEMS, CONTROL AND INFORMATION ENGINEERS, Japanese - Quantification of viral infection dynamics with hybrid dynamical model
KAKIZOE Yusuke, NAKAOKA Shinji, AIHARA Kazuyuki, IWAMI Shingo, SEISAN KENKYU, 67, 3, 275, 279, 2015
Mathematical modeling has contributed to quantitative understanding of viral infections. The basic model,<b> </b><i>T'</i>(<i>t</i>)<i>=</i>－<i>βT</i>(<i>t</i>)<i>V</i>(<i>t</i>)<i>, I'</i>(<i>t</i>)<i>=βT</i>(<i>t</i>)<i>V</i>(<i>t</i>)－<i>δI</i>(<i>t</i>)<i> </i>and <i>V'</i>(<i>t</i>)<i>=pI</i>(<i>t</i>)－<i>cV</i>(<i>t</i>), has been analyzed which clinical or experimental data sets for many kinds of virus infections so far. However, in the basic model, we implicitly assume that punctual removal of cells and virions due to experimental sampling in cell cultures is described by an exponentially decay. However, the removal of cells and virions is performed instantaneously in viral infection experiments. Therefore, there might be differences among estimated parameters when we use the basic model or an explicit model including the punctual removal. Here, we constructed a hybrid dynamical model which describes the punctual removal by piecewise continuous function to the basic model. We analyzed time course of experimental data for SHIV-KS661 and SHIV-#64 infection <i>in vitro</i> by the basic model and the hybrid dynamical model, and compared the estimated parameters. Interestingly, we found that these two models give similar parameter estimations, and well capture the experimental virus infections. Our results provide a validation of the exponential decay assumption for the punctual removal in terms of parameter estimations., Institute of Industrial Science The University of Tokyo, Japanese - 個体ベースのGillespieアルゴリズム解説 (第10回生物数学の理論とその応用 : RIMS研究集会報告集)
中岡 慎治, 数理解析研究所講究録, 1917, 21, 28, Sep. 2014
京都大学数理解析研究所, Japanese - ディレイ方程式による短期細胞増殖過程の定式化 (第9回生物数学の理論とその応用 : RIMS研究集会報告集)
中岡 慎治, 数理解析研究所講究録, 1853, 19, 26, Oct. 2013
京都大学数理解析研究所, Japanese - Mathematical modeling for the self-organization of cells
KOJIMA Nobuhiko, OGATA Yuka, NAKAOKA Shinji, SAKAI Yasuyuki, SEISAN KENKYU, 65, 3, 337, 342, 2013
In order to fabricate three-dimensionally reconstituted tissues, it is indispensable to use pattern formation of cells using interaction of mutual cells. However, it is unclear that what kind of mechanisms are included such self-organization. In this report, we aimed to establish a mathematical model that can emulate the behavior of cells computationally. This trial will be able to control and regulate the pattern formation., Institute of Industrial Science The University of Tokyo, Japanese - Simulation study of helper T cell growth and differentiation
NAKAOKA Shinji, AIHARA Kazuyuki, SEISAN KENKYU, 65, 3, 273, 280, 2013
Helper T cells emerge from naive T cells via lineage commitment. Helper T cells play a pivotal role in adaptive immune response to remove antigen. Most of previous mathematical studies only consider either population dynamics of T cell clonal expansion or intracellular change of gene expression for transcription factors. In the present paper, on the other hand, we construct an individual based model which describes intra- and inter-cellular dynamics of T cell lineage commitment, and then carry out stochastic simulations to investigate how balance between two specific subsets is maintained. The method presented here can be effectively utilized to trace dynamics of a cell population such as immune cells which generically change their behavioral pattern during development., Institute of Industrial Science The University of Tokyo, Japanese - Mathematical modeling study on hematopoietic stem cells
