顔写真

モトイケ イクコ
元池 育子
Ikuko Motoike
所属
東北メディカル・メガバンク機構 ゲノム解析部門
職名
准教授
学位
  • 博士(理学)(京都大学)

  • 修士(学術)(名古屋大学)

所属学協会 2

  • 日本バイオインフォマティクス学会

  • 日本生物物理学会

研究キーワード 5

  • 生命情報システム科学

  • 数理生物物理 非線形科学 反応拡散系

  • Reaction-diffusion computing

  • Nonlinear Science

  • Mathematical Biophysics

研究分野 4

  • ライフサイエンス / 生物物理学 /

  • 自然科学一般 / 生物物理、化学物理、ソフトマターの物理 /

  • 自然科学一般 / 数理物理、物性基礎 /

  • ライフサイエンス / ゲノム生物学 /

論文 74

  1. Dietary habits and plasma lipid concentrations in a general Japanese population. 国際誌

    Mitsuharu Sato, Eiji Hishinuma, Naomi Matsukawa, Yoshiko Shima, Daisuke Saigusa, Ikuko N Motoike, Mana Kogure, Naoki Nakaya, Atsushi Hozawa, Shinichi Kuriyama, Masayuki Yamamoto, Seizo Koshiba, Kengo Kinoshita

    Metabolomics : Official journal of the Metabolomic Society 20 (2) 34-34 2024年3月5日

    DOI: 10.1007/s11306-024-02087-1  

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    INTRODUCTION: Accumulating data on the associations between food consumption and lipid composition in the body is essential for understanding the effects of dietary habits on health. OBJECTIVES: As part of omics research in the Tohoku Medical Megabank Community-Based Cohort Study, this study sought to reveal the dietary impact on plasma lipid concentration in a Japanese population. METHODS: We conducted a correlation analysis of food consumption and plasma lipid concentrations measured using mass spectrometry, for 4032 participants in Miyagi Prefecture, Japan. RESULTS: Our analysis revealed 83 marked correlations between six food categories and the concentrations of plasma lipids in nine subclasses. Previously reported associations, including those between seafood consumption and omega-3 fatty acids, were validated, while those between dairy product consumption and odd-carbon-number fatty acids (odd-FAs) were validated for the first time in an Asian population. Further analysis suggested that dairy product consumption is associated with odd-FAs via sphingomyelin (SM), which suggests that SM is a carrier of odd-FAs. These results are important for understanding odd-FA metabolism with regards to dairy product consumption. CONCLUSION: This study provides insight into the dietary impact on plasma lipid concentration in a Japanese population.

  2. Whole blood transcriptome analysis for age- and gender-specific gene expression profiling in Japanese individuals. 国際誌

    Yu-Ichi Aoki, Keiko Taguchi, Hayato Anzawa, Junko Kawashima, Noriko Ishida, Akihito Otuki, Atsushi Hasegawa, Liam Baird, Takafumi Suzuki, Ikuko N Motoike, Kinuko Ohneda, Kazuki Kumada, Fumiki Katsuoka, Kengo Kinoshita, Masayuki Yamamoto

    Journal of biochemistry 2024年1月24日

    DOI: 10.1093/jb/mvae008  

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    Whole blood transcriptome analysis is a valuable approach in medical research, primarily due to the ease of sample collection and the richness of the information obtained. Since the expression profile of individual genes in the analysis is influenced by medical traits and demographic attributes such as age and gender, there has been a growing demand for a comprehensive database for blood transcriptome analysis. Here, we performed whole blood RNA sequencing (RNA-seq) analysis on 576 participants stratified by age (20-30s and 60-70s) and gender from cohorts of the Tohoku Medical Megabank (TMM). A part of female segment included pregnant women. We did not exclude the globin gene family in our RNA-seq study, which enabled us to identify instances of hereditary persistence of fetal hemoglobin based on the HBG1 and HBG2 expression information. Comparing stratified populations allowed us to identify groups of genes associated with age-related changes and gender differences. We also found that the immune response status, particularly measured by neutrophil-to-lymphocyte ratio (NLR), strongly influences the diversity of individual gene expression profiles in whole blood transcriptome analysis. This stratification has resulted in a dataset that will be highly beneficial for future whole blood transcriptome analysis in the Japanese population.

  3. Identification of predictive biomarkers for endometrial cancer diagnosis and treatment response monitoring using plasma metabolome profiling

    Eiji Hishinuma, Muneaki Shimada, Naomi Matsukawa, Yoshiko Shima, Bin Li, Ikuko N. Motoike, Yusuke Shibuya, Tatsuya Hagihara, Shogo Shigeta, Hideki Tokunaga, Daisuke Saigusa, Kengo Kinoshita, Seizo Koshiba, Nobuo Yaegashi

    Cancer & Metabolism 11 (1) 2023年10月11日

    出版者・発行元:Springer Science and Business Media LLC

    DOI: 10.1186/s40170-023-00317-z  

    eISSN:2049-3002

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    Abstract Background Endometrial cancer (EMC) is the most common female genital tract malignancy with an increasing prevalence in many countries including Japan, a fact that renders early detection and treatment necessary to protect health and fertility. Although early detection and treatment are necessary to further improve the prognosis of women with endometrial cancer, biomarkers that accurately reflect the pathophysiology of EMC patients are still unclear. Therefore, it is clinically critical to identify biomarkers to assess diagnosis and treatment efficacy to facilitate appropriate treatment and development of new therapies for EMC. Methods In this study, wide-targeted plasma metabolome analysis was performed to identify biomarkers for EMC diagnosis and the prediction of treatment responses. The absolute quantification of 628 metabolites in plasma samples from 142 patients with EMC was performed using ultra-high-performance liquid chromatography with tandem mass spectrometry. Results The concentrations of 111 metabolites increased significantly, while the concentrations of 148 metabolites decreased significantly in patients with EMC compared to healthy controls. Specifically, LysoPC and TGs, including unsaturated fatty acids, were reduced in patients with stage IA EMC compared to healthy controls, indicating that these metabolic profiles could be used as early diagnostic markers of EMC. In contrast, blood levels of amino acids such as histidine and tryptophan decreased as the risk of recurrence increased and the stages of EMC advanced. Furthermore, a marked increase in total TG and a decrease in specific TGs and free fatty acids including polyunsaturated fatty acids levels were observed in patients with EMC. These results suggest that the polyunsaturated fatty acids in patients with EMC are crucial for disease progression. Conclusions Our data identified specific metabolite profiles that reflect the pathogenesis of EMC and showed that these metabolites correlate with the risk of recurrence and disease stage. Analysis of changes in plasma metabolite profiles could be applied for the early diagnosis and monitoring of the course of treatment of EMC patients.

  4. Association Between Olfactory Test Data with Multiple Levels of Odor Intensity and Suspected Cognitive Impairment: A Cross-Sectional Study. 国際誌 査読有り

    Shuichi Sato, Takao Imaeda, Shunji Mugikura, Naoko Mori, Masaki Takanashi, Kazumi Hayakawa, Tomo Saito, Makiko Taira, Akira Narita, Mana Kogure, Ippei Chiba, Rieko Hatanaka, Kumi Nakaya, Ikumi Kanno, Ryosuke Ishiwata, Tomohiro Nakamura, Ikuko N Motoike, Naoki Nakaya, Seizo Koshiba, Kengo Kinoshita, Shinichi Kuriyama, Soichi Ogishima, Fuji Nagami, Nobuo Fuse, Atsushi Hozawa

    Journal of Alzheimer's disease : JAD 2023年9月11日

    DOI: 10.3233/JAD-230318  

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    BACKGROUND: Olfactory function decline has recently been reported to be associated with a risk of cognitive impairment. Few population-based studies have included younger adults when examining the association between olfactory test data with multiple odor intensities and suspected cognitive impairment. OBJECTIVE: We investigated the association between high-resolution olfactory test data with fewer odors and suspected cognitive impairments. We also examined the differences between older and younger adults in this association. METHODS: The Japanese version of the Montreal Cognitive Assessment (MoCA-J) was administered to 1,450 participants, with three odor-intensity-level olfactometry using six different odors. Logistic regressions to discriminate suspected cognitive impairment were conducted to examine the association, adjusted for age, sex, education duration, and smoking history. Data were collected from the Program by Tohoku University Tohoku Medical Megabank Organization, with an additional olfactory test conducted between 2019 and 2021. RESULTS: We generally observed that the lower the limit of distinguishable odor intensity was, the higher the MoCA-J score was. The combination of spearmint and stuffy socks contributed most to the distinction between suspected and unsuspected cognitive impairment. Furthermore, the association was significant in women aged 60-74 years (adjusted odds ratio 0.881, 95% confidence interval [0.790, 0.983], p = 0.024). CONCLUSIONS: The results indicate an association between the limit of distinguishable odor intensity and cognitive function. The olfactory test with multiple odor intensity levels using fewer odors may be applicable for the early detection of mild cognitive impairment, especially in older women aged 60-74 years.

  5. Statistical Modeling of Subjective Sleep Quality

    S. Choilek, A. Karashima, I. Motoike, N. Katayama, K. Kinoshita, M. Nakao

    Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference 2023 1-6 2023年7月1日

    DOI: 10.1109/EMBC40787.2023.10340638  

    eISSN:2694-0604

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    Effective maintenance/improvement of sleep quality requires knowledge of how sleep quality is connected to quantitative features of sleep and arbitrarily selected habitual lifestyles, which naturally depend on the demographic characteristics of individuals. To fulfill these needs, a regression model of subjective sleep quality was constructed, whereby one might be able to design a practical strategy for achieving comfortable sleep adapted to individual conditions. Based on data obtained from our previous study, fundamental correlation profiles between day-to-day subjective and quantitative features of sleep were estimated. Obtained correlation profiles involving SRSs, quantitative features of sleep, and sleep habits across a week such as bedtime preference (chronotype), discrepancy between chronotype and social time cue (social jetlag), and habitual sleep-wake pattern (HSWP) were characterized specifically for each self-ratings of sleep quality (SRS) category through backward stepwise Linear Mixed Effect (LME) modeling. The LME model represented SRSs with acceptable accuracy, allowing identification of determinant factors for each category of SRS. The SRS is one possible option to clarify sleep status. In this study, we proposed a possible framework including model-based predictors of SRS in which self-awareness of sleep quality could be improved to facilitate healthy sleep practices.

  6. Tohoku Medical Megabank Brain Magnetic Resonance Imaging Study: Rationale, Design, and Background 査読有り

    JMA Journal 6 (3) 246-264 2023年7月

    出版者・発行元:None

    DOI: 10.31662/jmaj.2022-0220  

    ISSN:2433-328X

    eISSN:2433-3298

  7. Identification of predictive biomarkers for diagnosis and radiation sensitivity of uterine cervical cancer using wide-targeted metabolomics. 国際誌

    Eiji Hishinuma, Muneaki Shimada, Naomi Matsukawa, Bin Li, Ikuko N Motoike, Tatsuya Hagihara, Shogo Shigeta, Hideki Tokunaga, Daisuke Saigusa, Kengo Kinoshita, Seizo Koshiba, Nobuo Yaegashi

    The journal of obstetrics and gynaecology research 49 (8) 2109-2117 2023年6月9日

    DOI: 10.1111/jog.15709  

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    AIM: Uterine cervical cancer (UCC) is the fourth most common cancer in women, responsible for more than 300 000 deaths worldwide. Its early detection, by cervical cytology, and prevention, by vaccinating against human papilloma virus, greatly contribute to reducing cervical cancer mortality in women. However, penetration of the effective prevention of UCC in Japan remains low. Plasma metabolome analysis is widely used for biomarker discovery and the identification of cancer-specific metabolic pathways. Here, we aimed to identify predictive biomarkers for the diagnosis and radiation sensitivity of UCC using wide-targeted plasma metabolomics. METHODS: We analyzed 628 metabolites in plasma samples obtained from 45 patients with UCC using ultra-high-performance liquid chromatography with tandem mass spectrometry. RESULTS: The levels of 47 metabolites were significantly increased and those of 75 metabolites were significantly decreased in patients with UCC relative to healthy controls. Increased levels of arginine and ceramides, and decreased levels of tryptophan, ornithine, glycosylceramides, lysophosphatidylcholine, and phosphatidylcholine were characteristic of patients with UCC. Comparison of metabolite profiles in groups susceptible and non-susceptible to radiation therapy, a treatment for UCC, revealed marked variations in polyunsaturated fatty acid, nucleic acid, and arginine metabolism in the group not susceptible to treatment. CONCLUSIONS: Our findings suggest that the metabolite profile of patients with UCC may be an important indicator for distinguishing these patients from healthy cohorts, and may also be useful for predicting sensitivity to radiotherapy.

  8. Relationship between age-related hearing loss and consumption of coffee and tea.

    Gosuke Watarai, Jun Suzuki, Ikuko N Motoike, Miyuki Sakurai, Ryoukichi Ikeda, Tetsuaki Kawase, Kengo Kinoshita, Atsushi Hozawa, Shinichi Kuriyama, Nobuo Fuse, Masayuki Yamamoto, Yukio Katori

    Geriatrics & gerontology international 2023年5月3日

    DOI: 10.1111/ggi.14589  

  9. Decreased β‐hydroxybutyrate and ketogenic amino acid levels in depressed human adults

    Shiho Sato, Zhiqian Yu, Mai Sakai, Ikuko N. Motoike, Daisuke Saigusa, Ryo Hirayama, Yoshie Kikuchi, Takaaki Abe, Kengo Kinoshita, Seizo Koshiba, Hiroaki Tomita

    European Journal of Neuroscience 2023年2月7日

    出版者・発行元:Wiley

    DOI: 10.1111/ejn.15931  

    ISSN:0953-816X

    eISSN:1460-9568

  10. 血清メタボロームと認知機能変化の関連 NILS-LSAの観察結果から

    寳澤 篤, 大塚 礼, 張 シュ, 菱沼 英史, 元池 育子, 三枝 大輔, 中谷 直樹, 小柴 生造, 荒井 秀典

    Journal of Epidemiology 33 (Suppl.1) 87-87 2023年2月

    出版者・発行元:(一社)日本疫学会

    ISSN:0917-5040

    eISSN:1349-9092

  11. Plasma metabolic disturbances during pregnancy and postpartum in women with depression. 国際誌 査読有り

    Zhiqian Yu, Naomi Matsukawa, Daisuke Saigusa, Ikuko N Motoike, Chiaki Ono, Yasunobu Okamura, Tomomi Onuma, Yuta Takahashi, Mai Sakai, Hisaaki Kudo, Taku Obara, Keiko Murakami, Matusyuki Shirota, Saya Kikuchi, Natsuko Kobayashi, Yoshie Kikuchi, Junichi Sugawara, Naoko Minegishi, Soichi Ogishima, Kengo Kinoshita, Masayuki Yamamoto, Nobuo Yaegashi, Shinichi Kuriyama, Seizo Koshiba, Hiroaki Tomita

    iScience 25 (12) 105666-105666 2022年12月22日

    DOI: 10.1016/j.isci.2022.105666  

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    Examining plasma metabolic profiling during pregnancy and postpartum could help clinicians understand the risk factors for postpartum depression (PPD) development. This analysis targeted paired plasma metabolites in mid-late gestational and 1 month postpartum periods in women with (n = 209) or without (n = 222) PPD. Gas chromatogram-mass spectrometry was used to analyze plasma metabolites at these two time points. Among the 170 objected plasma metabolites, principal component analysis distinguished pregnancy and postpartum metabolites but failed to discriminate women with and without PPD. Compared to women without PPD, those with PPD exhibited 37 metabolites with disparate changes during pregnancy and the 1-month postpartum period and an enriched citrate cycle. Machine learning and multivariate statistical analysis identified two or three compounds that could be potential biomarkers for PPD prediction during pregnancy. Our findings suggest metabolic disturbances in women with depression and may help to elucidate metabolic processes associated with PPD development.

  12. Multiomics and artificial intelligence enabled peripheral blood-based prediction of amnestic mild cognitive impairment

    Yota Tatara, Hiromi Yamazaki, Fumiki Katsuoka, Mitsuru Chiba, Daisuke Saigusa, Shuya Kasai, Tomohiro Nakamura, Jin Inoue, Yuichi Aoki, Miho Shoji, Ikuko Motoike, Yoshinori Tamada, Katsuhito Hashizume, Mikio Shoji, Kengo Kinoshita, Koichi Murashita, Shigeyuki Nakaji, Masayuki Yamamoto, Ken Itoh

    Current Research in Translational Medicine 71 (1) 103367-103367 2022年10月

    出版者・発行元:Elsevier BV

    DOI: 10.1016/j.retram.2022.103367  

    ISSN:2452-3186

  13. Selective Elimination of NRF2-Activated Cells by Competition with Neighboring Cells in the Esophageal Epithelium. 国際誌

    Wataru Hirose, Makoto Horiuchi, Donghan Li, Ikuko N Motoike, Lin Zhang, Hafumi Nishi, Yusuke Taniyama, Takashi Kamei, Mikiko Suzuki, Kengo Kinoshita, Fumiki Katsuoka, Keiko Taguchi, Masayuki Yamamoto

    Cellular and molecular gastroenterology and hepatology 15 (1) 153-178 2022年9月14日

    DOI: 10.1016/j.jcmgh.2022.09.004  

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    BACKGROUND & AIMS: NF-E2-related factor 2 (NRF2) is a transcription factor that regulates cytoprotective gene expression in response to oxidative and electrophilic stresses. NRF2 activity is mainly controlled by Kelch-like ECH-associated protein 1 (KEAP1). Constitutive NRF2 activation by NRF2 mutations or KEAP1 dysfunction results in a poor prognosis for esophageal squamous cell carcinoma (ESCC) through the activation of cytoprotective functions. However, the detailed contributions of NRF2 to ESCC initiation or promotion have not been clarified. Here, we investigated the fate of NRF2-activated cells in the esophageal epithelium. METHODS: We generated tamoxifen-inducible, squamous epithelium-specific Keap1 conditional knockout (Keap1-cKO) mice in which NRF2 was inducibly activated in a subset of cells at the adult stage. Histological, quantitative reverse-transcription polymerase chain reaction (qRT‒PCR), single-cell RNA-sequencing (RNA-seq) and carcinogen experiments were conducted to analyze the Keap1-cKO esophagus. RESULTS: KEAP1-deleted/NRF2-activated cells and cells with normal NRF2 expression (KEAP1-normal cells) coexisted in the Keap1-cKO esophageal epithelium in approximately equal numbers, and NRF2-activated cells formed dysplastic lesions. NRF2-activated cells exhibited weaker attachment to the basement membrane and gradually disappeared from the epithelium. In contrast, neighboring KEAP1-normal cells exhibited accelerated proliferation and started dominating the epithelium but accumulated DNA damage that triggered carcinogenesis upon carcinogen exposure. CONCLUSIONS: Constitutive NRF2 activation promotes the selective elimination of epithelial cells via cell competition, but this competition induces DNA damage in neighboring KEAP1-normal cells, which predisposes them to chemical-induced ESCC.

