研究者詳細

顔写真

アオキ　ユウイチ
青木　裕一
Yuichi Aoki
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
講師
学位

  • 博士（工学） （東北大学）

研究キーワード 1

  • 生命情報システム科学

研究分野 1

  • ライフサイエンス / システムゲノム科学 /

論文 37

  1. ibSLS: A Biobank for Democratizing Access to Multi-Omics Data and Biospecimens from Spaceflight Research

    Akihito Otsuki, Yuichi Aoki, Risa Okada, Daisuke Kamimura, Dai Shiba, Eiji Hishinuma, Seizo Koshiba, Fumiki Katsuoka, Kengo Kinoshita, Takafumi Suzuki, Akira Uruno, Masayuki Yamamoto

    2025年9月12日

    出版者・発行元： Cold Spring Harbor Laboratory

    DOI： 10.1101/2025.09.08.675003 　

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    Abstract During spaceflight, astronauts are exposed to extreme conditions such as microgravity, cosmic radiation, and confinement, which can cause a wide range of health problems. To elucidate the molecular mechanisms underlying these issues and to develop intervention strategies for maintaining physiological homeostasis during space missions, space life science research using mouse models is actively conducted on the International Space Station (ISS). However, because of the high cost and technical complexity of spaceflight experiments, it is critical to maximize the scientific value of each mission by ensuring broad accessibility to both data and biospecimens. To this end, we developed the integrated biobank for Space Life Sciences (ibSLS; https://ibsls.megabank.tohoku.ac.jp), a data-visualization and sample-sharing platform that provides access to transcriptomic and metabolomic datasets generated from JAXA’s Mouse Habitat Unit (MHU) missions. The platform features a user-friendly interface, tools for cross-mission analysis, and integration with human multi-omics databases, enabling cross-species comparisons. In addition, ibSLS facilitates biospecimen requests to support downstream research. By promoting open access to spaceflight-derived data and biological resources, ibSLS encourages the participation of researchers from diverse fields in space life science. We believe that ibSLS will make a valuable contribution to both biomedical research on spaceflight-related health issues and the study of diseases on Earth.

  2. Effect of Japanese Traditional Medication on Males with Diarrhea-predominant Irritable Bowel Syndrome and Gut Microbiome: A Single-arm Prospective Study

    Ryutaro Arita, Shin Takayama, Toru Tamahara, Yuichi Aoki, Soichiro Kaneko, Akiko Kikuchi, Junko Kawashima, Yoshiyuki Kasahara, Kota Ishizawa, Ritsuko Shimizu, Tadashi Ishii

    European Journal of Integrative Medicine　102512-102512　2025年6月

    出版者・発行元： Elsevier BV

    DOI： 10.1016/j.eujim.2025.102512 　

    ISSN：1876-3820

  3. Identifying critical age and gender-based metabolomic shifts in a Japanese population of the Tohoku Medical Megabank cohort. 国際誌

    Miyuki Sakurai, Ikuko N Motoike, Eiji Hishinuma, Yuichi Aoki, Shu Tadaka, Mana Kogure, Masatsugu Orui, Mami Ishikuro, Taku Obara, Naoki Nakaya, Kazuki Kumada, Atsushi Hozawa, Shinichi Kuriyama, Masayuki Yamamoto, Seizo Koshiba, Kengo Kinoshita

    Scientific reports　14　(1)　15681-15681　2024年7月8日

    DOI： 10.1038/s41598-024-66180-0 　

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    Understanding the physiological changes associated with aging and the associated disease risks is essential to establish biomarkers as indicators of biological aging. This study used the NMR-measured plasma metabolome to calculate age-specific metabolite indices. In doing so, the scope of the study was deliberately simplified to capture general trends and insights into age-related changes in metabolic patterns. In addition, changes in metabolite concentrations with age were examined in detail, with the period from 55-59 to 60-64 years being a period of significant metabolic change, particularly in men, and from 45-49 to 50-54 years in females. These results illustrate the different variations in metabolite concentrations by sex and provide new insights into the relationship between age and metabolic diseases.

  4. 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.