NAKAOKA Shinji, AIHARA Kazuyuki, SEISAN KENKYU, 63, 3, 358, 369, 2011
We review recent progress in mathematical study on hematopoietic stem cells. This review paper deals with theoretical investigations for two major issues on basic and clinical hematology: “disorder of homeostasis in hematopoiesis” and “transplantation of hematopoietic stem cells”. Several mathematical models are introduced to describe self-renewal and differentiation of hematopoietic stem cells. Finally, future potential applications of mathematical study to regenerative medicine and cancer treatment are discussed.<br>, Institute of Industrial Science The University of Tokyo, Japanese - 細胞傷害性T細胞による感染細胞除去率の推定 (第6回生物数学の理論とその応用--RIMS研究集会報告集)
中岡 慎治, 合原 一幸, 数理解析研究所講究録, 1704, 40, 46, Aug. 2010
京都大学数理解析研究所, Japanese - Mathematical modeling study on immune systems
NAKAOKA Shinji, TAKI Hisao, AIHARA Kazuyuki, SEISAN KENKYU, 62, 3, 235, 240, 2010
In this review paper, we introduce recent progress in theoretical immunology, especially focusing on studies toward quantitative experiments for cell population growth and their mathematical models. We also show that, among mathematical models which have been independently developed by different authors, there exist similarities in terms of mathematical structure and underlying implicit assumptions., Institute of Industrial Science The University of Tokyo, Japanese - ポジティブフィードバックをもつ生物系モデルの解析 (関数方程式のダイナミクスと数理モデル--RIMS研究集会報告集)
中岡 慎治, 数理解析研究所講究録, 1637, 176, 188, Apr. 2009
京都大学数理解析研究所, Japanese - 個体の成長を考慮した個体群モデルの解析
中岡 慎治, 盛岡応用数学小研究集会報告集, 2008, 30, 43, 01 Mar. 2009
本稿では，ステージ構造をもつ資源消賢者系のダイナミクスに対する数理解析の結果を紹介する．消費者の個体に年齢構造を考慮し，繁殖可能性の有無によってその個体を区別する方程式系が対象である．未成熟個休の死亡率に時間遅れを伴った密度依存効果を考慮し，それによってダイナミクスがどう影響されるかを明らかにする．消費者が存続できるような状況を数学的に表現する一様パーシステンス，Allee効果と呼ばれるメカニズムによる消費者の絶滅という2つのキーワードに基づき，消費者の存続性と絶滅可能性を議論した．, 岩手大学人文社会科学部, Japanese - Occurrence of periodic oscillations mediated by programmed proliferation of CTLs (Theory of Biomathematics and its Applications IV)
Nakaoka Shinji, RIMS Kokyuroku, 1597, 19, 23, May 2008
Kyoto University, English - When do patients develop AIDS? (Theory of Biomathematics and its Applications IV)
Iwami Shingo, Nakaoka Shinji, Takeuchi Yasuhiro, RIMS Kokyuroku, 1597, 24, 26, May 2008
Kyoto University, English - Mathematical study on sharing metabolism (Workshops on "Pattern Formation Problems in Dissipative Systems" and "Mathematical Modeling and Analysis for Nonlinear Phenomena")
NAKAOKA Shinji, TAKEUCHI Yasuhiro, RIMS Kokyuroku Bessatsu, 3, 193, 205, Nov. 2007
Kyoto University, English - Steady state analysis for some delay equations(Functional Equations Based upon Phenomena)
Nakaoka Shinji, RIMS Kokyuroku, 1547, 34, 42, Apr. 2007
Kyoto University, English - Oscillations induced by size-structured populations with saturating food dependent reproduction rate(Theory of Biomathematics and its Applications III)
Nakaoka Shinji, RIMS Kokyuroku, 1551, 93, 98, Apr. 2007
Kyoto University, English - PA-40 Mathematical modeling and experimental analysis of syntrophic association in pesticide degradation(Symbiosis/Cell to cell interaction,Poster presentation A) :
Katsuyama Chie, Nakaoka Shinji, Takeuchi Yasuhiro, Tago Kanako, Hayatsu Masahito, Kato Kenji, 日本微生物生態学会講演要旨集, 23, 96, 96, 2007