  14. Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan

    Nobuo Fuse, Miyuki Sakurai, Ikuko N. Motoike, Kaname Kojima, Takako Takai-Igarashi, Naoki Nakaya, Naho Tsuchiya, Tomohiro Nakamura, Mami Ishikuro, Taku Obara, Akiko Miyazawa, Kei Homma, Keisuke Ido, Makiko Taira, Tomoko Kobayashi, Ritsuko Shimizu, Akira Uruno, Eiichi N. Kodama, Kichiya Suzuki, Yohei Hamanaka, Hiroaki Tomita, Junichi Sugawara, Yoichi Suzuki, Fuji Nagami, Soichi Ogishima, Fumiki Katsuoka, Naoko Minegishi, Atsushi Hozawa, Shinichi Kuriyama, Nobuo Yaegashi, Shigeo Kure, Kengo Kinoshita, Masayuki Yamamoto

    Ophthalmology Science 2 (1) 100113-100113 2022年3月

    出版者・発行元:Elsevier BV

    DOI: 10.1016/j.xops.2022.100113  

    ISSN:2666-9145

  15. dbTMM: an integrated database of large-scale cohort, genome and clinical data for the Tohoku Medical Megabank Project

    Soichi Ogishima, Satoshi Nagaie, Satoshi Mizuno, Ryosuke Ishiwata, Keita Iida, Kazuro Shimokawa, Takako Takai-Igarashi, Naoki Nakamura, Sachiko Nagase, Tomohiro Nakamura, Naho Tsuchiya, Naoki Nakaya, Keiko Murakami, Fumihiko Ueno, Tomomi Onuma, Mami Ishikuro, Taku Obara, Shunji Mugikura, Hiroaki Tomita, Akira Uruno, Tomoko Kobayashi, Akito Tsuboi, Shu Tadaka, Fumiki Katsuoka, Akira Narita, Mika Sakurai, Satoshi Makino, Gen Tamiya, Yuichi Aoki, Ritsuko Shimizu, Ikuko N. Motoike, Seizo Koshiba, Naoko Minegishi, Kazuki Kumada, Takahiro Nobukuni, Kichiya Suzuki, Inaho Danjoh, Fuji Nagami, Kozo Tanno, Hideki Ohmomo, Koichi Asahi, Atsushi Shimizu, Atsushi Hozawa, Shinichi Kuriyama, Nobuo Fuse, Teiji Tominaga, Shigeo Kure, Nobuo Yaegashi, Kengo Kinoshita, Makoto Sasaki, Hiroshi Tanaka, Masayuki Yamamoto

    HUMAN GENOME VARIATION 8 (1) 2021年12月

    出版者・発行元:SPRINGERNATURE

    DOI: 10.1038/s41439-021-00175-5  

    eISSN:2054-345X

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    To reveal gene-environment interactions underlying common diseases and estimate the risk for common diseases, the Tohoku Medical Megabank (TMM) project has conducted prospective cohort studies and genomic and multiomics analyses. To establish an integrated biobank, we developed an integrated database called "dbTMM" that incorporates both the individual cohort/clinical data and the genome/multiomics data of 157,191 participants in the Tohoku Medical Megabank project. To our knowledge, dbTMM is the first database to store individual whole-genome data on a variant-by-variant basis as well as cohort/clinical data for over one hundred thousand participants in a prospective cohort study. dbTMM enables us to stratify our cohort by both genome-wide genetic factors and environmental factors, and it provides a research and development platform that enables prospective analysis of large-scale data from genome cohorts.Databases: Integrating megadata for disease research A database integrating 1.3 trillion genome cohort data entries from 157,191 individuals in Japan will facilitate research into the gene-environment interactions underlying common diseases. The Tohoku Medical Megabank integrated database called dbTMM was developed by Soichi Ogishima, Masayuki Yamamoto and colleagues at Tohoku University in Japan. It incorporates the genome, metabolome, proteome, clinical, sociodemographic, lifestyle and environmental data from 84,073 adults, and 73,529 pregnant women and their families, including children. Blood and urine samples were collected from participants and analysed, then obtained genome/multiomics data were stored in dbTMM. Users can stratify the entire population into smaller populations based on multiple data variables, including whole genome variants, to search for statistically significant differences that might warrant further research. The dbTMM is expected to help clarify the genes and gene-environment interactions underlying common diseases and improve disease risk prediction.

  16. Genetic loci for lung function in Japanese adults with adjustment for exhaled nitric oxide levels as airway inflammation indicator

    Mitsuhiro Yamada, Ikuko N. Motoike, Kaname Kojima, Nobuo Fuse, Atsushi Hozawa, Shinichi Kuriyama, Fumiki Katsuoka, Shu Tadaka, Matsuyuki Shirota, Miyuki Sakurai, Tomohiro Nakamura, Yohei Hamanaka, Kichiya Suzuki, Junichi Sugawara, Soichi Ogishima, Akira Uruno, Eiichi N. Kodama, Naoya Fujino, Tadahisa Numakura, Tomohiro Ichikawa, Ayumi Mitsune, Takashi Ohe, Kengo Kinoshita, Masakazu Ichinose, Hisatoshi Sugiura, Masayuki Yamamoto

    COMMUNICATIONS BIOLOGY 4 (1) 2021年11月

    出版者・発行元:NATURE PORTFOLIO

    DOI: 10.1038/s42003-021-02813-8  

    eISSN:2399-3642

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    Lung function reflects the ability of the respiratory system and is utilized for the assessment of respiratory diseases. Because type 2 airway inflammation influences lung function, genome wide association studies (GWAS) for lung function would be improved by adjustment with an indicator of the inflammation. Here, we performed a GWAS for lung function with adjustment for exhaled nitric oxide (FeNO) levels in two independent Japanese populations. Our GWAS with genotype imputations revealed that the RNF5/AGER locus including AGER rs2070600 SNP, which introduces a G82S substitution of AGER, was the most significantly associated with FEV1/FVC. Three other rare missense variants of AGER were further identified. We also found genetic loci with three candidate genes (NOS2, SPSB2 and RIPOR2) associated with FeNO levels. Analyses with the BioBank-Japan GWAS resource revealed genetic links of FeNO and asthma-related traits, and existence of common genetic background for allergic diseases and their biomarkers. Our study identified the genetic locus most strongly associated with airway obstruction in the Japanese population and three genetic loci associated with FeNO, an indicator of type 2 airway inflammation in adults.Yamada, Motoike, Kojima et al. undertake a GWAS study on 19,722 participants from two Japanese populations for lung function with adjustment for fractional exhaled nitric oxide levels to account for airway inflammation. The authors identify variants of the RNF5/AGER locus and explore their three-dimensional protein interactions to better investigate the association between these variants and lung function.

  17. 多層オミックスと機械学習による軽度認知障害の予測モデルの構築

    多田羅 洋太, 中村 智洋, 千葉 満, 三枝 大輔, 山嵜 博未, 勝岡 史城, 葛西 秋宅, 川瀬 倫子, 本間 リナ, 松田 りら, 藤本 哲太, 荘司 美穂, 元池 育子, 玉田 嘉紀, 橋爪 克仁, 東海林 幹夫, 木下 賢吾, 伊東 健

    Dementia Japan 35 (4) 660-660 2021年10月

    出版者・発行元:(一社)日本認知症学会

    ISSN:1342-646X

  18. Subjective sleep quality, quantitative sleep features, and their associations dependent on demographic characteristics, habitual sleep–wake patterns, and distinction of weekdays/weekends

    Siwalee Choilek, Akihiro Karashima, Ikuko Motoike, Norihiro Katayama, Kengo Kinoshita, Mitsuyuki Nakao

    Sleep and Biological Rhythms 19 (4) 369-381 2021年10月

    DOI: 10.1007/s41105-021-00326-9  

    ISSN:1446-9235

    eISSN:1479-8425

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    Generally applicable qualifications of sleep and principles for achieving better sleep are difficult to design, because sleep quality can depend on individual demographic characteristics and lifestyles. In this study, the static and dynamic features of sleep–wake patterns were analyzed in association with quantitative sleep-related parameters and self-rated sleep quality to serve as a practical selection of sleep–wake patterns fitted to individual conditions. Data obtained over a 2-week period by actigraphy from university students and information technology workers were measured to obtain a daily subjective rating of sleep quality using the Oguri–Shirakawa–Azumi (OSA) sleep inventory. Qualitative sleep quality in terms of OSA score and quantitative sleep-related and chronobiological features were analyzed with regard to their dependency on the demographic characteristics, habitual sleep–wake patterns (HSWP), and distinction of weekdays/weekends. Multi-factor ANOVA was used to further investigate their dependencies regarding multiple ways of interactions between the demographic characteristics, HSWP, and distinction of weekdays/weekends. Subjective sleep quality and quantitative sleep-related parameters depended on the demographic characteristics, and so did their associations. The classification of day-to-day variations in HSWP showed four clusters that were effective factors for understanding their dependencies. Multi-factor analysis revealed demographic characteristics, HSWP, distinction of weekdays/weekends, and their multi-way interactions up to 3rd order as significant effectors of qualitative and quantitative quality of sleep. This study clarified how quantitative sleep-related parameters, subjective sleep quality, and their associations depended on demographic characteristics. Furthermore, their dependency was understood as a combination of multi-way interactions between the demographic characteristics, HSWP, and the distinction of weekdays/weekends. Our findings could provide a basis for the design of individually matched sleep–wake patterns.

  19. Comparison of Kit-Based Metabolomics with Other Methodologies in a Large Cohort, towards Establishing Reference Values

    Daisuke Saigusa, Eiji Hishinuma, Naomi Matsukawa, Masatomo Takahashi, Jin Inoue, Shu Tadaka, Ikuko N. Motoike, Atsushi Hozawa, Yoshihiro Izumi, Takeshi Bamba, Kengo Kinoshita, Kim Ekroos, Seizo Koshiba, Masayuki Yamamoto

    Metabolites 11 (10) 652-652 2021年9月24日

    出版者・発行元:MDPI AG

    DOI: 10.3390/metabo11100652  

    eISSN:2218-1989

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    Metabolic profiling is an omics approach that can be used to observe phenotypic changes, making it particularly attractive for biomarker discovery. Although several candidate metabolites biomarkers for disease expression have been identified in recent clinical studies, the reference values of healthy subjects have not been established. In particular, the accuracy of concentrations measured by mass spectrometry (MS) is unclear. Therefore, comprehensive metabolic profiling in large-scale cohorts by MS to create a database with reference ranges is essential for evaluating the quality of the discovered biomarkers. In this study, we tested 8700 plasma samples by commercial kit-based metabolomics and separated them into two groups of 6159 and 2541 analyses based on the different ultra-high-performance tandem mass spectrometry (UHPLC-MS/MS) systems. We evaluated the quality of the quantified values of the detected metabolites from the reference materials in the group of 2541 compared with the quantified values from other platforms, such as nuclear magnetic resonance (NMR), supercritical fluid chromatography tandem mass spectrometry (SFC-MS/MS) and UHPLC-Fourier transform mass spectrometry (FTMS). The values of the amino acids were highly correlated with the NMR results, and lipid species such as phosphatidylcholines and ceramides showed good correlation, while the values of triglycerides and cholesterol esters correlated less to the lipidomics analyses performed using SFC-MS/MS and UHPLC-FTMS. The evaluation of the quantified values by MS-based techniques is essential for metabolic profiling in a large-scale cohort.

  20. Wide-Targeted Metabolome Analysis Identifies Potential Biomarkers for Prognosis Prediction of Epithelial Ovarian Cancer. 国際誌

    Eiji Hishinuma, Muneaki Shimada, Naomi Matsukawa, Daisuke Saigusa, Bin Li, Kei Kudo, Keita Tsuji, Shogo Shigeta, Hideki Tokunaga, Kazuki Kumada, Keigo Komine, Hidekazu Shirota, Yuichi Aoki, Ikuko N Motoike, Jun Yasuda, Kengo Kinoshita, Masayuki Yamamoto, Seizo Koshiba, Nobuo Yaegashi

    Toxins 13 (7) 2021年6月30日

    DOI: 10.3390/toxins13070461  

    eISSN:2072-6651

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    Epithelial ovarian cancer (EOC) is a fatal gynecologic cancer, and its poor prognosis is mainly due to delayed diagnosis. Therefore, biomarker identification and prognosis prediction are crucial in EOC. Altered cell metabolism is a characteristic feature of cancers, and metabolomics reflects an individual's current phenotype. In particular, plasma metabolome analyses can be useful for biomarker identification. In this study, we analyzed 624 metabolites, including uremic toxins (UTx) in plasma derived from 80 patients with EOC using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Compared with the healthy control, we detected 77 significantly increased metabolites and 114 significantly decreased metabolites in EOC patients. Especially, decreased concentrations of lysophosphatidylcholines and phosphatidylcholines and increased concentrations of triglycerides were observed, indicating a metabolic profile characteristic of EOC patients. After calculating the parameters of each metabolic index, we found that higher ratios of kynurenine to tryptophan correlates with worse prognosis in EOC patients. Kynurenine, one of the UTx, can affect the prognosis of EOC. Our results demonstrated that plasma metabolome analysis is useful not only for the diagnosis of EOC, but also for predicting prognosis with the variation of UTx and evaluating response to chemotherapy.

  21. Chronic Hypercapnic Respiratory Failure in an Adult Patient with Silver-Russell Syndrome.

    Mariko Hakamata, Satoshi Hokari, Yasuyoshi Ohshima, Masayo Kagami, Sakae Saito, Ikuko N Motoike, Taiki Abe, Nobumasa Aoki, Masachika Hayashi, Satoshi Watanabe, Toshiyuki Koya, Toshiaki Kikuchi

    Internal medicine (Tokyo, Japan) 60 (12) 1921-1926 2021年6月15日

    DOI: 10.2169/internalmedicine.5479-20  

    ISSN:0918-2918

    eISSN:1349-7235

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    A 31-year-old woman who was clinically diagnosed with Silver-Russell syndrome (SRS) in childhood was admitted with complaints of dyspnea. She had hypercapnic respiratory failure accompanied by nocturnal hypoventilation. Computed tomography revealed systemic muscle atrophy and superior mesenteric artery syndrome; however, the bilateral lung fields were normal. She was treated with nocturnal noninvasive positive pressure ventilation and showed improvement of respiratory failure. In this case, loss of methylation on chromosome 11p15 and maternal uniparental disomy of chromosome 7, which are the common causes of SRS, were not detected. This is a rare case of adult SRS manifesting as chronic hypercapnic respiratory failure.

  22. Japonica Array NEO with increased genome-wide coverage and abundant disease risk SNPs. 国際誌

    Mika Sakurai-Yageta, Kazuki Kumada, Chinatsu Gocho, Satoshi Makino, Akira Uruno, Shu Tadaka, Ikuko N Motoike, Masae Kimura, Shin Ito, Akihito Otsuki, Akira Narita, Hisaaki Kudo, Yuichi Aoki, Inaho Danjoh, Jun Yasuda, Hiroshi Kawame, Naoko Minegishi, Seizo Koshiba, Nobuo Fuse, Gen Tamiya, Masayuki Yamamoto, Kengo Kinoshita

    Journal of biochemistry 170 (3) 399-410 2021年5月13日

    DOI: 10.1093/jb/mvab060  

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    Ethnic-specific SNP arrays are becoming more important to increase the power of genome-wide association studies in diverse population. In the Tohoku Medical Megabank Project, we have been developing a series of Japonica Arrays (JPA) for genotyping participants based on reference panels constructed from whole-genome sequence data of the Japanese population. Here, we designed a novel version of the SNP array for the Japanese population, called Japonica Array NEO (JPA NEO), comprising a total of 666,883 markers. Among them, 654,246 tag SNPs of autosomes and X chromosome were selected from an expanded reference panel of 3,552 Japanese, 3.5KJPNv2, using pairwise r2 of linkage disequilibrium measures. Additionally, 28,298 markers were included for the evaluation of previously identified disease risk markers from the literature and databases, and those present in the Japanese population were extracted using the reference panel. Through genotyping 286 Japanese samples, we found that the imputation quality r2 and INFO score in the minor allele frequency bin >2.5-5% were >0.9 and >0.8, respectively, and >12 million markers were imputed with an INFO score >0.8. From these results, JPA NEO is a promising tool for genotyping the Japanese population with genome-wide coverage, contributing to the development of genetic risk scores.