  5. Detection and Correction of Sample Misidentifications in a Biobank Using the MassARRAY System and Genomic Information. 国際誌

    Hisaaki Kudo, Noriko Ishida, Takahiro Nobukuni, Yuichi Aoki, Sakae Saito, Ichiko Nishijima, Takahiro Terakawa, Masayuki Yamamoto, Naoko Minegishi, Riu Yamashita, Kazuki Kumada

    Biopreservation and biobanking　2023年12月11日

    DOI： 10.1089/bio.2022.0211 　

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    With the number of samples increasing in many biobanks, one of the most pressing tasks is recording the correct relationships between information and the specimens. Genomic information is useful in determining the identity of these specimens. The Tohoku Medical Megabank Organization is running one of the largest biobanks in Japan. Here, we introduce a management system, which includes the development of a new probe set for the MassARRAY system for use during the production of proliferating T cells (T cells) and lymphoblastoid cell lines (LCLs). We selected single nucleotide variants that could be detected by next-generation sequencing and showed high resolution with ∼0.5 minor allele frequencies. After checking the set of probes against 96 samples from 48 people, we obtained no contradictory results in comparison with our genome sequence information. When we applied the set to our 3035 LCLs and 2256 T cells, the result showed 98.93% consistency with the corresponding genomic information. We surveyed the handling records of the 1.07% of samples that showed inconsistencies, and found that most had resulted from human errors (ID swapping between samples) during manual operations. After improving a few error-prone protocols, the error rate dropped to 0.47% for LCLs and 0% for T cells. Overall, the system that we developed shows high accuracy with easy and fast operability, and provides a good opportunity to improve the validation procedure to facilitate high-quality banking, especially in cases involving genomic information.

  6. Effects of NRF2 polymorphisms on safety and efficacy of bardoxolone methyl: subanalysis of TSUBAKI study 査読有り

    Kazuaki Ikejiri, Takafumi Suzuki, Satsuki Muto, Hirotaka Takama, Kengo Yamawaki, Tatsuya Miyazawa, Itaru Urakawa, Yuichi Aoki, Akihito Otsuki, Fumiki Katsuoka, Kengo Kinoshita, Masaomi Nangaku, Tadao Akizawa, Masayuki Yamamoto

    Clinical and Experimental Nephrology　2023年11月14日

    DOI： 10.1007/s10157-023-02427-w 　

  7. jMorp: Japanese Multi-Omics Reference Panel update report 2023. 国際誌

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

    Nucleic acids research　2023年11月1日

    DOI： 10.1093/nar/gkad978 　

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    Modern medicine is increasingly focused on personalized medicine, and multi-omics data is crucial in understanding biological phenomena and disease mechanisms. Each ethnic group has its unique genetic background with specific genomic variations influencing disease risk and drug response. Therefore, multi-omics data from specific ethnic populations are essential for the effective implementation of personalized medicine. Various prospective cohort studies, such as the UK Biobank, All of Us and Lifelines, have been conducted worldwide. The Tohoku Medical Megabank project was initiated after the Great East Japan Earthquake in 2011. It collects biological specimens and conducts genome and omics analyses to build a basis for personalized medicine. Summary statistical data from these analyses are available in the jMorp web database (https://jmorp.megabank.tohoku.ac.jp), which provides a multidimensional approach to the diversity of the Japanese population. jMorp was launched in 2015 as a public database for plasma metabolome and proteome analyses and has been continuously updated. The current update will significantly expand the scale of the data (metabolome, genome, transcriptome, and metagenome). In addition, the user interface and backend server implementations were rewritten to improve the connectivity between the items stored in jMorp. This paper provides an overview of the new version of the jMorp.

  8. 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　95回　1T17e-02　2022年11月

    出版者・発行元： (公社)日本生化学会

  9. 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　1　2022年10月5日

    出版者・発行元： JST NBDC事業推進部

    DOI： 10.18908/togo2022.p040 　

  10. ATTED-II v11: A Plant Gene Coexpression Database Using a Sample Balancing Technique by Subagging of Principal Components.

    Takeshi Obayashi, Himiko Hibara, Yuki Kagaya, Yuichi Aoki, Kengo Kinoshita

    Plant & cell physiology　63　(6)　869-881　2022年6月15日

    DOI： 10.1093/pcp/pcac041 　

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    ATTED-II (https://atted.jp) is a gene coexpression database for nine plant species based on publicly available RNAseq and microarray data. One of the challenges in constructing condition-independent coexpression data based on publicly available gene expression data is managing the inherent sampling bias. Here, we report ATTED-II version 11, wherein we adopted a coexpression calculation methodology to balance the samples using principal component analysis and ensemble calculation. This approach has two advantages. First, omitting principal components with low contribution rates reduces the main contributors of noise. Second, balancing large differences in contribution rates enables considering various sample conditions entirely. In addition, based on RNAseq- and microarray-based coexpression data, we provide species-representative, integrated coexpression information to enhance the efficiency of interspecies comparison of the coexpression data. These coexpression data are provided as a standardized z-score to facilitate integrated analysis with different data sources. We believe that with these improvements, ATTED-II is more valuable and powerful for supporting interspecies comparative studies and integrated analyses using heterogeneous data.

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

    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)　44-44　2021年12月10日

    DOI： 10.1038/s41439-021-00175-5 　

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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.