日本微生物生態学会, English - Viral diversity in asymptomatic phase of HIV infection(Theory of Bio-Mathematics and Its Applications)
Iwami Shingo, Nakaoka Shinji, RIMS Kokyuroku, 1499, 37, 49, Jul. 2006
Kyoto University, English - Two species, one feeding on the other (Biomathematics Kyoto Summer School)
Nakaoka Shinji, RIMS Kokyuroku, 1448, 67, 81, Sep. 2005
Kyoto University, Japanese - Necessary condition for the coexistence of species in a periodic chemostat (Functional Equations and Complex Systems)
Nakaoka Shinji, Takeuchi Yasuhiro, RIMS Kokyuroku, 1445, 46, 55, Jul. 2005
Kyoto University, English - Balance Line in a Lotka-Volterra competition system (Theory of Bio-Mathematics and It's Applications)
Nakaoka Shinji, Takeuchi Yasuhiro, RIMS Kokyuroku, 1432, 23, 32, May 2005
Kyoto University, English - Stability Analysis for a physiological clock model with delayed negative feedback loop (Mathematical models and dynamics of functional equations)
Nakaoka Shinji, RIMS Kokyuroku, 1372, 51, 57, Apr. 2004
Kyoto University, English - Local Asymptotic Stability for a Lotka-Volterra System with Distributed Delays (Functional Equations in Mathematical Models)
Nakaoka Shinji, Hara Tadayuki, Matsunaga Hideaki, RIMS Kokyuroku, 1309, 84, 91, Feb. 2003
Kyoto University, Japanese
Books and other publications
- 進化のダイナミクス 生命の謎を解き明かす方程式
Martin A. Nowak, 中岡 慎治, 巌佐 庸, 竹内 康博, 佐藤 一憲
共立出版, 20 Feb. 2008, 4320056655, 352
Research Themes
- A novel dynamics analysis of marine plankton based on genetic information in the dissolved fraction of seawater
Core Research for Evolutional Science and Technology
Oct. 2023 - Mar. 2029
鈴木 光次, 中岡 慎一郎, 遠藤 寿, 中岡 慎治
Japan Science and Technology Agency, JST CREST, JPMJCR23J4 - Construction of state transition model based on energy landscape
Grants-in-Aid for Scientific Research
09 Jul. 2021 - 31 Mar. 2024
中岡 慎治
本年度では、細胞分化や発症の動的な遷移の軌跡を推定する手法の妥当性を検証するために必要なデータ解析を進め、結果として査読付研究論文を３編発表した。 研究論文 [1] では、授乳期における母子から5ヶ月間にわたって経時的に取得した腸内細菌叢データと代謝物の網羅的計測データ (NMRメタボロミクス) の時系列データ解析を行った。その結果、ビフィズス菌種の交代（Bifidobacterium breve から Bifidobacterium longum subsp. infantis）、糞便中の酢酸や酪酸などの代謝物も変動がみられることを明らかにした。
研究論文 [2] では、複雑な微生物および微生物・宿主間の相互作用を推定するため、数理モデルのシミュレーションから得られた微生物動態の擬似的時系列データを用いて、微生物相互作用ネットワークを推定する５つの手法について比較検討した。本研究課題と関連して、相互作用を検出する手法候補の１つを提案した。その結果、提案手法の有用性を確認することができた。
書籍のChapterとして寄稿した研究論文 [3] では、重要な疾患である発ガン過程に着目した解析を進めた。具体的には、ガン細胞がどのように増殖・進化して体内に存続するかを検討するため、ガン細胞集団の動態を記述した数理モデルをシミュレーションから得られたガン細胞動態の擬似的時系列データを用いて、細胞間相互作用を推定する手法の検討を行った。その結果、相互作用関係を推定する手法と発ガン進行パターンを記述した力学系の間に、興味深い関係性が得られることを見出した。
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Research (Exploratory), Hokkaido University, 21K19813 - Development of an integrated model for estimating emerging infectious diseases and a method for allocating medical resources by integrating mathematical science and healthcare administration
Grants-in-Aid for Scientific Research
09 Jul. 2021 - 31 Mar. 2024
佐藤 大介, 中岡 慎治, 川上 英良, 吉村 健佑, 藤田 卓仙
本研究は数理科学に基づくモデルを用いて新型コロナウイルス感染症の陽性者数および入院患者数等を推計し、公衆衛生学的介入やワクチン等による感染拡大防止政策が、どの対象や範囲に介入すれば最も効果的かつ医療需要に対する最適な医療資源を配置可能かを推計する数理モデルに基づく医療経済評価の手法を開発することである。
新型コロナウイルス感染症の陽性者数および入院患者数の把握は、感染拡大による急激な感染者増と都道府県および保健所設置市の人員不足や検査体制、情報収集方法の技術的課題等に加え、保健所が入力したデータは国の管理下に置かれ、入力した自治体が使用することが出来ず、研究利用として個票単位でのデータ収集が困難であった。そのため本研究では特定の都道府県に限定し、報道発表を通じて公表されている個票データを日別に集計することで、モデル分析に必要なデータを収集した。第６波以降はさらなる感染者数の増加により、公表資料においても集計値のみとされ個票でのデータ収集が不可能となった。これらの代替手法により、本年度においては第１波から第５波までの個票データをデータセットとして整理した。