  23. GWAS Identified IL4R and the Major Histocompatibility Complex Region as the Associated Loci of Total Serum IgE Levels in 9,260 Japanese Individuals. 国際誌

    Kosuke Shido, Kaname Kojima, Matsuyuki Shirota, Kenshi Yamasaki, Ikuko N Motoike, Atsushi Hozawa, Soichi Ogishima, Naoko Minegishi, Kozo Tanno, Fumiki Katsuoka, Gen Tamiya, Setsuya Aiba, Masayuki Yamamoto, Kengo Kinoshita

    The Journal of investigative dermatology 141 (11) 2749-2752 2021年4月14日

    DOI: 10.1016/j.jid.2021.02.762  

    ISSN:0022-202X

    eISSN:1523-1747

  24. Possible Somatic Mosaicism of Novel FUS Variant in Familial Amyotrophic Lateral Sclerosis. 国際誌

    Shin Hisahara, Ayumi Nishiyama, Emiko Tsuda, Syuuichirou Suzuki, Akihiro Matsumura, Aki Ishikawa, Akihiro Sakurai, Ikuko N Motoike, Masashi Aoki, Yoko Aoki, Shun Shimohama

    Neurology. Genetics 7 (1) e552 2021年2月

    DOI: 10.1212/NXG.0000000000000552  

  25. jMorp updates in 2020: large enhancement of multi-omics data resources on the general Japanese population. 国際誌

    Shu Tadaka, Eiji Hishinuma, Shohei Komaki, Ikuko N Motoike, Junko Kawashima, Daisuke Saigusa, Jin Inoue, Jun Takayama, Yasunobu Okamura, Yuichi Aoki, Matsuyuki Shirota, Akihito Otsuki, Fumiki Katsuoka, Atsushi Shimizu, Gen Tamiya, Seizo Koshiba, Makoto Sasaki, Masayuki Yamamoto, Kengo Kinoshita

    Nucleic acids research 49 (D1) D536-D544 2021年1月8日

    DOI: 10.1093/nar/gkaa1034  

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    In the Tohoku Medical Megabank project, genome and omics analyses of participants in two cohort studies were performed. A part of the data is available at the Japanese Multi Omics Reference Panel (jMorp; https://jmorp.megabank.tohoku.ac.jp) as a web-based database, as reported in our previous manuscript published in Nucleic Acid Research in 2018. At that time, jMorp mainly consisted of metabolome data; however, now genome, methylome, and transcriptome data have been integrated in addition to the enhancement of the number of samples for the metabolome data. For genomic data, jMorp provides a Japanese reference sequence obtained using de novo assembly of sequences from three Japanese individuals and allele frequencies obtained using whole-genome sequencing of 8,380 Japanese individuals. In addition, the omics data include methylome and transcriptome data from ∼300 samples and distribution of concentrations of more than 755 metabolites obtained using high-throughput nuclear magnetic resonance and high-sensitivity mass spectrometry. In summary, jMorp now provides four different kinds of omics data (genome, methylome, transcriptome, and metabolome), with a user-friendly web interface. This will be a useful scientific data resource on the general population for the discovery of disease biomarkers and personalized disease prevention and early diagnosis.

  26. Enhancer remodeling promotes tumor-initiating activity in NRF2-activated non-small cell lung cancers

    Keito Okazaki, Hayato Anzawa, Zun Liu, Nao Ota, Hiroshi Kitamura, Yoshiaki Onodera, Md Morshedul Alam, Daisuke Matsumaru, Takuma Suzuki, Fumiki Katsuoka, Shu Tadaka, Ikuko Motoike, Mika Watanabe, Kazuki Hayasaka, Akira Sakurada, Yoshinori Okada, Masayuki Yamamoto, Takashi Suzuki, Kengo Kinoshita, Hiroki Sekine, Hozumi Motohashi

    Nature Communications 11 (1) 2020年12月

    DOI: 10.1038/s41467-020-19593-0  

    eISSN:2041-1723

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    Transcriptional dysregulation, which can be caused by genetic and epigenetic alterations, is a fundamental feature of many cancers. A key cytoprotective transcriptional activator, NRF2, is often aberrantly activated in non-small cell lung cancers (NSCLCs) and supports both aggressive tumorigenesis and therapeutic resistance. Herein, we find that persistently activated NRF2 in NSCLCs generates enhancers at gene loci that are not normally regulated by transiently activated NRF2 under physiological conditions. Elevated accumulation of CEBPB in NRF2-activated NSCLCs is found to be one of the prerequisites for establishment of the unique NRF2-dependent enhancers, among which the NOTCH3 enhancer is shown to be critical for promotion of tumor-initiating activity. Enhancer remodeling mediated by NRF2-CEBPB cooperativity promotes tumor-initiating activity and drives malignancy of NRF2-activated NSCLCs via establishment of the NRF2-NOTCH3 regulatory axis.

  27. Improved metabolomic data-based prediction of depressive symptoms using nonlinear machine learning with feature selection 国際誌 査読有り

    Yuta Takahashi, Masao Ueki, Makoto Yamada, Gen Tamiya, Ikuko N. Motoike, Daisuke Saigusa, Miyuki Sakurai, Fuji Nagami, Soichi Ogishima, Seizo Koshiba, Kengo Kinoshita, Masayuki Yamamoto, Hiroaki Tomita

    Translational Psychiatry 10 (1) 157-157 2020年12月1日

    DOI: 10.1038/s41398-020-0831-9  

    eISSN:2158-3188

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    © 2020, The Author(s). To solve major limitations in algorithms for the metabolite-based prediction of psychiatric phenotypes, a novel prediction model for depressive symptoms based on nonlinear feature selection machine learning, the Hilbert–Schmidt independence criterion least absolute shrinkage and selection operator (HSIC Lasso) algorithm, was developed and applied to a metabolomic dataset with the largest sample size to date. In total, 897 population-based subjects were recruited from the communities affected by the Great East Japan Earthquake; 306 metabolite features (37 metabolites identified by nuclear magnetic resonance measurements and 269 characterized metabolites based on the intensities from mass spectrometry) were utilized to build prediction models for depressive symptoms as evaluated by the Center for Epidemiologic Studies-Depression Scale (CES-D). The nested fivefold cross-validation was used for developing and evaluating the prediction models. The HSIC Lasso-based prediction model showed better predictive power than the other prediction models, including Lasso, support vector machine, partial least squares, random forest, and neural network. l-leucine, 3-hydroxyisobutyrate, and gamma-linolenyl carnitine frequently contributed to the prediction. We have demonstrated that the HSIC Lasso-based prediction model integrating nonlinear feature selection showed improved predictive power for depressive symptoms based on metabolome data as well as on risk metabolites based on nonlinear statistics in the Japanese population. Further studies should use HSIC Lasso-based prediction models with different ethnicities to investigate the generality of each risk metabolite for predicting depressive symptoms.

  28. Identification of critical genetic variants associated with metabolic phenotypes of the Japanese population. 国際誌

    Seizo Koshiba, Ikuko N Motoike, Daisuke Saigusa, Jin Inoue, Yuichi Aoki, Shu Tadaka, Matsuyuki Shirota, Fumiki Katsuoka, Gen Tamiya, Naoko Minegishi, Nobuo Fuse, Kengo Kinoshita, Masayuki Yamamoto

    Communications biology 3 (1) 662-662 2020年11月11日

    DOI: 10.1038/s42003-020-01383-5  

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    We performed a metabolome genome-wide association study for the Japanese population in the prospective cohort study of Tohoku Medical Megabank. By combining whole-genome sequencing and nontarget metabolome analyses, we identified a large number of novel associations between genetic variants and plasma metabolites. Of the identified metabolite-associated genes, approximately half have already been shown to be involved in various diseases. We identified metabolite-associated genes involved in the metabolism of xenobiotics, some of which are from intestinal microorganisms, indicating that the identified genetic variants also markedly influence the interaction between the host and symbiotic bacteria. We also identified five associations that appeared to be female-specific. A number of rare variants that influence metabolite levels were also found, and combinations of common and rare variants influenced the metabolite levels more profoundly. These results support our contention that metabolic phenotyping provides important insights into how genetic and environmental factors provoke human diseases.

  29. Longitudinal plasma amino acid profiling with maternal genomic background throughout human pregnancy 国際誌 査読有り

    Matsuyuki Shirota, Daisuke Saigusa, Riu Yamashita, Yasutake Kato, Mitsuyo Matsumoto, Junya Yamagishi, Noriko Ishida, Kazuki Kumada, Yuji Oe, Hisaaki Kudo, Junji Yokozawa, Yoko Kuroki, Ikuko Motoike, Fumiki Katsuoka, Masao Nagasaki, Seizo Koshiba, Keiko Nakayama, Osamu Tanabe, Jun Yasuda, Shigeo Kure, Kengo Kinoshita, Hirohito Metoki, Shinichi Kuriyama, Nobuo Yaegashi, Masayuki Yamamoto, Junichi Sugawara

    Medical Mass Spectrometry 4 (1) 36-49 2020年4月16日

    DOI: 10.24508/mms.2020.06.001  

  30. Impacts of NRF2 activation in non–small-cell lung cancer cell lines on extracellular metabolites 国際誌 査読有り

    Daisuke Saigusa, Ikuko N. Motoike, Sakae Saito, Michael Zorzi, Yuichi Aoki, Hiroshi Kitamura, Mikiko Suzuki, Fumiki Katsuoka, Hirofumi Ishii, Kengo Kinoshita, Hozumi Motohashi, Masayuki Yamamoto

    Cancer Science 111 (2) 667-678 2020年2月1日

    DOI: 10.1111/cas.14278  

    ISSN:1347-9032

    eISSN:1349-7006

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    © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. Aberrant activation of NRF2 is as a critical prognostic factor that drives the malignant progression of various cancers. Cancer cells with persistent NRF2 activation heavily rely on NRF2 activity for therapeutic resistance and aggressive tumorigenic capacity. To clarify the metabolic features of NRF2-activated lung cancers, we conducted targeted metabolomic (T-Met) and global metabolomic (G-Met) analyses of non–small-cell lung cancer (NSCLC) cell lines in combination with exome and transcriptome analyses. Exome analysis of 88 cell lines (49 adenocarcinoma, 14 large cell carcinoma, 15 squamous cell carcinoma and 10 others) identified non–synonymous mutations in the KEAP1, NRF2 and CUL3 genes. Judging from the elevated expression of NRF2 target genes, these mutations are expected to result in the constitutive stabilization of NRF2. Out of the 88 cell lines, 52 NSCLC cell lines (29 adenocarcinoma, 10 large cell carcinoma, 9 squamous cell carcinoma and 4 others) were subjected to T-Met analysis. Classification of the 52 cell lines into three groups according to the NRF2 target gene expression enabled us to draw typical metabolomic signatures induced by NRF2 activation. From the 52 cell lines, 18 NSCLC cell lines (14 adenocarcinoma, 2 large cell carcinoma, 1 squamous cell carcinoma and 1 others) were further chosen for G-Met and detailed transcriptome analyses. G-Met analysis of their culture supernatants revealed novel metabolites associated with NRF2 activity, which may be potential diagnostic biomarkers of NRF2 activation. This study also provides useful information for the exploration of new metabolic nodes for selective toxicity towards NRF2-activated NSCLC.

  31. Consistency index of daily activity pattern and its correlations with subjective ratings of QOL 査読有り

    Ryota Amano, Akihiro Karashima, Ikuko Motoike, Norihiro Katayama, Kengo Kinoshita, Mitsuyuki Nakao

    Sleep and Biological Rhythms 18 (4) 297-304 2020年

    DOI: 10.1007/s41105-020-00271-z  

    ISSN:1446-9235

    eISSN:1479-8425

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    © 2020, Japanese Society of Sleep Research. Since sleep is under circadian and homeostatic regulation, the status of regulatory mechanisms can be known from daily activity patterns, including both sleep and wake states. Therefore, the relationship between their quantitative characterization and associated subjective QOL can be expected to provide practical knowledge for maintaining/improving QOL. An index quantifying the consistency of daily activity patterns over days, the activity consistency index (ACI), was developed, and its correlations with subjective QOL ratings based on the Pittsburgh sleep quality index (PSQI) and the Kessler Psychological Distress Scale (K6) were analyzed using actigraphy data obtained from university students and IT workers. The consistency of the parametrically transformed actigraphy data was quantified using a parameter set tuned to optimize an ensemble correlation between the consistency measure and QOL. Comparisons of ACI with a previously proposed index (SRI: sleep regularity index) were made according to their correlations with the participants’ subjective ratings of QOL. The comparison of ACI and SRI with respect to the various quantitative features of daily activity revealed that ACI tuned to PSQI was correlated only with mean sleep-onset time and mean sleep duration, while SRI was correlated with most of the quantitative features of sleep. In addition, the correlation profile showed gender dependency. For male and female subjects in their 20 s, the analysis indicated a significant correlation between PSQI and ACI, but not between PSQI and SRI. ACI was shown to work well as an index of daily activity patterns relevant to subjective sleep quality. This ability suggests that ACI could be a basis for predicting subjective sleep quality. Through evaluating daily activity patterns using ACI, an individual may be able to select an appropriate lifestyle for maintaining/improving QOL.

  32. Relationship between Dynamics of Physiological Signals and Subjective Quality of Life and Its Lifestyle Dependency 査読有り

    R. Amano, A. Karashima, I. Motoike, N. Katayama, K. Kinoshita, M. Nakao

    Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS 546-549 2019年7月

    DOI: 10.1109/EMBC.2019.8857083  

    ISSN:1557-170X

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    © 2019 IEEE. In terms of preventive healthcare, how adopted lifestyle maintains healthy states or leads to pathological states is an essential issue. In this study, for the healthy subjects, their daily patterns of heart rate variability (HRV) and behavioral activity dynamics were analyzed in association with subjective quality of life (QOL), and how the relationship between the physiological signal dynamics and QOL is differentiated by the chronotype (sleep-wake pattern) was investigated. As a result, the morning type subjects were found to show higher sequential variation in R-R interval (rMSSD) and behavioral activity, and to have higher sleep quality and non-depressive tendency. Even the evening type subjects could have higher sleep quality under the condition that rMSSD shows a dip around early afternoon and keep a higher level of activity during the daytime, which may be due to realization of steady entrainment to the circadian time cues. Through this study, fundamental knowledge for preventive healthcare was obtained for us to help people's choice of an appropriate lifestyle for their health.

  33. メタボロームデータを用いた非線形変数選択機械学習によるうつ状態の予測

    高橋 雄太, 植木 優夫, 山田 誠, 田宮 元, 元池 育子, 三枝 大輔, 櫻井 美由紀, 長神 風二, 小柴 生造, 木下 賢吾, 山本 雅之, 富田 博秋

    精神神経学雑誌 (2019特別号) S609-S609 2019年6月

    出版者・発行元:(公社)日本精神神経学会

    ISSN:0033-2658

  34. Identification of genetic alterations in extramammary Paget disease using whole exome analysis 国際誌 査読有り

    Yukiko Kiniwa, Jun Yasuda, Sakae Saito, Rumiko Saito, Ikuko N. Motoike, Inaho Danjoh, Kengo Kinoshita, Nobuo Fuse, Masayuki Yamamoto, Ryuhei Okuyama

    Journal of Dermatological Science 94 (1) 229-235 2019年4月

    DOI: 10.1016/j.jdermsci.2019.03.006  

    ISSN:0923-1811

    eISSN:1873-569X

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    © 2019 The Author(s) Background: Extramammary Paget disease (EMPD)is a rare cutaneous malignant neoplasm, and the genomic alterations underlying its pathogenesis are unknown. Objective: To identify tumor-specific genomic alterations in EMPD. Methods: Exome analysis was performed in specimens from three EMPD patients, and target amplicon sequencing was done for genes frequently mutated in other adenocarcinomas. Results: Exome analysis revealed recurrent somatic mutations in several genes, includingTP53, PIK3CA, and ERBB2. We identified additional candidate exons by searching the COSMIC database for exons that are frequently mutated in other adenocarcinomas. We obtained 19 exons in 12 genes as candidate exons, and performed target amplicon sequencing in samples obtained from EMPD patients. New somatic mutations in the TP53 gene were identified in six EMPD patients. Single nucleotide polymorphism analysis revealed multiple chromosomal alterations in three EMPD specimens, and two specimens exhibited amplification of chromosome 12p13 and losses of 3p21–24, 7q22 and 13q12–21. Conclusion: Our comprehensive genetic analysis identified novel genomic alterations, and will inform treatment options for EMPD.