いっぽうで、新型コロナウイルス感染症の陽性者等に関する情報の取り扱いに関する法的・倫理的課題（ELSI）については、特にIT技術を利用した感染症対策のELSI上の問題点についての課題を整理した。特にワクチン及び治療薬が存在しない段階の非製薬的介入（Nonpharmaceutical Interventions; NPIs）にIT技術を利活用する分類について、①隔離（措置入院、自宅療養、隔離）、②検疫（待機要請、停留）、③行動制限（緊急事態宣言、蔓延防止重点措置）、④リスク広報（政府公報）、⑤個人的防御（うがい、手洗い、マスク）の5類型を列挙し、公衆衛生上必要な個人情報を収集する場合の法的・倫理的課題を整理した。
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Research (Exploratory), Chiba University, 21K19629 - PHRを活用した機械学習モデルによる心血管病の重症化予防を目指した研究
科学研究費助成事業
01 Apr. 2021 - 31 Mar. 2024
横田 卓, 中岡 慎治, 中村 公則
わが国は超高齢社会を迎え、心血管病の患者数は増加の一途を辿っており、早急に患者本人が主体的にセルフモニタリングを行い疾病予防に取り組む「患者中心の医療 (patient-centered care)」 を実現する必要に迫られている。心血管病の予防・治療の基本は食事・運動をはじめとする生活習慣の是正であるが、在宅で取得可能なパーソナル・ヘルス・レコード (PHR) の活用が必要不可欠である。さらにCOVID-19感染拡大をきっかけにオンライン診療が広く推奨されるようになり、とりわけ情報通信技術 (ICT) を活用したPHRのニーズが高まっている。そこで我々は、在宅で取得するPHRを活用し適切なセルフケアの実践を促すスマートフォン対応セルフケアサポートアプリを開発した。本研究の目的は、このアプリで収集する血圧・体重・体脂肪率・体温・酸素飽和度・塩分摂取量・身体活動量・睡眠時間などのバイタルサインや食事・運動内容、さらには便を用いた腸内フローラ解析データなどの多様なPHRを活用し、機械学習モデルを用いて、心血管病の重症化予測を行うとともに重症化予防のための個々に最適な食事・運動療法を提案することである。
臨床試験『スマートフォンアプリを活用した統合型高血圧セルフケアサポートシステムの有効性の検証 (AppCare-HT Study)』については、2022年3月までに目標症例数 (360名) に達したため、募集を終了し、現在12か月間のフォローアップを実施中である。また、心不全患者を対象にした臨床試験についても研究実施中で、順次データ解析を進めている。
日本学術振興会, 基盤研究(C), 北海道大学, 21K08120 - Emerging infectious diseases of bees in Japan: integrated risk assessment for conservation
Grants-in-Aid for Scientific Research
01 Apr. 2020 - 31 Mar. 2023
坂本 佳子, 水谷 哲也, 宮崎 亮, 芳山 三喜雄, 池上 真木彦, 久本 峻平, 鎌倉 昌樹, 中岡 慎治
国内に生息する野生ハナバチ 13 種を対象に DNA・RNA を抽出し、次世代シーケンサーを用いて網羅的解析を実施した。その結果、セイヨウミツバチ、ツツハナバチ、キムネクマバチより未知、あるいは国内未確認のウイルスを検出した。また、すでにミツバチの病原生物として知られる14種について、リアルタイムPCR検出システムを確立し、上記の野生ハナバチ13種における感染・寄生状況を調査した。
農薬が腸内細菌に及ぼす影響を評価するために、まずは、羽化直後のミツバチに均等・均質な腸内細菌叢を与え、14日間安定的に飼育する方法を確立した。当該飼育方法を用いて、ネオニコチノイド、フェニルピラゾール、有機リン、カーバメート、ピレスロイド等の殺虫剤、および殺菌剤、除草剤をそれぞれ2段階で濃度設定で投与し、セイヨウミツバチ3群の腸内細菌叢への影響を解析した。
3種のネオニコチノイド（イミダクロプリド、クロチアニジン、チアメトキサム）をミツバチに投与し、アカリンダニを付着させたところ、ミツバチがダニに気づくまでの時間が短縮し、かつダニを払い落とす行動（グルーミング）の回数が増加した。ネオニコチノイドがミツバチの過敏性を亢進させ、社会性免疫に影響を及ぼす可能性を示唆した。
ミツバチ伝染病の国内分布と近年のトレンドを把握するため、家畜伝染病である腐蛆病、届出伝染病であるバロア症、チョーク病、ノゼマ症、アカリンダニ症の国内発生届出件数データを農林水産省のサイトより入手し、月別・都道府県別で整備した。過去２０年間のトレンドをみたところ、腐蛆病やチョーク病発生は減少傾向にあるが、アカリンダニ症の拡大が見られた。バロア症は一時期減少したが近年増加傾向にあった。
ツツハナバチ属のドラフトゲノムを解析した。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), National Institute for Environmental Studies, 20H00425 - Elucidate latent rules in disruption of biological system
Grants-in-Aid for Scientific Research
19 Jul. 2016 - 31 Mar. 2019
Kawakami Eiryo
We reconstructed human and mouse gene regulatory network based on the enormous public ChIP-seq data. For sporadic and unequal time series data often obtained in medical/biological research, we introduced an algorithm that represent states of data as "landscape" based on multidimensional variables. Utilizing the method, we could stratify patient states and predict state transition of disease progression. We also applied machine learning for the accurate diagnostic and prognostic prediction for epithelial ovarian cancer based on preoperative blood test data. Hereafter, we would like to expand our research aiming at forecasting and preventing disease development by identifying presymptomatic disease state based on health check data and real-world measurement data obtained from various IoT devices.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Institute of Physical and Chemical Research, 16KT0196 - A quantitative model of new strategies for Japan's hyper-aging society
Grants-in-Aid for Scientific Research
01 Apr. 2016 - 31 Mar. 2019
GILMOUR Stuart
This research developed a new model of population dynamics in Japan, and used this model to provide the first comprehensive assessment of major policies to adapt to the rapidly aging society. In this research I assessed two strategies for responding to aging in Japan: a) a strategy based on increasing births in the Japanese population; and b) a strategy based on increased migration. I assessed the impact of both of these strategies by the change in the old age dependency ratio (OADR) up to 50 years in the future. My research showed that neither increasing births nor increasing immigration will have any significant effect on the OADR in future. Even extreme strategies such as increasing the total fertility rate (TFR) to 3 births per woman, or increasing migration to the extent that over 30% of the Japanese population is foreign born, will have minimal effect on the OADR. This research concludes that it is too late for Japan to reverse its hyper-aging.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), 16K04136 - Comprehensive Study of Disease Burden and Its Utilization by Prefecture in Japan
Grants-in-Aid for Scientific Research
01 Apr. 2016 - 31 Mar. 2019
SHIBUYA kenji
This study is the first attempt in Japan to comprehensively analyze the burden of disease not at the national level but also at the prefectures, and apply it to concrete policy analysis. This year we expanded data collection, applied the latest statistical techniques, and improved methodologies. From 1990 to 2017, Japan's overall healthy life expectancy increased from 69.7 to 73.1 years. The top of present main cause of death is cerebrovascular disease and cardiovascular disease nationwide, and main cause of DALYs (Disability-adjusted life years) is back pain. Longevity leads to more disabilities (especially sensory and motor organs). In addition, the burden of degenerative diseases (Alzheimer's disease) is significant nationwide, and urgent measures are required.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), The University of Tokyo, 16H02643 - Theory for effective antiviral strategy based on multiscale mathematical modeling
Grants-in-Aid for Scientific Research
10 Jul. 2015 - 31 Mar. 2019
Iwami Shingo, NAKAOKA SHINJI
In the current era of antiviral drug therapy, combining multiple drugs is a primary approach for improving antiviral effects, reducing the doses of individual drugs, relieving the side effects of strong antiviral drugs, and preventing the emergence of drug-resistant viruses. Mathematical models of viral infection dynamics provide an ideal tool for this purpose. By combining the mathematical modeling of virus dynamics with drug combination theories, we could show the principles by which drug combinations yield a synergistic effect.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Kyushu University, 15KT0107 - mechanism of diversification of shiga toxin-encoding phage, from the ecological aspect
Grants-in-Aid for Scientific Research
01 Apr. 2016 - 31 Mar. 2018
Yoshitoshi Ogura, NAKAOKA shinji, ARIMIZU Yoko
We constructed three Stx2 phage lysogenes of Escherichia coli K-12 and the lysogenes were infected to Dictyosteluim discoideum AX2. But growth of D. discoideum was not affected by the infection of the lysogens at all. Even original O157 strains were not toxic to D. discoideum. Furthermore, inconsistent with several previous studies, we found that infection of O157 strains was not toxic to Acanthamobae castellanii. It is thought that another model protist is required for this analysis. We also showed that the recent and repeated acquisition of the stx2 are occurred in multiple lineages of O26. This suggest the presence of selective pressure to accumulate Stx2 in E. coli O26 in environment. Protist that colonize in bovine intestine is thought to be one of the candidates of the selective pressure.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Kyushu University, 16K15278 - A comprehensive assessment of the burden of disease in Japan