  35. Genome analyses for the Tohoku Medical Megabank Project towards establishment of personalized healthcare 国際誌 査読有り

    Jun Yasuda, Kengo Kinoshita, Fumiki Katsuoka, Inaho Danjoh, Mika Sakurai-Yageta, Ikuko N. Motoike, Yoko Kuroki, Sakae Saito, Kaname Kojima, Matsuyuki Shirota, Daisuke Saigusa, Akihito Otsuki, Junko Kawashima, Yumi Yamaguchi-Kabata, Shu Tadaka, Yuichi Aoki, Takahiro Mimori, Kazuki Kumada, Jin Inoue, Satoshi Makino, Miho Kuriki, Nobuo Fuse, Seizo Koshiba, Osamu Tanabe, Masao Nagasaki, Gen Tamiya, Ritsuko Shimizu, Takako Takai-Igarashi, Soichi Ogishima, Atsushi Hozawa, Shinichi Kuriyama, Junichi Sugawara, Akito Tsuboi, Hideyasu Kiyomoto, Tadashi Ishii, Hiroaki Tomita, Naoko Minegishi, Yoichi Suzuki, Kichiya Suzuki, Hiroshi Kawame, Hiroshi Tanaka, Yasuyuki Taki, Nobuo Yaegashi, Shigeo Kure, Fuji Nagami, Kenjiro Kosaki, Yoichi Sutoh, Tsuyoshi Hachiya, Atsushi Shimizu, Makoto Sasaki, Masayuki Yamamoto

    Journal of Biochemistry 165 (2) 139-158 2019年2月1日

    出版者・発行元:Journal of Biochemistry

    DOI: 10.1093/jb/mvy096  

    ISSN:0021-924X

    eISSN:1756-2651

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    © The Author(s) 2018. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved. Personalized healthcare (PHC) based on an individual's genetic make-up is one of the most advanced, yet feasible, forms of medical care. The Tohoku Medical Megabank (TMM) Project aims to combine population genomics, medical genetics and prospective cohort studies to develop a critical infrastructure for the establishment of PHC. To date, a TMM CommCohort (adult general population) and a TMM BirThree Cohort (birth+three-generation families) have conducted recruitments and baseline surveys. Genome analyses as part of the TMM Project will aid in the development of a high-fidelity whole-genome Japanese reference panel, in designing custom single-nucleotide polymorphism (SNP) arrays specific to Japanese, and in estimation of the biological significance of genetic variations through linked investigations of the cohorts. Whole-genome sequencing from >3,500 unrelated Japanese and establishment of a Japanese reference genome sequence from long-read data have been done. We next aim to obtain genotype data for all TMM cohort participants (>150,000) using our custom SNP arrays. These data will help identify disease-associated genomic signatures in the Japanese population, while genomic data from TMM BirThree Cohort participants will be used to improve the reference genome panel. Follow-up of the cohort participants will allow us to test the genetic markers and, consequently, contribute to the realization of PHC.

  36. Genome-wide analysis of glucocorticoid-responsive transcripts in the hypothalamic paraventricular region of male rats 国際誌 査読有り

    Keiichi Itoi, Ikuko Motoike, Ying Liu, Sam Clokie, Yasumasa Iwasaki, Katsuya Uchida, Tatsuya Sato, Greti Aguilera

    Endocrinology (United States) 160 (1) 38-54 2019年1月1日

    DOI: 10.1210/en.2018-00535  

    ISSN:0013-7227

    eISSN:1945-7170

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    © 2019 Endocrine Society. Glucocorticoids (GCs) are essential for stress adaptation, acting centrally and in the periphery. Corticotropin-releasing factor (CRF), a major regulator of adrenal GC synthesis, is produced in the paraventricular nucleus of the hypothalamus (PVH), which contains multiple neuroendocrine and preautonomic neurons. GCs may be involved in diverse regulatory mechanisms in the PVH, but the target genes of GCs are largely unexplored except for the CRF gene (Crh), a well-known target for GC negative feedback. Using a genome-wide RNA-sequencing analysis, we identified transcripts that changed in response to either high-dose corticosterone (Cort) exposure for 12 days (12-day high Cort), corticoid deprivation for 7 days (7-day ADX), or acute Cort administration. Among others, canonical GC target genes were upregulated prominently by 12-day high Cort. Crh was upregulated or downregulated most prominently by either 7-day ADX or 12-day high Cort, emphasizing the recognized feedback effects of GC on the hypothalamic-pituitary-adrenal (HPA) axis. Concomitant changes in vasopressin and apelin receptor gene expression are likely to contribute to HPA repression. In keeping with the pleotropic cellular actions of GCs, 7-day ADX downregulated numerous genes of a broad functional spectrum. The transcriptome response signature differed markedly between acute Cort injection and 12-day high Cort. Remarkably, six immediate early genes were upregulated 1 hour after Cort injection, which was confirmed by quantitative reverse transcription PCR and semiquantitative in situ hybridization. This study may provide a useful database for studying the regulatory mechanisms of GC-dependent gene expression and repression in the PVH.

  37. 3.5KJPNv2: an allele frequency panel of 3552 Japanese individuals including the X chromosome. 国際誌 査読有り

    Shu Tadaka, Fumiki Katsuoka, Masao Ueki, Kaname Kojima, Satoshi Makino, Sakae Saito, Akihito Otsuki, Chinatsu Gocho, Mika Sakurai-Yageta, Inaho Danjoh, Ikuko N Motoike, Yumi Yamaguchi-Kabata, Matsuyuki Shirota, Seizo Koshiba, Masao Nagasaki, Naoko Minegishi, Atsushi Hozawa, Shinichi Kuriyama, Atsushi Shimizu, Jun Yasuda, Nobuo Fuse, Gen Tamiya, Masayuki Yamamoto, Kengo Kinoshita

    Human genome variation 6 28-28 2019年

    出版者・発行元:Cold Spring Harbor Laboratory

    DOI: 10.1038/s41439-019-0059-5  

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    The first step towards realizing personalized healthcare is to catalog the genetic variations in a population. Since the dissemination of individual-level genomic information is strictly controlled, it will be useful to construct population-level allele frequency panels with easy-to-use interfaces. In the Tohoku Medical Megabank Project, we sequenced nearly 4000 individuals from a Japanese population and constructed an allele frequency panel of 3552 individuals after removing related samples. The panel is called the 3.5KJPNv2. It was constructed by using a standard pipeline including the 1KGP and gnomAD algorithms to reduce technical biases and to allow comparisons to other populations. Our database is the first large-scale panel providing the frequencies of variants present on the X chromosome and on the mitochondria in the Japanese population. All the data are available on our original database at https://jmorp.megabank.tohoku.ac.jp.

  38. Metabolomic changes in the mouse retina after optic nerve injury 国際誌 査読有り

    Kota Sato, Daisuke Saigusa, Ritsumi Saito, Amane Fujioka, Yurika Nakagawa, Koji M. Nishiguchi, Taiki Kokubun, Ikuko N. Motoike, Kazuichi Maruyama, Kazuko Omodaka, Yukihiro Shiga, Akira Uruno, Seizo Koshiba, Masayuki Yamamoto, Toru Nakazawa

    Scientific Reports 8 (1) 11930-11930 2018年12月1日

    DOI: 10.1038/s41598-018-30464-z  

    eISSN:2045-2322

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    © 2018, The Author(s). In glaucoma, although axonal injury drives retinal ganglion cell (RGC) death, little is known about the underlying pathomechanisms. To provide new mechanistic insights and identify new biomarkers, we combined latest non-targeting metabolomics analyses to profile altered metabolites in the mouse whole retina 2, 4, and 7 days after optic nerve crush (NC). Ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry and liquid chromatography Fourier transform mass spectrometry covering wide spectrum of metabolites in combination highlighted 30 metabolites that changed its concentration after NC. The analysis displayed similar changes for purine nucleotide and glutathione as reported previously in another animal model of axonal injury and detected multiple metabolites that increased after the injury. After studying the specificity of the identified metabolites to RGCs in histological sections using imaging mass spectrometry, two metabolites, i.e., L-acetylcarnitine and phosphatidylcholine were increased not only preceding the peak of RGC death in the whole retina but also at the RGC layer (2.3-fold and 1.2-fold, respectively). These phospholipids propose novel mechanisms of RGC death and may serve as early biomarkers of axonal injury. The combinatory metabolomics analyses promise to illuminate pathomechanisms, reveal biomarkers, and allow the discovery of new therapeutic targets of glaucoma.

  39. 自己評価による睡眠の質と関連した、睡眠中の手首運動の定量的特性(Quantitative characterization of wrist movements during sleep in relation to self-rating sleep quality)

    Choilek Siwalee, Motoike Ikuko N., Uchibayashi Toshihiro, Karashima Akihiro, Katayama Norihiro, Nakao Mitsuyuki

    Sleep and Biological Rhythms 16 (4) 480-480 2018年10月

    出版者・発行元:(一社)日本睡眠学会

    ISSN:1446-9235

    eISSN:1479-8425

  40. Regional genetic differences among Japanese populations and performance of genotype imputation using whole-genome reference panel of the Tohoku Medical Megabank Project 国際誌 査読有り

    Jun Yasuda, Fumiki Katsuoka, Inaho Danjoh, Yosuke Kawai, Kaname Kojima, Masao Nagasaki, Sakae Saito, Yumi Yamaguchi-Kabata, Shu Tadaka, Ikuko N. Motoike, Kazuki Kumada, Mika Sakurai-Yageta, Osamu Tanabe, Nobuo Fuse, Gen Tamiya, Koichiro Higasa, Fumihiko Matsuda, Nobufumi Yasuda, Motoki Iwasaki, Makoto Sasaki, Atsushi Shimizu, Kengo Kinoshita, Masayuki Yamamoto

    BMC Genomics 19 (1) 551-551 2018年7月24日

    DOI: 10.1186/s12864-018-4942-0  

    eISSN:1471-2164

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    © 2018 The Author(s). Background: Genotype imputation from single-nucleotide polymorphism (SNP) genotype data using a haplotype reference panel consisting of thousands of unrelated individuals from populations of interest can help to identify strongly associated variants in genome-wide association studies. The Tohoku Medical Megabank (TMM) project was established to support the development of precision medicine, together with the whole-genome sequencing of 1070 human genomes from individuals in the Miyagi region (Northeast Japan) and the construction of the 1070 Japanese genome reference panel (1KJPN). Here, we investigated the performance of 1KJPN for genotype imputation of Japanese samples not included in the TMM project and compared it with other population reference panels. Results: We found that the 1KJPN population was more similar to other Japanese populations, Nagahama (south-central Japan) and Aki (Shikoku Island), than to East Asian populations in the 1000 Genomes Project other than JPT, suggesting that the large-scale collection (more than 1000) of Japanese genomes from the Miyagi region covered many of the genetic variations of Japanese in mainland Japan. Moreover, 1KJPN outperformed the phase 3 reference panel of the 1000 Genomes Project (1KGPp3) for Japanese samples, and IKJPN showed similar imputation rates for the TMM and other Japanese samples for SNPs with minor allele frequencies (MAFs) higher than 1%. Conclusions: 1KJPN covered most of the variants found in the samples from areas of the Japanese mainland outside the Miyagi region, implying 1KJPN is representative of the Japanese population's genomes. 1KJPN and successive reference panels are useful genome reference panels for the mainland Japanese population. Importantly, the addition of whole genome sequences not included in the 1KJPN panel improved imputation efficiencies for SNPs with MAFs under 1% for samples from most regions of the Japanese archipelago.

  41. Omics research project on prospective cohort studies from the Tohoku Medical Megabank Project 国際誌 査読有り

    Seizo Koshiba, Ikuko Motoike, Daisuke Saigusa, Jin Inoue, Matsuyuki Shirota, Yasutake Katoh, Fumiki Katsuoka, Inaho Danjoh, Atsushi Hozawa, Shinichi Kuriyama, Naoko Minegishi, Masao Nagasaki, Takako Takai-Igarashi, Soichi Ogishima, Nobuo Fuse, Shigeo Kure, Gen Tamiya, Osamu Tanabe, Jun Yasuda, Kengo Kinoshita, Masayuki Yamamoto

    Genes to Cells 23 (6) 406-417 2018年6月

    DOI: 10.1111/gtc.12588  

    ISSN:1356-9597

    eISSN:1365-2443

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    © 2018 The Authors. Genes to Cells published by Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd. Population-based prospective cohort studies are indispensable for modern medical research as they provide important knowledge on the influences of many kinds of genetic and environmental factors on the cause of disease. Although traditional cohort studies are mainly conducted using questionnaires and physical examinations, modern cohort studies incorporate omics and genomic approaches to obtain comprehensive physical information, including genetic information. Here, we report the design and midterm results of multi-omics analysis on population-based prospective cohort studies from the Tohoku Medical Megabank (TMM) Project. We have incorporated genomic and metabolomic studies in the TMM cohort study as both metabolome and genome analyses are suitable for high-throughput analysis of large-scale cohort samples. Moreover, an association study between the metabolome and genome show that metabolites are an important intermediate phenotype connecting genetic and lifestyle factors to physical and pathologic phenotypes. We apply our metabolome and genome analyses to large-scale cohort samples in the following studies.

  42. Evaluation of reported pathogenic variants and their frequencies in a Japanese population based on a whole-genome reference panel of 2049 individuals article 国際誌 査読有り

    Yumi Yamaguchi-Kabata, Jun Yasuda, Osamu Tanabe, Yoichi Suzuki, Hiroshi Kawame, Nobuo Fuse, Masao Nagasaki, Yosuke Kawai, Kaname Kojima, Fumiki Katsuoka, Sakae Saito, Inaho Danjoh, Ikuko N. Motoike, Riu Yamashita, Seizo Koshiba, Daisuke Saigusa, Gen Tamiya, Shigeo Kure, Nobuo Yaegashi, Yoshio Kawaguchi, Fuji Nagami, Shinichi Kuriyama, Junichi Sugawara, Naoko Minegishi, Atsushi Hozawa, Soichi Ogishima, Hideyasu Kiyomoto, Takako Takai-Igarashi, Kengo Kinoshita, Masayuki Yamamoto

    Journal of Human Genetics 63 (2) 213-230 2018年2月1日

    DOI: 10.1038/s10038-017-0347-1  

    ISSN:1434-5161

    eISSN:1435-232X

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    © 2017 The Japan Society of Human Genetics. Clarifying allele frequencies of disease-related genetic variants in a population is important in genomic medicine; however, such data is not yet available for the Japanese population. To estimate frequencies of actionable pathogenic variants in the Japanese population, we examined the reported pathological variants in genes recommended by the American College of Medical Genetics and Genomics (ACMG) in our reference panel of genomic variations, 2KJPN, which was created by whole-genome sequencing of 2049 individuals of the resident cohort of the Tohoku Medical Megabank Project. We searched for pathogenic variants in 2KJPN for 57 autosomal ACMG-recommended genes responsible for 26 diseases and then examined their frequencies. By referring to public databases of pathogenic variations, we identified 143 reported pathogenic variants in 2KJPN for the 57 ACMG recommended genes based on a classification system. At the individual level, 21% of the individuals were found to have at least one reported pathogenic allele. We then conducted a literature survey to review the variants and to check for evidence of pathogenicity. Our results suggest that a substantial number of people have reported pathogenic alleles for the ACMG genes, and reviewing variants is indispensable for constructing the information infrastructure of genomic medicine for the Japanese population.

  43. JMorp: Japanese Multi Omics Reference Panel 国際誌 査読有り

    Shu Tadaka, Daisuke Saigusa, Ikuko N. Motoike, Jin Inoue, Yuichi Aoki, Matsuyuki Shirota, Seizo Koshiba, Masayuki Yamamoto, Kengo Kinoshita

    Nucleic Acids Research 46 (D1) D551-D557 2018年1月1日

    DOI: 10.1093/nar/gkx978  

    ISSN:0305-1048

    eISSN:1362-4962

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    © 2017 The Author(s). We developed jMorp, a new database containing metabolome and proteome data for plasma obtained from >5000 healthy Japanese volunteers from the Tohoku Medical Megabank Cohort Study, which is available at https://jmorp.megabank.tohoku. ac.jp. Metabolome data were measured by proton nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry (LC-MS), while proteome data were obtained by nanoLC-MS. We released the concentration distributions of 37 metabolites identified by NMR, distributions of peak intensities of 257 characterized metabolites by LC-MS, and observed frequencies of 256 abundant proteins. Additionally, correlation networks for the metabolites can be observed using an interactive network viewer. Compared with some existing databases, jMorp has some unique features: (i) Metabolome data were obtained using a single protocol in a single institute, ensuring that measurement biases were significantly minimized; (ii) The database contains large-scale data for healthy volunteers with various health records and genome data and (iii) Correlations between metabolites can be easily observed using the graphical viewer. Metabolites data are becoming important intermediate markers for evaluating the health states of humans, and thus jMorp is an outstanding resource for a wide range of researchers, particularly those in the fields of medical science, applied molecular biology, and biochemistry.

  44. The structural origin of metabolic quantitative diversity 国際誌 査読有り

    Seizo Koshiba, Ikuko Motoike, Kaname Kojima, Takanori Hasegawa, Matsuyuki Shirota, Tomo Saito, Daisuke Saigusa, Inaho Danjoh, Fumiki Katsuoka, Soichi Ogishima, Yosuke Kawai, Yumi Yamaguchi-Kabata, Miyuki Sakurai, Sachiko Hirano, Junichi Nakata, Hozumi Motohashi, Atsushi Hozawa, Shinichi Kuriyama, Naoko Minegishi, Masao Nagasaki, Takako Takai-Igarashi, Nobuo Fuse, Hideyasu Kiyomoto, Junichi Sugawara, Yoichi Suzuki, Shigeo Kure, Nobuo Yaegashi, Osamu Tanabe, Kengo Kinoshita, Jun Yasuda, Masayuki Yamamoto

    Scientific Reports 6 31463-31463 2016年8月16日

    出版者・発行元:NATURE PUBLISHING GROUP

    DOI: 10.1038/srep31463  

    ISSN:2045-2322

    eISSN:2045-2322

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    © The Author(s) 2016. Relationship between structural variants of enzymes and metabolic phenotypes in human population was investigated based on the association study of metabolite quantitative traits with whole genome sequence data for 512 individuals from a population cohort. We identified five significant associations between metabolites and non-synonymous variants. Four of these non-synonymous variants are located in enzymes involved in metabolic disorders, and structural analyses of these moderate non-synonymous variants demonstrate that they are located in peripheral regions of the catalytic sites or related regulatory domains. In contrast, two individuals with larger changes of metabolite levels were also identified, and these individuals retained rare variants, which caused non-synonymous variants located near the catalytic site. These results are the first demonstrations that variant frequency, structural location, and effect for phenotype correlate with each other in human population, and imply that metabolic individuality and susceptibility for diseases may be elicited from the moderate variants and much more deleterious but rare variants.

  45. Establishment of protocols for global metabolomics by LC-MS for biomarker discovery 国際誌 査読有り

    Daisuke Saigusa, Yasunobu Okamura, Ikuko N. Motoike, Yasutake Katoh, Yasuhiro Kurosawa, Reina Saijyo, Seizo Koshiba, Jun Yasuda, Hozumi Motohashi, Junichi Sugawara, Osamu Tanabe, Kengo Kinoshita, Masayuki Yamamoto

    PLoS ONE 11 (8) e0160555 2016年8月

    出版者・発行元:PUBLIC LIBRARY SCIENCE

    DOI: 10.1371/journal.pone.0160555  

    ISSN:1932-6203

    eISSN:1932-6203

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    © 2016 Saigusa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Metabolomics is a promising avenue for biomarker discovery. Although the quality of metabolomic analyses, especially global metabolomics (G-Met) using mass spectrometry (MS), largely depends on the instrumentation, potential bottlenecks still exist at several basic levels in the metabolomics workflow. Therefore, we established a precise protocol initially for the G-Met analyses of human blood plasma to overcome some these difficulties. In our protocol, samples are deproteinized in a 96-well plate using an automated liquid-handling system, and conducted either using a UHPLC-QTOF/MS system equipped with a reverse phase column or a LC-FTMS system equipped with a normal phase column. A normalization protocol of G-Met data was also developed to compensate for intra- and inter-batch differences, and the variations were significantly reduced along with our normalization, especially for the UHPLC-QTOF/MS data with a C18 reverse-phase column for positive ions. Secondly, we examined the changes in metabolomic profiles caused by the storage of EDTA-blood specimens to identify quality markers for the evaluation of the specimens' preanalytical conditions. Forty quality markers, including lysophospholipids, dipeptides, fatty acids, succinic acid, amino acids, glucose, and uric acid were identified by G-Met for the evaluation of plasma sample quality and established the equation of calculating the quality score. We applied our quality markers to a small-scale study to evaluate the quality of clinical samples. The G-Met protocols and quality markers established here should prove useful for the discovery and development of biomarkers for a wider range of diseases.

  46. Validation of multiple single nucleotide variation calls by additional exome analysis with a semiconductor sequencer to supplement data of whole-genome sequencing of a human population 国際誌 査読有り

    Ikuko N. Motoike, Mitsuyo Matsumoto, Inaho Danjoh, Fumiki Katsuoka, Kaname Kojima, Naoki Nariai, Yukuto Sato, Yumi Yamaguchi-Kabata, Shin Ito, Hisaaki Kudo, Ichiko Nishijima, Satoshi Nishikawa, Xiaoqing Pan, Rumiko Saito, Sakae Saito, Tomo Saito, Matsuyuki Shirota, Kaoru Tsuda, Junji Yokozawa, Kazuhiko Igarashi, Naoko Minegishi, Osamu Tanabe, Nobuo Fuse, Masao Nagasaki, Kengo Kinoshita, Jun Yasuda, Masayuki Yamamoto

    BMC Genomics 15 (1) 673-673 2014年8月10日

    出版者・発行元:BIOMED CENTRAL LTD

    DOI: 10.1186/1471-2164-15-673  

    ISSN:1471-2164

    eISSN:1471-2164

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    © 2014 Motoike et al.; licensee BioMed Central Ltd. Background: Validation of single nucleotide variations in whole-genome sequencing is critical for studying disease-related variations in large populations. A combination of different types of next-generation sequencers for analyzing individual genomes may be an efficient means of validating multiple single nucleotide variations calls simultaneously.Results: Here, we analyzed 12 independent Japanese genomes using two next-generation sequencing platforms: the Illumina HiSeq 2500 platform for whole-genome sequencing (average depth 32.4×), and the Ion Proton semiconductor sequencer for whole exome sequencing (average depth 109×). Single nucleotide polymorphism (SNP) calls based on the Illumina Human Omni 2.5-8 SNP chip data were used as the reference. We compared the variant calls for the 12 samples, and found that the concordance between the two next-generation sequencing platforms varied between 83% and 97%.Conclusions: Our results show the versatility and usefulness of the combination of exome sequencing with whole-genome sequencing in studies of human population genetics and demonstrate that combining data from multiple sequencing platforms is an efficient approach to validate and supplement SNP calls.

  47. Global genetic response in a cancer cell: Self-organized coherent expression dynamics 国際誌 査読有り

    Masa Tsuchiya, Midori Hashimoto, Yoshiko Takenaka, Ikuko N. Motoike, Kenichi Yoshikawa

    PLoS ONE 9 (5) e97411 2014年5月15日

    出版者・発行元:PUBLIC LIBRARY SCIENCE

    DOI: 10.1371/journal.pone.0097411  

    ISSN:1932-6203

    eISSN:1932-6203

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    Understanding the basic mechanism of the spatio-temporal self-control of genome-wide gene expression engaged with the complex epigenetic molecular assembly is one of major challenges in current biological science. In this study, the genome-wide dynamical profile of gene expression was analyzed for MCF-7 breast cancer cells induced by two distinct ErbB receptor ligands: epidermal growth factor (EGF) and heregulin (HRG), which drive cell proliferation and differentiation, respectively. We focused our attention to elucidate how global genetic responses emerge and to decipher what is an underlying principle for dynamic self-control of genome-wide gene expression. The whole mRNA expression was classified into about a hundred groups according to the root mean square fluctuation ( rmsf). These expression groups showed characteristic time-dependent correlations, indicating the existence of collective behaviors on the ensemble of genes with respect to mRNA expression and also to temporal changes in expression. All-or-none responses were observed for HRG and EGF (biphasic statistics) at around 10-20 min. The emergence of time-dependent collective behaviors of expression occurred through bifurcation of a coherent expression state (CES). In the ensemble of mRNA expression, the self-organized CESs reveals distinct characteristic expression domains for biphasic statistics, which exhibits notably the presence of criticality in the expression profile as a route for genomic transition. In time-dependent changes in the expression domains, the dynamics of CES reveals that the temporal development of the characteristic domains is characterized as autonomous bistable switch, which exhibits dynamic criticality (the temporal development of criticality) in the genome-wide coherent expression dynamics. It is expected that elucidation of the biophysical origin for such critical behavior sheds light on the underlying mechanism of the control of whole genome. © 2014 Tsuchiya et al.

  48. COXPRESdb: A database of comparative gene coexpression networks of eleven species for mammals 国際誌 査読有り

    Takeshi Obayashi, Yasunobu Okamura, Satoshi Ito, Shu Tadaka, Ikuko N. Motoike, Kengo Kinoshita

    Nucleic Acids Research 41 (D1) D1014-20-D1020 2013年1月1日

    DOI: 10.1093/nar/gks1014  

    ISSN:0305-1048

    eISSN:1362-4962

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    Coexpressed gene databases are valuable resources for identifying new gene functions or functional modules in metabolic pathways and signaling pathways. Although coexpressed gene databases are a fundamental platform in the field of plant biology, their use in animal studies is relatively limited. The COXPRESdb (http://coxpresdb.jp) provides coexpression relationships for multiple animal species, as comparisons of coexpressed gene lists can enhance the reliability of gene coexpression determinations. Here, we report the updates of the database, mainly focusing on the following two points. First, we updated our coexpression data by including recent microarray data for the previous seven species (human, mouse, rat, chicken, fly, zebrafish and nematode) and adding four new species (monkey, dog, budding yeast and fission yeast), along with a new human microarray platform. A reliability scoring function was also implemented, based on coexpression conservation to filter out coexpression with low reliability. Second, the network drawing function was updated, to implement automatic cluster analyses with enrichment analyses in Gene Ontology and in cis elements, along with interactive network analyses with Cytoscape Web. With these updates, COXPRESdb will become a more powerful tool for analyses of functional and regulatory networks of genes in a variety of animal species. © The Author(s) 2012.

  49. Dendritic gates for signal integration with excitability-dependent responsiveness 国際誌 査読有り

    Hisako Takigawa-Imamura, Ikuko N. Motoike

    Neural Networks 24 (10) 1143-1152 2011年12月

    出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD

    DOI: 10.1016/j.neunet.2011.05.003  

    ISSN:0893-6080

    eISSN:1879-2782

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    The shape and excitability of neuronal dendrites are expected to be responsible for the functional characteristics of information processing in the brain. In the present study, we proposed that excitable media with branching patterns mimicked the multi-signal integration of neuronal computation. We initially examined the conditions of the coincidence detection of two inputs as the simplest form of signal integration. We considered a gate with two channels that was bound by a circular joint with uniform excitability and demonstrated that the time window for the coincidence detection was controlled by the geometry and excitability of the gate. The functions of the gate were due to the unique property of the excitation waves, known as the curvature effect. The expanded spatial spread diluted the incoming excitation signals to insufficient levels to sustain wave advancement. Next, we applied dendritic gates that were reminiscent of neuronal dendrites for multi-signal integration. The irregular dendritic patterns were produced by a cellular automaton model of self-organizing pattern formation that adopted the semi-random grid in numerical simulations. We demonstrated that the threshold operation for multiple inputs was conducted by the dendritic pattern. The thresholds varied among gates owing to their irregular patterns, and were adjusted by changing the excitability without changing the gate geometry. The materializable model may provide a novel biomimetic approach for developing fuzzy hardware with adjustable responsiveness. © 2011 Elsevier Ltd.

  50. Density wave propagation of a wave train in a closed excitable medium 国際誌 査読有り

    Nobuhiko J. Suematsu, Taisuke Sato, Ikuko N. Motoike, Kenji Kashima, Satoshi Nakata

    Physical Review E - Statistical, Nonlinear, and Soft Matter Physics 84 (4) 046203-046203 2011年10月5日

    出版者・発行元:AMER PHYSICAL SOC

    DOI: 10.1103/PhysRevE.84.046203  

    ISSN:1539-3755

    eISSN:1550-2376

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    A wave train in an excitable reaction-diffusion medium shows a variety of spatiotemporal patterns as a result of interactions between the individual waves. In this paper, we report a novel spatiotemporal pattern in a wave train in a closed excitable medium. We carried out experiments using a photosensitive Belousov-Zhabotinsky reaction with Ru(bpy)32+ as a catalyst and a numerical calculation using the FitzHugh-Nagumo equation. A wave train was locally distributed as an initial condition and the number of waves was systematically varied. In both the experiment and numerical calculation, density wave propagation was formed in a wave train during relaxation with a large number of waves. Our results suggest that density wave propagation originates from inhibitory interaction between the waves. © 2011 American Physical Society.

  51. Self-organizing striped and spotted patterns on a discrete reaction-diffusion model 査読有り

    浅井 哲也, 元池 N. 育子

    Nonlinear Theory and Its Applications 2 (3) 363-371 2011年7月1日

    出版者・発行元:一般社団法人 電子情報通信学会

    DOI: 10.1588/nolta.2.363  

    ISSN:2185-4106

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    We propose a novel and simple discrete reaction-diffusion model that self-organizes striped and spotted spatial patterns. Through theoretical analyses, we show that the spatial frequency of the generated patterns is proportional to diffusion length. Through extensive numerical simulations, we demonstrate that the model can produce Turing-like striped and spotted spatial patterns.

  52. Branching pattern formation that reflects the history of signal propagation. 国際誌 査読有り

    Ikuko N Motoike, Hisako Takigawa-Imamura

    Physical review. E, Statistical, nonlinear, and soft matter physics 82 (4 Pt 2) 046205-046205 2010年10月

    DOI: 10.1103/PhysRevE.82.046205  

    ISSN:1550-2376 1539-3755

    eISSN:1550-2376

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    In living organisms, branching structures are often observed in open systems. During the process of structure formation/deformation, signal propagation can be observed. Branching paths often deform depending on the history of signal propagation. To gain a better understanding of the process of pattern formation that results in characteristic geometrical paths, we adopt a system in which the dynamics of path formation are correlated with signal propagation. This model involves both branch-generation dynamics and signal-propagation dynamics, and we introduced positive feedback between these two dynamic processes. We studied the geometrical properties of path deformation and the pattern of signal propagation using a discretized reaction-diffusion model. The proposed model can qualitatively reproduce different branching patterns and means of signal propagation. One remarkable result is that the mutual interaction of these two dynamic processes leads to autonomous wave generation, similar to a pacemaker or the generation of spiral waves. Because the autonomous wave generation in the signal is spontaneous, the shapes of the branching paths become distorted. We discuss the correlation between path deformation and signal propagation as a first step in understanding signal processing for such complex deformable paths.

  53. Apex of a V-shaped cut field acts as a pacemaker on an oscillatory system

    Ikuko N. Motoike, Satoshi Nakata, Yasutaka Iguchi, Kaori K. Takemura, Kumiko Hayashi, Kenichi Yoshikawa

    CHEMICAL PHYSICS LETTERS 490 (4-6) 238-241 2010年4月

    出版者・発行元:ELSEVIER SCIENCE BV

    DOI: 10.1016/j.cplett.2010.03.046  

    ISSN:0009-2614

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    The generation and propagation of chemical waves in the Belousov-Zhabotinsky (BZ) reaction were investigated using a cation-exchange membrane embedded with a metal catalyst as a 2-dimensional oscillatory/active field. We found that a target pattern is generated from the top of a V-shape, indicating that the apex on the boundary between active and passive fields behaves as a pacemaker. A Plausible mechanism for this phenomenon is proposed based on a reaction-diffusion equation. (C) 2010 Published by Elsevier B.V.

  54. Image Processing with Neuron-Like Branching Elements (POSTER) 査読有り

    Hisako Takigawa-Imamura, Ikuko N. Motoike

    UNCONVENTIONAL COMPUTATION, PROCEEDINGS 6079 194-194 2010年

    出版者・発行元:SPRINGER-VERLAG BERLIN

    ISSN:0302-9743

  55. 反応拡散場の非一様性を活用した多値演算/ Multi-Valued Operations with an Inhomogeneous Reaction-Diffusion Field 査読有り

    元池N.育子

    Journal of Computer Chemistry, Japan 9 (3) 121-126 2010年

    出版者・発行元:Society of Computer Chemistry, Japan

    DOI: 10.2477/jccj.H2116  

    ISSN:1347-1767 1347-3824

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    空間的な広がりを持つ場の化学反応を記述する方式に, 反応拡散モデルがある. このモデルはこれまで主に時空間パターンの再現などの観点から研究されてきた. 近年, 生物の信号処理が生体内, つまり溶液系で行われていることなどから, 従来型の信号処理機構ではなく, 反応拡散の性質を活用した, 新しいタイプの信号処理モデルが模索されてきている. 反応拡散場上の興奮波の伝播を信号の伝播ととらえる立場にたち, 反応場の性質を非一様にすることで, 時間情報を含んだ信号処理が実装可能となることを, 著者らはこれまで示してきた.拡散場上に, 二つの入力信号の伝播する反応拡散場と, 出力信号の伝播する反応拡散場を配置することで, 二入力信号の入力タイミングの同期を検出することが可能であることが, 数値計算・化学反応実験でこれまで示されている. 本論文では, 出力場の先端部分に, 生物由来のバースティングを示す性質を付加することで, 二つの信号の入力時間差が, 出力場における応答波数で符号化され, 多値演算の形で実装可能であることを報告する.

  56. Towards Computation in Noisy Reaction-Diffusion Cellular Automata 査読有り

    Hisako Takigawa-Imamura, Ikuko N. Motoike

    2009 INTERNATIONAL SYMPOSIUM ON INTELLIGENT SIGNAL PROCESSING AND COMMUNICATION SYSTEMS (ISPACS 2009) 355-358 2009年

    出版者・発行元:IEEE

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    A cellular automaton model proposed by Motoike includes reaction-diffusion dynamics in a simple manner (Motoike, J. Phys. Soc. Jpn. 2007). The semi-random grid adopted in this model is designed to describe biological phenomena that involve intrinsic fluctuations. It has been shown that this model can exhibit branching patterns reminiscent of neural dendrites, whose formation may be regulated by excitation signals as suggested by experimental results. From a computational viewpoint, a random grid can be regarded as representing intrinsic spatial noise. In this study, we firstly compared the features of the patterns obtained from numerical simulations using regular and semi-random square grids. It was demonstrated that the directions of the path growth tended to be orthogonal or parallel to the grid owing to the anisotropy of the regular grid. We found that, as the parameter values are varied, the numbers of endpoints change continuously for patterns exhibited by a semi-random grid, whereas, they change discontinuously for a regular grid. Next, we investigated the patterns of path formation when excitation signals were added at spatially random points. The patterns obtained under these conditions exhibited highly complex and random shapes of branches. It was also revealed that the patterns in the case of random inputs have endpoints that are more numerous than in the case of a spatially fixed input. This result suggested that the patterns represent the history of the spatial history of excitation signal inputs.