Grants-in-Aid for Scientific Research
01 Apr. 2013 - 31 Mar. 2016
Shibuya Kenji, IKEDA Nayu, GILMOUR Stuart, INOUE Manami, RAHMAN Mizanur, ABE Sarah, NAKAOKA Shinji, SAITO Eiko
This project estimated the national burden of disease; compared the burden of disease by occupational class, which give some information about socioeconomic inequalities in disease burden in Japan; collected data on research funding by major disease cause; and investigated specific burden patterns, such as perinatal mortality, at the Prefectural level. We also generated estimates of risk factors for disease, and their trends over time. Research results were published in major peer-reviewed international journals and also in research presentations at major international conferences. Results were also publicly released through a website, the Meditech Finder.
Using these results, Japanese health policy can be developed based on accurate disease burden information, enabling policy and program decisions to more closely reflect the health needs of the Japanese population now and in the future.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), The University of Tokyo, 25253051 - Multiscale modeling and simulation study for immune inflammatory response at the skin tissue
Grants-in-Aid for Scientific Research
2013 - 2015
Nakaoka Shinji
The purpose of the present research project is to construct multi-scale mathematical models representing disease progression. A particular focus of this study is to describe the progression of atopic dermatitis as a representative skin inflammatory disease. One of mathematical analyses conducted in this research project includes propagation of the inflammatory response at the epidermis tissue. Moreover, interactions amount protease activity and immune response was incorporated to investigate how chronic inflammation is maintained. The later of the project has been in preparation to submit a peer review journal. This work is done by an international collaboration. In addition, study on determining an appropriate numerical computation scheme was examined to develop an efficient and useful computation scheme to implement numerical simulations for multi-scale models. These achievements will be further improved to obtain clear understanding on multi-scale dynamics in disease progression.
Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), 独立行政法人理化学研究所, Principal investigator, Competitive research funding, 25871132 - 細胞レベルの個体群ダイナミクス:微生物生態・免疫系・ガンの数理研究
科学研究費助成事業
2008 - 2010
中岡 慎治
研究内容・意義と重要性
本研究では微生物生態、免疫系、ガンといった環境・医療において重要な生命現象をターゲットにし、これら生命現象に共通する資源競争、個体の成長といった細胞レベルでの基本動作や性質の理解を目指している。本年度は、昨年に引き続いて免疫系の数理研究を中心に研究を進めた。具体的に取り組んだ内容は、次の3つの課題である:(1)造血幹細胞の個体群ダイナミクス研究(2)一細胞計測系に対する数理モデル構築(3)腸内微生物による複雑代謝ネットワークの数理モデル構築。本課題は、定量的測定実験をベースに理論を構築した融合型研究と位置づけられ、異分野融合研究を促進し、生命科学の諸分野にも応用できるような枠組みを作り上げていく第一歩と位置づけられる。この課題に関する研究報告を国内で4回、国内外の国際会議で7回行った。中でも、第3回日中数理生物学コロキウムでは招待講演者として発表した。
研究費使用の主な内訳
情報収集と研究打ち合わせのため、免疫系と数理生物学・システム生物学における国内の関連する学会や研究集会へ参加し、得られた研究成果の発表などを行った。シミュレーション研究を実施するために計算専用コンピューターと研究に必要となる各種書籍を購入した。
日本学術振興会, 特別研究員奨励費, 東京大学, 08J06835