  57. Basic Information Processing Operations with Pulses of Excitation in a Reaction-Diffusion System 査読有り

    K. Yoshikawa, I. N. Motoike, T. Ichino, T. Yamaguchi, Y. Igarashi, J. Gorecki, J. N. Gorecka

    INTERNATIONAL JOURNAL OF UNCONVENTIONAL COMPUTING 5 (1) 3-37 2009年

    出版者・発行元:OLD CITY PUBLISHING INC

    ISSN:1548-7199

    eISSN:1548-7202

    詳細を見る 詳細を閉じる

    In the paper we present some of the ideas that can be used for applications of spatially distributed excitable chemical medium in information processing. We describe a number of devices that perform basic operations on information coded in pulses of excitation like signal diodes, logical gates, signal comparers and pulse counters. The perspectives for the further development of this branch Of unconventional computing are discussed.

  58. Single-electron circuits performing dendritic pattern formation with nature-inspired cellular automata 査読有り

    Takahide Oya, Ikuko N. Motoike, Tetsuya Asai

    INTERNATIONAL JOURNAL OF BIFURCATION AND CHAOS 17 (10) 3651-3655 2007年10月

    出版者・発行元:WORLD SCIENTIFIC PUBL CO PTE LTD

    DOI: 10.1142/S0218127407019512  

    ISSN:0218-1274

    詳細を見る 詳細を閉じる

    We propose a novel semiconductor device in which electronic-analogue dendritic trees grow on multilayer single-electron circuits. A simple cellular-automaton circuit was designed for generating dendritic patterns by utilizing the physical properties of single-electron devices, i.e. quantum and thermal effects in tunneling junctions. We demonstrate typical operations of the proposed circuit through extensive numerical simulations.

  59. Simple modeling of branching pattern formation in a reaction diffusion system with cellular automaton 査読有り

    Ikuko N. Motoike

    JOURNAL OF THE PHYSICAL SOCIETY OF JAPAN 76 (3) 1-34002 2007年3月

    出版者・発行元:PHYSICAL SOC JAPAN

    DOI: 10.1143/JPSJ.76.034002  

    ISSN:0031-9015

    詳細を見る 詳細を閉じる

    In the present paper, I propose a simple generic discretized model for the formation of various patterns based on a reaction-diffusion model of the growth patterns of bacterial colonies. Bacterial colonies show several patterns, with a characteristic pattern being a branching dendritic one with various branch densities. In addition to living systems, these branching patterns can also be observed in physical and chemical systems. Several reaction-diffusion models have been proposed to describe their formation. The model proposed here is a simplified discretized one based on previous models and involves three variables; namely, activators, inactivators, and the substrate. By changing only the mobility of the activators and the initial substrate, the proposed model can reproduce different patterns that are based on the branching patterns. I also investigate the characteristics of the shape and growth rate of the pattern formation.

  60. A reaction-diffusion model performing stripe- and spot-image restoration and its LSI implementation 査読有り

    Yohei Suzuki, Takahiro Takayama, Ikuko N. Motoike, Tetsuya Asai

    ELECTRONICS AND COMMUNICATIONS IN JAPAN PART III-FUNDAMENTAL ELECTRONIC SCIENCE 90 (1) 20-29 2007年

    出版者・発行元:SCRIPTA TECHNICA-JOHN WILEY & SONS

    DOI: 10.1002/ecjc.20243  

    ISSN:1042-0967

    詳細を見る 詳細を閉じる

    This paper is intended to develop an LSI that restores in real time an image pattern with defects and contamination. To this end, based on the principle of shape formation in biological bodies, a reaction-diffusion model that can generate and repair Turing patterns, such as stripes and spots seen in fingerprint and body marks, is proposed. A parallel architecture of the reaction-diffusion chips incorporating this model is presented. By means of circuit simulation, it is shown that this LSI can restore stripe (spot) patterns. (C) 2006 Wiley Periodicals, Inc.

  61. Striped and spotted pattern generation on reaction-diffusion cellular automata - Theory and LSI implementation 査読有り

    Youhei Suzuki, Takahiro Takayama, Ikuko N. Motoike, Tetsuya Asai

    INTERNATIONAL JOURNAL OF UNCONVENTIONAL COMPUTING 3 (1) 1-13 2007年

    出版者・発行元:OLD CITY PUBLISHING INC

    ISSN:1548-7199

    詳細を見る 詳細を閉じる

    A novel reaction-diffusion cellular-automaton model that generates Turing like spatial patterns is proposed. The model employs linear diffusion fields of activators and inhibitors and a discrete transition rule after diffusion. Theoretical analysis of the one dimensional model proved that i) spatial distribution given by a periodic square function is stable at the equilibrium and ii) the spatial frequency is inversely proportional to the square root of a diffusion coefficient of the inhibitors. We also designed LSI circuits that implement the RD model on a silicon chip that has a compact construction and low-power consumption. Circuit simulations revealed that the proposed LSIs could restore stripe and spot images in a short time regardless of the number of pixels in the image.

  62. Design methodologies for compact logic circuits based on collision-based computing 査読有り

    Kazuhito Yamada, Ikuko N. Motoike, Tetsuya Asai, Yoshihito Amemiya

    IEICE ELECTRONICS EXPRESS 3 (13) 292-298 2006年7月

    出版者・発行元:IEICE-INST ELECTRONICS INFORMATION COMMUNICATIONS ENG

    DOI: 10.1587/elex.3.292  

    ISSN:1349-2543

    詳細を見る 詳細を閉じる

    A method of designing compact multiple-input combinational logic circuits is proposed. We show that i) fundamental logic gates can be constructed by a small number of collision-based fusion gates, ii) multiple-input logic gates are constructed in a systematic manner, iii) the number of transistors in specific logic gates constructed by the proposed method is significantly smaller than that of conventional logic gates.

  63. 縞・斑点画像パターンの修復を行う反応拡散モデルとそのLSI化 査読有り

    鈴木 洋平, 高山 貴裕, 元池 N. 育子, 浅井 哲也

    電子情報通信学会論文誌A J87-A (11) 1272-1281 2005年11月1日

    出版者・発行元:一般社団法人電子情報通信学会

    DOI: 10.1587/transfun.J87.A.1272  

    ISSN:0913-5707

    詳細を見る 詳細を閉じる

    本論文は, 欠損や汚れのある画像パターンをリアルタイムに修復するLSIの開発を目指したものである. そのために, 生物の形づくりの原理に基づいて, 指紋や体模様に見られるしま・斑点などのTuringパターンを生成・修復する反応拡散モデルを提案する. その後, そのモデルを実装する反応拡散チップの並列アーキテクチャを提案する. 回路シミュレーションにより, このLSIがしま(斑点)パターンを復元できることを示す.

  64. Three-valued logic gates in reaction-diffusion excitable media 査読有り

    IN Motoike, A Adarnatzky

    CHAOS SOLITONS & FRACTALS 24 (1) 107-114 2005年4月

    出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD

    DOI: 10.1016/j.chaos.2004.07.021  

    ISSN:0960-0779

    詳細を見る 詳細を閉じる

    It is well established now that excitable media are capable of implementing of a wide range of computational operations, from image processing to logical computation to navigation of robots. The findings published so far in the field of logical computation were concerned solely with realization of boolean logic. This imposed somewhat artificial limitations on a suitability of excitable media for logical reasoning and restricted a range of possible applications of these non-classical computational devices in the field of artificial intelligence. In the paper we go beyond binary logic and show how to implement three-valued logical operations in toy models of geometrically constrained excitable media. We realize several types of logical gates, including Lukasiewicz conjunction and disjunction, and Sobocinski conjunction in cellular automata and FitzHugh-Nagumo models of T-shaped excitable media. (C) 2004 Elsevier Ltd. All rights reserved.

  65. 1P311 信号伝播に作用される離散反応拡散系での樹状形状形成(数理生物学))

    元池 育子

    生物物理 45 S109 2005年

    出版者・発行元:一般社団法人 日本生物物理学会

    DOI: 10.2142/biophys.45.S109_3  

  66. Information operations with multiple pulses on an excitable field 査読有り

    Ikuko N. Motoike, Kenichi Yoshikawa

    Chaos, Solitons and Fractals 17 (2-3) 455-461 2003年7月

    DOI: 10.1016/S0960-0779(02)00388-0  

    ISSN:0960-0779

    詳細を見る 詳細を閉じる

    Recently, we proposed a novel strategy for information operations on an excitable field, where, by adopting a suitable geometry for the excitable field, time-sequential input was processed with logical operations, co-incidence detection and real-time memorization. The present paper describes the advancement of this strategy for computation with multiple excitable pulses. We show a spatial arrangement for detecting the interval between successive pulses in other words, the output pulse is generated only where the time-difference between input pulses falls within a suitable range. We also show some examples of multiple-valued operations of comparison and subtraction of the input strength, where the pulse number scales with the input strength. © 2002 Elsevier Science Ltd. All rights reserved.

  67. Different operations on a single circuit: Field computation on an excitable chemical system 査読有り

    T Ichino, Y Igarashi, IN Motoike, K Yoshikawa

    JOURNAL OF CHEMICAL PHYSICS 118 (18) 8185-8190 2003年5月

    出版者・発行元:AMER INST PHYSICS

    DOI: 10.1063/1.1565103  

    ISSN:0021-9606

    詳細を見る 詳細を閉じる

    Recently, it has been proposed that various kinds of time operations can be performed using an excitable field, mainly based on computer simulation. In this study, we performed experiments toward the realization of a time operation, such as time-difference detection. We used the photosensitive Belousov-Zhabotinsky reaction as a spatially distributed excitable field. We found that a single geometrical circuit can perform different operations with changes in the intensity of light illumination. The experimental results are discussed in relation to the idea of a non-Neumann-type computational device. (C) 2003 American Institute of Physics.

  68. 3G1515 興奮場の幾何学形状特性と信号伝播について(24.数理生物学,一般講演,日本生物物理学会第40回年会)

    元池 育子

    生物物理 42 (2) S167 2002年

    出版者・発行元:一般社団法人 日本生物物理学会

    DOI: 10.2142/biophys.42.S167_1  

  69. 2P227興奮場の幾何学形状特性を用いた情報伝達・処理

    元池 育子

    生物物理 41 S152 2001年

    出版者・発行元:一般社団法人 日本生物物理学会

    DOI: 10.2142/biophys.41.S152_3  

  70. Real-time memory on an excitable field 査読有り

    Ikuko N. Motoike, Kenichi Yoshikawa, Yasutaka Iguchi, Satoshi Nakata

    Physical Review E - Statistical, Nonlinear, and Soft Matter Physics 63 (3) 362201-362204 2001年

    DOI: 10.1103/PhysRevE.63.036220  

    ISSN:1539-3755

    詳細を見る 詳細を閉じる

    A method for computing logic operations based on the time-sequential information in a geometrically arranged excitable field was extended. A strategy for creating real-time memory was described. Input pulse trains was stored as a sequence of rotating traveling waves in a circular excitable field by using its characteristics as a diode to spatially asymmetric arrangement.

  71. 1G1815 空間的に非対称な興奮場における情報伝達・処理

    元池 育子

    生物物理 40 S57 2000年

    出版者・発行元:一般社団法人 日本生物物理学会

    DOI: 10.2142/biophys.40.S57_2  

    ISSN:0582-4052

  72. Information operations with an excitable field 査読有り

    Ikuko Motoike, Kenichi Yoshikawa

    Physical Review E - Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics 59 (5) 5354-5360 1999年

    DOI: 10.1103/PhysRevE.59.5354  

    ISSN:1063-651X

    詳細を見る 詳細を閉じる

    It is well established that a traveling wave can be generated on an excitable field, which is described with a pair of partial differential equations for an activator and inhibitor. In the present paper, we use a numerical simulation to show that the traveling wave, or signaling pulse, can be transmitted from an excitable field to an opposing excitable field via an intervening passive diffusion field in a characteristic manner depending on the spatial geometry of the excitable fields. Using such characteristics, it is possible to design various kinds of logic gates together with a time-sequential memory device. Thus, these functions can perform time-sensitive operations in the absence of any controlling clock. It may be possible to accomplish these computations with excitable fields in an actual system, or to create a “field computer” composed of electronic active and passive units. © 1999 The American Physical Society.

  73. Logic operation on an excitable field 査読有り

    Motoike, I, K Yoshikawa

    ICONIP'98: THE FIFTH INTERNATIONAL CONFERENCE ON NEURAL INFORMATION PROCESSING JOINTLY WITH JNNS'98: THE 1998 ANNUAL CONFERENCE OF THE JAPANESE NEURAL NETWORK SOCIETY - PROCEEDINGS, VOLS 1-3 720-722 1998年

    出版者・発行元:OHMSHA LTD

    詳細を見る 詳細を閉じる

    To develop novel type of parallel computer by mimicking the essence of actual neural computation in living organisms, we propose a strategy to create logic gates processed on an excitable field. Although considerable efforts have been paid to investigate the principle of natural neural networks in the past several decades, most of the previous studies have ignored, or not considered so much, on the excitable properties of individual neurons. In the present paper we will report the result of simulations with the partial differential equation of FitzHugh-Nagumo type, showing that the diode characteristics is generated on an excitable field intervened by diffusion field, with suitable geometrical arrangement of the excitable field and diffusion field. We will show that logic gates, such as AND, OR, NOT, are created on the excitable field. It is to be noted that one can perform the computation with the logic operations including "time-arrow" in an explicit manner. In the absence of any central clock, time computation such as detection of input time difference is easily performed.

  74. Design of an excitable field towards a novel parallel computation

    K Yoshikawa, Motoike, I, K Kajiya

    IEICE TRANSACTIONS ON ELECTRONICS E80C (7) 931-934 1997年7月

    出版者・発行元:IEICE-INST ELECTRONICS INFORMATION COMMUNICATIONS ENG

    ISSN:0916-8524

    eISSN:1745-1353

    詳細を見る 詳細を閉じる

    A suggestion for creating an excitable/oscillatory field with solid-state material is proposed. Tn essence, the idea is to make a spatial array of ''mesoscopic particles'' with the characteristics of a first-order phase transition. A theoretical computation shows that an auto-wave, or excitable wave, is generated in such an excitable field. A simple example of using this system as a diode in information flow is given.

︎全件表示 ︎最初の5件までを表示

MISC 41

  1. 日本人成人GWASによる肺機能・FeNO関連遺伝子の同定

    山田 充啓, 元池 育子, 小島 要, 光根 歩, 大江 崇, 一ノ瀬 正和, 山本 雅之, 杉浦 久敏

    日本呼吸器学会誌 11 (増刊) 129-129 2022年4月

    出版者・発行元:(一社)日本呼吸器学会

    ISSN:2186-5876

    eISSN:2186-5884

  2. 東北メディカル・メガバンク計画健康調査における眼軸長のゲノムワイド関連解析

    布施 昇男, 櫻井 美由紀, 元池 育子, 小島 要, 平良 摩紀子, 宇留野 晃, 濱中 洋平, 中村 智洋, 荻島 創一, 寳澤 篤, 栗山 進一, 呉 繁夫, 木下 賢吾, 山本 雅之

    日本眼科学会雑誌 126 (臨増) 216-216 2022年3月

    出版者・発行元:(公財)日本眼科学会

    ISSN:0029-0203

  3. Publisher Correction: Enhancer remodeling promotes tumor-initiating activity in NRF2-activated non-small cell lung cancers. 国際誌

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    Nature communications 12 (1) 506-506 2021年1月15日

    DOI: 10.1038/s41467-021-20927-9  

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    小柴生造, 小柴生造, 小柴生造, 元池育子, 元池育子, 三枝大輔, 三枝大輔, 井上仁, 井上仁, 井上仁, 菱沼英史, 青木裕一, 青木裕一, 田高周, 田高周, 城田松之, 城田松之, 城田松之, 木下賢吾, 木下賢吾, 木下賢吾, 山本雅之, 山本雅之, 山本雅之

    日本生化学会大会(Web) 94th 2021年

  5. 非常に規則的な睡眠/覚醒タイミングは健康に密接に関係するか?-睡眠/覚醒間の関連性,客観的な睡眠関連パラメータ,及び主観的睡眠の質に関する定量的研究

    CHOILEK Siwalee, MOTOIKE Ikuko N., UCHIBAYASHI Toshihiro, KARASHIMA Akihiro, KARASHIMA Akihiro, KATAYAMA Norihiro, NAKAO Mitsuyuki

    電子情報通信学会技術研究報告 119 (224(MBE2019 29-44)(Web)) 2019年

    ISSN:0913-5685

  6. 大規模コホート研究におけるGC-MS/MSによるヒト血漿メタボローム解析

    三枝大輔, 三枝大輔, 松川直美, 松川直美, 田高周, 田高周, 元池育子, 元池育子, 小柴生造, 小柴生造

    日本プロテオーム学会誌(Web) 4 (1) 2019年

    ISSN:2432-2776

  7. ゲノミクスを基盤とした生活習慣病解析最前線 ゲノム情報と連携した日本人多層オミックス参照パネルの意義

    小柴 生造, 元池 育子, 三枝 大輔, 井上 仁, 城田 松之, 青木 裕一, 田高 周, 斎藤 智, 木下 賢吾, 山本 雅之

    糖尿病 61 (Suppl.1) S-48 2018年4月

    出版者・発行元:(一社)日本糖尿病学会

    ISSN:0021-437X

    eISSN:1881-588X

  8. Estimating frequency of pathogenic variants in a Japanese population by using the whole-genome reference panel of ToMMo

    Yumi Yamaguchi-Kabata, Jun Yasuda, Osamu Tanabe, Yoichi Suzuki, Hiroshi Kawame, Nobuo Fuse, Masao Nagasaki, Yosuke Kawai, Kaname Kojima, Fumiki Katsuoka, Sakae Saito, Inaho Danjoh, Ikuko N. Motoike, Riu Yamashita, Seizo Koshiba, Daisuke Saigusa, Gen Tamiya, Shigeo Kure, Nobuo Yaegashi, Yoshio Kawaguchi, Fuji Nagami, Shinichi Kuriyama, Junichi Sugawara, Naoko Minegishi, Atsushi Hozawa, Soichi Ogishima, Hideyasu Kiyomoto, Takako Takai-Igarashi, Kengo Kinoshita, Masayuki Yamamoto

    HUMAN GENOMICS 12 2018年3月

    出版者・発行元:BIOMED CENTRAL LTD

    ISSN:1473-9542

    eISSN:1479-7364

  9. 他分野の基礎研究から学ぶ最先端研究 メタボローム解析を応用した個別化医療

    三枝 大輔, 佐藤 孝太, 齋藤 律水, 元池 育子, 中澤 徹, 山本 雅之

    日本眼科学会雑誌 122 (臨増) 30-30 2018年3月

    出版者・発行元:(公財)日本眼科学会

    ISSN:0029-0203

  10. 活動状態依存性に変化するHRVダイナミクスと主観的睡眠評価

    天野 領太, 辛島 彰洋, 元池 育子, 片山 統裕, 木下 賢吾, 中尾 光之

    生体医工学 Annual56 (Abstract) S331-S331 2018年

    出版者・発行元:公益社団法人 日本生体医工学会

    DOI: 10.11239/jsmbe.annual56.s331  

    ISSN:1347-443X

    eISSN:1881-4379

    詳細を見る 詳細を閉じる

    活動度や心拍変動(HRV)を長期計測し、そのダイナミクスを用いて被験者の生理機能や病態を特徴づけようとする研究は数多くある。しかし、HRVダイナミクスは姿勢や睡眠覚醒などの生理状態によって変化することから、機能的な特徴づけは簡単ではない。本研究では、22名の被験者(男14名、女8名、年齢分布23±3才)について、3軸加速度から状態カテゴリ(歩行、座位/立位、臥位)を推定すると共に、HRVを同時計測し、その状態依存性ダイナミクスを求めた。さらに、被験者の生理機能を総合的に特徴づけるために、最も深い睡眠である徐波睡眠を基底状態と考え、その時のダイナミクスを基準として状態依存性HRVダイナミクスを相対化した。また、主観的な睡眠評価と対応付けて解析を行った。その結果、主観的な睡眠評価によって3状態のHRVダイナミクスの関係性に違いがみられた。今後、睡眠の質と心臓血管制御系ダイナミクスについてさらに詳細に調べていきたい。

  11. 視神経挫滅モデル網膜のメタボローム解析

    佐藤孝太, 三枝大輔, 元池育子, 齋藤律水, 藤岡周, 山本雅之, 中澤徹

    日本緑内障学会抄録集 29th 2018年

  12. ゲノム情報と連携した日本人多層オミックス参照パネルの意義

    小柴生造, 小柴生造, 元池育子, 元池育子, 三枝大輔, 三枝大輔, 井上仁, 井上仁, 城田松之, 城田松之, 青木裕一, 青木裕一, 田高周, 田高周, 斎藤智, 木下賢吾, 木下賢吾, 山本雅之, 山本雅之

    糖尿病(Web) 61 (Suppl) 2018年

    ISSN:1881-588X

  13. 質量分析計を用いる大規模メタボローム解析におけるデータ補正について

    三枝大輔, 三枝大輔, 三枝大輔, 元池育子, 元池育子, 小柴生造, 小柴生造

    質量分析総合討論会講演要旨集 65th 2017年

  14. メタボロミクス解析を用いたサルコイドーシスの活動性予測バイオマーカーの検索

    蒲生俊一, 玉田勉, 村上康司, 三枝大輔, 元池育子, 有竹秀美, 奈良正之, 村松聡士, 村松聡士, 杉浦久敏, 一ノ瀬正和

    日本サルコイドーシス/肉芽腫性疾患学会雑誌 37 2017年

    ISSN:1883-1273

  15. マルチオミクスが解き明かす疾患生物学 日本人多層オミックス参照パネルの拡張

    小柴 生造, 三枝 大輔, 元池 育子, 小島 要, 城田 松之, 齋藤 智, 勝岡 史城, 河合 洋介, 山口 由美, 田邉 修, 長崎 正郎, 安田 純, 木下 賢吾, 山本 雅之

    日本生化学会大会プログラム・講演要旨集 89回 [1S05-5] 2016年9月

    出版者・発行元:(公社)日本生化学会

  16. 東北メディカル・メガバンク機構における血漿プロテオミクス解析

    城田 松之, 加藤 恭丈, 元池 育子, 木下 賢吾, 小柴 生造

    日本プロテオーム学会大会要旨集 2016 98-98 2016年

    出版者・発行元:日本プロテオーム学会(日本ヒトプロテオーム機構)

    DOI: 10.14889/jhupo.2016.0.98.0  

  17. 大規模コホートにおけるトランスオミクス解析

    三枝大輔, 三枝大輔, 三枝大輔, 元池育子, 元池育子, 小柴生造, 小柴生造

    日本プロテオーム学会大会プログラム・抄録集 2016 2016年

  18. 日本人多層オミックス参照パネルの公開

    小柴生造, 加藤恭丈, 三枝大輔, 元池育子, 城田松之, 斎藤智, 田邉修, 安田純, 木下賢吾, 山本雅之

    日本生化学会大会(Web) 88th 4T21L-07(3P0816) (WEB ONLY)-07(3P0816)] 2015年12月

    出版者・発行元:(公社)日本生化学会

  19. LC‐MSによる大規模コホートメタボローム解析

    三枝大輔, 加藤恭丈, 小柴生造, 元池育子, 荻島創一, 本橋ほづみ, 菅原準一, 中谷純, 寳澤篤, 峯岸直子, 木下賢吾, 田邉修, 山本雅之

    日本農芸化学会大会講演要旨集(Web) 2015 4SY19-2 (WEB ONLY) 2015年3月5日

    ISSN:2186-7976

  20. 血漿プロテオームによる大規模住民コホート研究

    加藤 恭丈, 小柴 生造, 五十嵐 和彦, 山本 雅之, 田邉 修, 蝦名 真行, 城田 松之, 元池 育子, 木下 賢吾, 工藤 久智, 信國 宇洋, 峯岸 直子, 三枝 大輔

    日本プロテオーム学会大会要旨集 2015 (0) 62-62 2015年

    出版者・発行元:日本プロテオーム学会(日本ヒトプロテオーム機構)

    DOI: 10.14889/jhupo.2015.0.62.0  

  21. Erratum: Global genetic response in a cancer cell: Self-organized coherent expression dynamics (PLoS ONE (2014) 9, 5, (e97411) DOI:10.1371/journal.pone. 0097411) 査読有り

    M. Tsuchiya, M. Hashimoto, Y. Takenaka, I. N. Motoike, K. Yoshikawa

    PLoS ONE 9 (8) 2014年8月8日

    出版者・発行元:PUBLIC LIBRARY SCIENCE

    DOI: 10.1371/journal.pone.0105491  

    ISSN:1932-6203

    eISSN:1932-6203

  22. Global Genetic Response in a Cancer Cell: Self-Organized Coherent Expression Dynamics (vol 9, e97411, 2014)

    M. Tsuchiya, M. Hashimoto, Y. Takenaka, I. N. Motoike, K. Yoshikawa

    PLOS ONE 9 (8) 2014年8月

    出版者・発行元:PUBLIC LIBRARY SCIENCE

    DOI: 10.1371/journal.pone.0105491  

    ISSN:1932-6203

  23. 眼疾患と遺伝子 緑内障のゲノム解析 次世代医療・個別化医療に向けて

    布施 昇男, 清水 愛, 木村 雅恵, 高野 良真, 石 棟, 宮澤 晃子, 国松 志保, 劉 孟林, 渡邉 亮, 安田 正幸, 横山 悠, 檜森 紀子, 津田 聡, 山本 耕太郎, 中澤 徹, 安田 純, 勝岡 史城, 小島 要, 成相 直樹, 松本 光代, 元池 育子, 長崎 正朗, 木下 賢吾, 五十嵐 和彦, 山本 雅之, 新堀 哲也, 青木 洋子, 松原 洋一, 舟山 亮, 長嶋 剛史, 中山 啓子, 眞島 行彦, 船山 智代, 田中 光一, 原田 高幸, 阿部 春樹, 福地 健郎, 安田 典子, 出田 秀尚, 鄭 暁東, 白石 敦, 大橋 裕一, 石田 誠夫, 原 岳, 金森 章泰, 山田 裕子, 中村 誠, 酒井 寛, Richards Julia E

    日本眼科学会雑誌 118 (3) 216-240 2014年3月

    出版者・発行元:(公財)日本眼科学会

    ISSN:0029-0203

    詳細を見る 詳細を閉じる

    主に1990年代から始まった遺伝要因が発症に関係する疾患の解析は,単一遺伝子疾患や遺伝子変異(mutation)から多因子疾患の感受性因子である遺伝子多型(variation)へと移行してきた.個人ゲノムの解析が進むにつれて,個々人の間にはゲノム全体で数百万ヶ所の塩基配列が異なることが判明している.この塩基配列の相違が頻度の高い疾患(common disease)の発症に関わっていることが証明されてきた.近年ゲノム全体にわたる一塩基多型(single nucleotide polymorphism:SNP)を用いた相関解析(genome-wide association study:GWAS)が盛んに行われてきているが,高頻度の多型(common variant)はその病気への寄与が比較的小さいことから,臨床研究をより精度の高いものにするためには,common variantに加えて,病気への寄与度が大きい低頻度の多型(rare variant)の解析も行うことが必要である.さらにゲノム情報を用いた次世代医療,個別化医療に向け,種々の表現型(endophenotype)との関連を調べることは重要である.本研究において,我々は緑内障の病態解明をゲノム解析の観点から検討した.現在まで緑内障原因遺伝子は数種類同定されているが,当初はメンデル遺伝性の家系解析からの同定が主であった.2007年,GWASによって,LOXL1遺伝子の多型と【嚢】性緑内障が関連すると報告され,我々を含む多施設で追試された.それ以降,SNPを用いた相関解析が主流となってきており,原発開放隅角緑内障(primary open-angle glaucoma:POAG),正常眼圧緑内障(normal-tension glaucoma:NTG)に関連した遺伝子としてCDKN2B-AS1遺伝子などが発表された.また我々は,緑内障GLC1B遺伝子座が存在する常染色体2番上において,SNPを用いた相関解析により,Hexokinase 2(HK2)遺伝子多型rs678350がPOAG,NTGに関連していることを明らかにし,NCK2遺伝子多型rs2033008がNTGに関連していることを示した.マウスを用いてHk2,Nck2蛋白質の免疫組織染色を行った結果,神経節細胞に発現がみられ,緑内障の病態に関連していると考えられた.近年,遺伝子解析は,マーカーを用いた相関解析から次世代シークエンサーを用いた網羅的な解析へと移行してきている.その中でも,全エクソン解析(エクソーム解析)は,約20万個のエクソンをすべて解析するものである.これを発達緑内障早発型の解析に用いた.発達緑内障早発型では,CYP1B1遺伝子が唯一発見されている原因遺伝子であるが,新規原因遺伝子解析のために,今回次世代シークエンサーでの解析に適する症例・家系の収集を行い,エクソーム解析を行った.CYP1B1遺伝子スクリーニングの後,CYP1B1遺伝子変異陰性の症例を用い,エクソーム解析を行った.その結果,発達緑内障早発型では原因遺伝子について遺伝的異質性が高いこと,de novo変異も原因の候補であることを明らかにした.次に,POAGおよびNTGにおける新規原因遺伝子解明のため,POAG1家系,NTG2家系のエクソーム解析を行った.1000 Genomes,SNPデータベースでフィルターをかけ,各々数十個〜100個候補遺伝子を抽出した.今回の3家系に共通している候補遺伝子はなく,2家系においては神経系の細胞の分化に関連する転写因子とアクチン関連分子が候補遺伝子であった.また,一般の孤発例にも適用を開始し,この手法は緑内障原因遺伝子の探索に有用と考えられた.ゲノム情報を活用しゲノム医療を現実にするためには,遺伝子,環境,病気の3つの因果関係を明らかにしていかなければならない.今回,東北大学東北メディカル・メガバンクにおいて大規模バイオバンクを構築し,集積される生体試料から疾患と関連する遺伝子の同定と,それらのバイオマーカーの探索を開始した.2013年度中に1,000人(深度30倍以上)の全ゲノム配列解析を実施し,日本人ゲノムのSNPを頻度0.5%以下まで決定して日本人標準ゲノムリファレンスパネルを作成し,疾患感受性と関連する遺伝子を同定する.解析により同定した多型の中から日本人特有のもの,関連遺伝子を抽出し,日本人に最適化した緑内障SNPアレイを開発する.ゲノム情報と健康情報・診療情報とを集約することで,緑内障の予防や診断精度の向上,治療効果の向上のための緑内障個別化医療の実現を目指すことが可能になると期待される.(著者抄録)

  24. 24pPSB-13 信号伝播履歴に依存して変形する経路における経路間相互作用(24pPSB 領域11ポスターセッション,領域11(統計力学,物性基礎論,応用数学,力学,流体物理))

    元池 N. 育子, 今村(滝川) 寿子

    日本物理学会講演概要集 65 (2) 260-260 2010年8月18日

    出版者・発行元:一般社団法人日本物理学会

    ISSN:1342-8349

  25. 樹状形状に依存した演算機能の解析

    今村(滝川)寿子, 元池N.育子, 元池N.育子

    日本数理生物学会大会講演要旨集 20th 2010年

  26. 場の幾何学的形状に依存する興奮波伝播パターンと信号処理

    元池N. 育子

    システム/制御/情報 54 (1) 3-8 2010年

    出版者・発行元:一般社団法人 システム制御情報学会

    DOI: 10.11509/isciesci.54.1_3  

    ISSN:0916-1600

    eISSN:2424-1806

  27. 29pPSB-31 非線形アナログ回路と連続抵抗体のネットワークにおけるパターン形成 : 実デバイスによるDoE拡散実験(29pPSB 領域11ポスターセッション,領域11(統計力学,物性基礎論,応用数学,力学,流体物理))

    鈴木 洋平, 元池 N.育子, 浅井 哲也

    日本物理学会講演概要集 61 (1) 316-316 2006年3月4日

    出版者・発行元:一般社団法人日本物理学会

    ISSN:1342-8349

  28. 22aPS-13 アナログLSI上に実装した拡散Lotka-Volterra系における空間パターンの発生(領域11ポスターセッション,領域11(統計力学,物性基礎論,応用数学,力学,流体物理))

    神谷 泰史, 元池 N.育子, 浅井 哲也

    日本物理学会講演概要集 60 (2) 204-204 2005年8月19日

    出版者・発行元:一般社団法人日本物理学会

    ISSN:1342-8349

  29. 22aPS-14 二層連続抵抗体における空間パターンの発生メカニズム(領域11ポスターセッション,領域11(統計力学,物性基礎論,応用数学,力学,流体物理))

    鈴木 洋平, 元池 N.育子, 浅井 哲也

    日本物理学会講演概要集 60 (2) 204-204 2005年8月19日

    出版者・発行元:一般社団法人日本物理学会

    ISSN:1342-8349

  30. Turing パターンを発生するシンプルな反応拡散セルオートマトンモデルとその集積回路化 : 縞・斑点画像復元の応用に向けて

    鈴木 洋平, 高山 貴裕, 元池 N. 育子, 浅井 哲也

    電子情報通信学会技術研究報告. NLP, 非線形問題 104 (753) 29-34 2005年3月18日

    出版者・発行元:一般社団法人電子情報通信学会

    ISSN:0913-5685

    詳細を見る 詳細を閉じる

    本研究は、欠損や汚れのある画像パターンをリアルタイムに修復するLSIの開発を目指したものである。そのために、生物の形づくりの原理に基づいて、指紋や体模様に見られる縞・斑点などのTuringパターンを生成・修復する反応拡散モデルを提案する。その後、そのモデルを実装する反応拡散チップの並列アーキテクチャを提案する。回路シミュレーションにより、このLSIが縞(斑点)パターンを復元できることを示す。

  31. 巨大リポソームネットワークの自発的形成

    野村 M.慎一郎, 元池 N.育子, 秋吉 一成

    生物物理 43 (0) S110 2003年

    出版者・発行元:一般社団法人 日本生物物理学会

    DOI: 10.2142/biophys.43.S110_3  

    ISSN:0582-4052

  32. 形に依存するシンプルな情報処理機能

    元池育子

    生物物理 43 (2) 81-86 2003年

    出版者・発行元:一般社団法人日本生物物理学会

    DOI: 10.2142/biophys.43.81  

    ISSN:0582-4052 1347-4219

    eISSN:1347-4219

    詳細を見る 詳細を閉じる

    In living organisms, signals propagate through various kinds of geometrical or boundary paths. It is well established that a traveling wave can be generated on an excitable field; this generation is described by reaction-diffusion equations for an activator and inhibitor. I use a numerical simulation to show that the signaling pulse can be transmitted from an excitable field to an opposing excitable field via an intervening passive diffusion field in a characteristic manner that depends upon the spatial geometry of the excitable fields. Using such characteristics, it is possible to design various kinds of simple information operations.

  33. 場の幾何学的形状に依存する興奮波伝播パターンと情報処理

    元池育子

    数理解析研究所講究録 1313 47-52 2003年

    出版者・発行元:京都大学数理解析研究所

    ISSN:1880-2818

  34. 反応拡散場の非対称結合系での情報処理演算の試み (反応拡散系 : 生物・化学における現象とモデル)

    元池, N.育子

    数理解析研究所講究録 1167 25-26 2000年8月

    出版者・発行元:京都大学数理解析研究所

    ISSN:1880-2818

  35. 対称性の破れが創りだす美

    元池育子

    化学 4 1999年

  36. 興奮場の時空特性を活用した時空間上の情報処理

    吉川 研一, 元池 育子

    電子情報通信学会ソサイエティ大会講演論文集 1998 (2) 182-183 1998年9月7日

    出版者・発行元:一般社団法人電子情報通信学会

  37. 25a-H-1 興奮場(反応拡散場)を用いた情報処理

    元池 育子, 吉川 研一

    日本物理学会講演概要集 53 (2) 734-734 1998年9月5日

    出版者・発行元:一般社団法人日本物理学会

    ISSN:1342-8349

  38. 興奮場の特質を用いた情報処理演算(基研研究会「ニューラルネットワーク~これからの統計力学的アプローチ~」,研究会報告)

    元池, 育子

    物性研究 70 (3) 413-415 1998年6月20日

    出版者・発行元:物性研究刊行会

    ISSN:0525-2997

    詳細を見る 詳細を閉じる

    この論文は国立情報学研究所の電子図書館事業により電子化されました。

  39. 30p-YJ-3 興奮場の特質を活用したロジック演算の試み

    元池 育子, 吉川 研一

    日本物理学会講演概要集 53 (1) 643-643 1998年3月10日

    出版者・発行元:一般社団法人日本物理学会

    ISSN:1342-8349

  40. 6a-YD-9 興奮場と拡散場を配置した空間上での演算の試み

    元池 育子, 吉川 研一

    日本物理学会講演概要集 52 (2) 745-745 1997年9月16日

    出版者・発行元:一般社団法人日本物理学会

    ISSN:1342-8349

  41. 31a-PS-42 興奮場での演算の試み

    元池 育子, 吉川 研一

    日本物理学会講演概要集 52 (1) 741-741 1997年3月17日

    出版者・発行元:一般社団法人日本物理学会

    ISSN:1342-8349

︎全件表示 ︎最初の5件までを表示

書籍等出版物 2

  1. ニューロンのダイナミクスと情報処理

    脳のフィジックス (長谷川建治・吉岡亨編, 共立出版) 2004年

  2. Simple Signal Processing Depends on the Geometry of the Medium

    Chemical Analysis Based on Nonlinearity (ed. by Satoshi Nakata, Nova Science Pub Inc Published) 2003年

講演・口頭発表等 9

  1. 日本人集団における食習慣と血漿中脂質濃度の関連解析

    佐藤 允治, 菱沼 英史, 三枝 大輔, 元池 育子, 木下 賢吾, 小柴 生造

    脂質生化学研究 2023年5月

  2. 血清メタボロームと認知機能変化の関連 NILS-LSAの観察結果から

    寳澤 篤, 大塚 礼, 張 シュ, 菱沼 英史, 元池 育子, 三枝 大輔, 中谷 直樹, 小柴 生造, 荒井 秀典

    Journal of Epidemiology 2023年2月

  3. 遺伝・生活習慣が日本人の血中代謝プロファイルに与える影響の解析

    小柴 生造, 元池 育子, 井上 仁, 菱沼 英史, 青木 裕一, 櫻井 美由紀, 佐藤 允治, 七谷 圭, 田高 周, 城田 松之, 木下 賢吾, 山本 雅之

    日本生化学会大会プログラム・講演要旨集 2022年11月

  4. jMorp: Japanese Multi Omics Reference Panel

    田高 周, 菱沼 英史, 井上 仁, 青木 裕一, 岡村 容伸, 川嶋 順子, 大槻 晃史, 田口 恵子, 菅野 貴成, 元池 育子, 勝岡 史城, 小柴 生造, 木下 賢吾

    トーゴーの日2022 2022年10月5日

  5. 代謝プロファイルに影響を与える遺伝要因の網羅的解析

    小柴 生造, 元池 育子, 三枝 大輔, 井上 仁, 菱沼 英史, 青木 裕一, 田高 周, 城田 松之, 木下 賢吾, 山本 雅之

    日本生化学会大会プログラム・講演要旨集 2021年11月

  6. 血漿メタボロームと頸動脈内膜中膜肥厚の関連

    寳澤 篤, 小柴 生造, 平田 匠, 中村 智洋, 土屋 菜歩, 成田 暁, 小暮 真奈, 元池 育子, 三枝 大輔, 峯岸 直子, 栗山 進一, 田宮 元, 辻 一郎, 木下 賢吾, 呉 繁夫

    日本高血圧学会総会プログラム・抄録集 2019年10月

  7. コホート調査における代謝プロファイルの経時変化の解析

    小柴 生造, 元池 育子, 三枝 大輔, 井上 仁, 菱沼 英史, 青木 裕一, 田 高周, 城田 松之, 木下 賢吾, 山本 雅之

    日本生化学会大会プログラム・講演要旨集 2019年9月

  8. メタボロームGWASによる日本人の代謝プロファイルの解析

    小柴 生造, 元池 育子, 三枝 大輔, 井上 仁, 青木 裕一, 田高 周, 城田 松之, 木下 賢吾, 山本 雅之

    日本生化学会大会プログラム・講演要旨集 2018年9月

  9. 高精度日本人多層オミックス参照パネルの提供

    小柴 生造, 元池 育子, 三枝 大輔, 井上 仁, 城田 松之, 斎藤 智, 木下 賢吾, 山本 雅之

    生命科学系学会合同年次大会 2017年12月

︎全件表示 ︎最初の5件までを表示

共同研究・競争的資金等の研究課題 14

  1. 尿毒素による細胞内代謝失調を標的とした高齢者の慢性腎臓病合併症の治療開発

    佐藤 恵美子, 田中 哲洋, 宮崎 真理子, 元池 育子, 山越 聖子, 三枝 大輔, 吉田 舞

    2023年4月1日 ~ 2027年3月31日

  2. 紫外線感受性核酸多型に基づく尋常性白斑発症予測プログラムの構築

    山崎 研志, 小島 要, 元池 育子

    2022年4月1日 ~ 2025年3月31日

  3. 配偶子のゲノムモダリティと疾患

    岡田 由紀, 元池 育子

    提供機関:Japan Society for the Promotion of Science

    制度名:Grants-in-Aid for Scientific Research Grant-in-Aid for Transformative Research Areas (A)

    研究種目:Grant-in-Aid for Transformative Research Areas (A)

    研究機関:The University of Tokyo

    2020年11月19日 ~ 2025年3月31日

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    本研究課題では、精製タンパク質や生化学的に抽出した精子クロマチンを用いて、以下の3つの目標を設定している。(目標1)DNA物性の観点から、精子クロマチンの局所構造を明らかにする; (目標2)精子核内染色体配置を明らかにし、種間比較によりその生物学意義を探る; (目標3)プロタミン凝集異常を定量化し、男性不妊症の理解に繋げる。当該年度の実績を如何に記載する。 目標1:精子クロマチンの試験管内再構成と、ex vivo再構成を計画している。前者は使用予定の機器がCovid-19の影響で設置されておらず、進捗はない。後者は再構成の条件検討を行い、プロトコルの確立に至った。さらに二価イオンが精子クロマチン構造に影響することを明らかにした。 目標2:マウス・ヒト・ブタで実験を進めている。マウスはATAC-seqによる解析が完了し、精子形成過程におけるクロマチン凝縮のタイミングと程度を定量的に示すことができた。 目標3:ヒト不妊患者精子のシーケンス解析を行い、不妊患者に特徴的なクロマチン凝縮異常パターンを見出すことができた。

  4. イメージングMSによる生体内スフィンゴ脂質の組織分布立体的可視化手法の開発

    三枝 大輔, 可野 邦行, 元池 育子

    提供機関:Japan Society for the Promotion of Science

    制度名:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    研究種目:Grant-in-Aid for Scientific Research (C)

    研究機関:Tohoku University

    2017年4月1日 ~ 2020年3月31日

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    平成30年度は、初めに前年度までに確立した川本フィルムによる連続切片作成技術の評価を実施し、マウスあるいはゼブラフィッシュ等の硬組織および軟組織を同時に含む複数種の連続切片の作成に成功した。また、得られた組織切片を高分解能型の質量分析イメージング(MSI)を用いて分析したところ、一部のリゾリン脂質の分布局在を得ることにも成功したことから、川本フィルムによるMSI用組織切片作成技術が、本研究の目的達成に極めて重要であることが明らかになった。現在原著論文として投稿中であり、近日中に学会発表を通じて公開する予定である。 次に、連続切片におけるMSIデータの三次元可視化法の開発にも着手し、現在までに複数枚のMSI画像データをソフトウェアを用いて統合できる可能性を見出している。 さらに、本研究において新たに開発したDESI-DIUTHAMEを組み合わせた手法(浜松ホトニクスとの共同研究・特許出願中)により、m/z 500以下の領域で検出される分子群の検出感度向上に加え、セラミド等のスフィンゴ脂質の検出には成功し、さらにS1Pの検出にも可能性を見出している。今後、本研究課題であるS1Pの機能解析を目的としたMSI検出法の開発に向けて、さらに選択的な抽出溶媒による検出条件を最適化する予定である。 また、平成30年度後半には、川本フィルムを用いることで、9日齢のマウスから全身組織切片の作成に成功している(投稿論文中に記載)。従って、平成31年度は上記全ての手法を用いることで、マウス全身に含まれるスフィンゴ脂質の分布の立体可視化に挑戦する予定である。

  5. 生命現象の階層ダイナミクスの実空間モデリング

    吉川 研一, 湊元 幹太, 元池 育子, 市川 正敏

    提供機関:Japan Society for the Promotion of Science

    制度名:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

    研究種目:Grant-in-Aid for Scientific Research (A)

    研究機関:Doshisha University

    2011年4月1日 ~ 2016年3月31日

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    ゲノムDNA、細胞、細胞集団の、各階層での生命現象の特質を明らかにするため、実空間上のモデル系を構築することが中心的な研究課題。当初の予想を上回る成果が得られてきている。1)遺伝子活性のスイッチングについては、光感受性の界面活性剤により、DNAの高次構造転移を引き起すことにより、複数の遺伝子のスイチングを起こすことに成功している。 2)細胞サイズ小胞の形成手法の確立および、細胞サイズ空間での生化学反応(遺伝子発現など)の特異性の実証など、この課題は大きく進展した。3)網羅的なヒト遺伝子の発現解析により遺伝子群が特異的な大域的ドメインを形成していることを明らかにし、理論モデルを構築した。

  6. 複雑なネットワーク様信号伝播経路における経路刈り込みによる信号処理機能の顕在化

    元池 育子

    提供機関:Japan Society for the Promotion of Science

    制度名:Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    研究種目:Grant-in-Aid for Challenging Exploratory Research

    研究機関:Tohoku University

    2011年 ~ 2013年

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    反応拡散系を基盤とした離散ダイナミクスモデルを用いて、樹状経路が信号伝播履歴に応じて伸展・縮退系に対して、特に縮退に焦点をあて、経路・伝播パターンの変化を調べ、また同系の3次元への拡張系に成功した。 信号伝播履歴に応じて径が動的に変化するダイナミクスの実現には、経路の初期状態をランダムネットワークとする減算型樹状変化系が適していること、また神経細胞の初期形成過程に見られるような動的な経路変化を表現するには、経路のvolumeに相当するような特徴量の規定が重要であることを見いだした。

  7. 曲率効果に起因する心筋細胞でのラセン波形成機構

    アグラゼ コンスタンチン, 馬籠 信之, 元池 育子, 今村 寿子

    提供機関:Japan Society for the Promotion of Science

    制度名:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    研究種目:Grant-in-Aid for Scientific Research (B)

    研究機関:Kyoto University

    2009年 ~ 2012年

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    培養した心筋細胞を用い、特に障害領域を興奮波が通過する際の挙動について、実験ならびに理論の面から検討した。伝播の様式は細胞の興奮性に大きく依存し、興奮波の不安定化による自発的な端点形成も確認された。また、光感受性物質を混在させておくことによって外部からの光照射によって細胞活動を可逆的に制御したり、微細繊維を用いることで配向性の高い細胞培養手法を確立したりすることを可能とした。

  8. ゆらぎを積極的に利用するナノ情報処理システムの開拓

    浅井 哲也, 大矢 剛嗣, 元池 育子

    提供機関:Japan Society for the Promotion of Science

    制度名:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

    研究種目:Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

    研究機関:Hokkaido University

    2008年 ~ 2012年

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    ナノ集積デバイスにおけるゆらぎの存在を前提として、ゆらぎを利用して基本的な情報処理を行う以下のシステム設計を行った:(i) 確率共鳴による微弱信号検出器,(ii) ゆらぎを利用するA/D 変換器(雑音の力を借りて低周波雑音を抑制), (iii) 高速信号伝送路(雑音の力を借りて超低消費電力回路で高速パルス伝送), (iv) 雑音誘起同期回路(雑音の力を借りて独立した回路群の位相を強制同期), (v) 確率共鳴メモリ(雑音の力を借りて極低電圧・低消費電力メモリを正しく動作させる)。これらのうち、(i), (iii), (v)について、A04 班とともに分子ナノデバイス設計を行い、(i), (iii)についてはデバイス試作と所望の動作確認ができた。残る(ii), (iv), (v)については、半導体ナノ集積でバイス上にて評価を行い、想定通りの動作を得ることができた。

  9. 時間発展する樹状経路構造上の信号伝播様式

    元池 育子

    2007年 ~ 2011年

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    信号処理素子である神経細胞や、粘菌の管などは、枝分かれした樹状という特徴的な「形」をしています。そしてこの形は、信号の伝播に応じて、少しずつ変わっていきます。この「形」をとることによるメリットは何なのか、単純化した数理モデルを用いて、樹状を走る信号のパターンから機能を読み取り、明らかにしていきます。発展として、樹状の結合系についても検証し、形と機能の関係から、生命の信号処理の基盤にアプローチします。

  10. 時間発展するパターンを信号伝播媒体とする反応拡散信号伝播様式

    元池 育子

    提供機関:Japan Society for the Promotion of Science

    制度名:Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    研究種目:Grant-in-Aid for Young Scientists (B)

    研究機関:Kyoto University

    2008年 ~ 2010年

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    時間発展するパターンについて、信号伝播離散ダイナミクスと相互作用を行うスポットの分裂パターン形成の離散モデルを提案し、パターンの時間変化のパラメータ依存性から、スポット状の場が等方的に進展する条件等を見いだした。また場の形状等に依存して、信号の単方向伝播・消失・フィルタリング・回転波の発生等が起こることを見いだし、これらの信号伝播様式を通して、信号の融合および、時間差を因子とした論理積演算が行われうることを示した。

  11. 興奮特性をもつ信号媒体の分岐/樹状空間構造を活用した信号処理機能

    元池 育子

    提供機関:Japan Society for the Promotion of Science

    制度名:Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    研究種目:Grant-in-Aid for Young Scientists (B)

    研究機関:Future University-Hakodate

    2004年 ~ 2005年

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    本研究は、細胞内経路における信号の符号化の由来として、神経細胞一般にみられる2つの特性、信号発生・伝播の「興奮特性」と、複雑な信号伝播経路形状「分岐/樹状構造」に着目し、興奮特性をもつ場(信号伝播媒体)が分岐・樹状構造をとることによってどのような信号処理機能が得られ得るのかの解明の端につくことを目的としている。 上記の目的のため、前年度は樹状形状形成のシンプルなダイナミクス提案とその形状特性の同定、及び信号伝播特性の多様性について見出した。本年度は、よりシンプルな樹状形成のダイナミクス同定と、信号伝播と経路形成の2種のダイナミクスが相互作用を行う系での形成形状と信号伝播パターンの変化について、フラクタル次元やパターン成長速度等の解析を行い、生成規則パラメータの形成パターンに及ぼす影響、樹状枝密度の違いなどを明らかにした。 結果として、信号伝播が経路形成に正の影響を及ぼす場合には、及ぼさない場合に比べ、形成された経路形状の樹状枝の密度、曲がりくねり具合など、形状の定量的な変化は見られたが、大きな定性的な変化は見られなかった。また信号伝播が経路形成に正負両方の影響を及ぼす場合には、経路形状特性による螺旋波の発生の有無、信号の伝播パターンによって、パラメータによってはダイナミックな経路形状の変化が見られた。これらは、樹状経路上で見られる、情報処理機構の基盤となる単方向信号伝播(ダイオード特性)やペースメーカーの役割も果たす螺旋波発生機構と合わせ、信号伝播パターンの多様性による信号伝播経路形状に対する学習に似た効果を示唆していると考えられる。

  12. 興奮場の結合の非対称性を活用した並列・時間情報演算に関する研究

    元池 育子

    提供機関:Japan Society for the Promotion of Science

    制度名:Grants-in-Aid for Scientific Research Grant-in-Aid for JSPS Fellows

    研究種目:Grant-in-Aid for JSPS Fellows

    研究機関:Kyoto University

    2000年 ~ 2001年

  13. 信号伝播媒体の形状特性を用いた信号処理モデル 競争的資金

  14. signal processing by utilizing geometrical features of signal propagation media 競争的資金

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