  12. 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　94回　[P-837]　2021年11月

    出版者・発行元： (公社)日本生化学会

  13. Identification of the Genes Coding for Carthamin Synthase, Peroxidase Homologs that Catalyze the Final Enzymatic Step of Red Pigmentation in Safflower (Carthamus tinctorius L.).

    Toshiyuki Waki, Miho Terashita, Naoki Fujita, Keishi Fukuda, Mikiya Kato, Takashi Negishi, Hiromi Uchida, Yuichi Aoki, Seiji Takahashi, Toru Nakayama

    Plant & cell physiology　2021年8月3日

    DOI： 10.1093/pcp/pcab122 　

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    Carthamin, a dimeric quinochalcone that is sparingly soluble in water, is obtained from the yellow-orange corolla of fully blooming safflower (Carthamus tinctorius L.) florets. Carthamin is a natural red colorant, which has been used worldwide for more than 4500 years and is the major component of Japanese "beni" used for dyeing textiles, cosmetics, and as a food colorant. The biosynthetic pathway of carthamin has long remained uncertain. Previously, carthamin was proposed to be derived from precarthamin (PC), a water-soluble quinochalcone, via a single enzymatic process. In this study, we identified the genes coding for the enzyme responsible for formation of carthamin from PC, termed carthamin synthase (CarS), using enzyme purification and transcriptome analysis. The CarS proteins were purified from the cream-colored corolla of safflower and identified as peroxidase homologs (CtPOD1, CtPOD2, and CtPOD3). The purified enzyme catalyzed the oxidative decarboxylation of PC to produce carthamin using O2, instead of H2O2, as an electron acceptor. In addition, CarS catalyzed the decomposition of carthamin. However, this enzymatic decomposition of carthamin could be circumvented by adsorption of the pigment to cellulose. These CtPOD isozymes were not only expressed in the corolla of the carthamin-producing orange safflower cultivars, but were also abundantly expressed in tissues and organs that did not produce carthamin and PC. One CtPOD isozyme, CtPOD2, was localized in the extracellular space. Based on the results obtained, a model for the stable red pigmentation of safflower florets during flower senescence and the traditional "beni" manufacturing process is proposed.

  14. 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 　

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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.

  15. 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.

  16. 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.

  17. Identification of critical genetic variants associated with metabolic phenotypes of the Japanese population

    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)　2020年12月

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

    DOI： 10.1038/s42003-020-01383-5 　

    eISSN：2399-3642

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    <title>Abstract</title> 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.

  18. Landscape of electrophilic and inflammatory stress-mediated gene regulation in human lymphoblastoid cell lines

    Noriko Ishida, Yuichi Aoki, Fumiki Katsuoka, Ichiko Nishijima, Takahiro Nobukuni, Hayato Anzawa, Li Bin, Miyuki Tsuda, Kazuki Kumada, Hisaaki Kudo, Takahiro Terakawa, Akihito Otsuki, Kengo Kinoshita, Riu Yamashita, Naoko Minegishi, Masayuki Yamamoto

    Free Radical Biology and Medicine　161　71-83　2020年12月

    出版者・発行元： Elsevier BV

    DOI： 10.1016/j.freeradbiomed.2020.09.023 　

    ISSN：0891-5849

  19. Identification of dominant transcripts in oxidative stress response by a full-length transcriptome analysis

    Akihito Otsuki, Yasunobu Okamura, Yuichi Aoki, Noriko Ishida, Kazuki Kumada, Naoko Minegishi, Fumiki Katsuoka, Kengo Kinoshita, Masayuki Yamamoto

    Molecular and Cellular Biology　2020年11月9日

    出版者・発行元： American Society for Microbiology

    DOI： 10.1128/mcb.00472-20 　

    ISSN：0270-7306

    eISSN：1098-5549

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    Our body responds to environmental stress by changing the expression levels of a series of cytoprotective enzymes/proteins through multilayered regulatory mechanisms, including the KEAP1-NRF2 system. While NRF2 upregulates the expression of many cytoprotective genes, there are fundamental limitations in short-read RNA sequencing (RNA-Seq), resulting in confusion regarding interpreting the effectiveness of cytoprotective gene induction at transcript level. To precisely delineate isoform usage in the stress response, we conducted independent full-length transcriptome profiling (isoform sequencing; Iso-Seq) analyses of lymphoblastoid cells from three volunteers under normal and electrophilic stress-induced conditions. We first determined the first exon usage in <italic>KEAP1</italic> and <italic>NFE2L2</italic> (encoding NRF2) and found the presence of transcript diversity. We then examined changes in isoform usage of NRF2 target genes under stress conditions and identified a few isoforms dominantly expressed in the majority of NRF2 target genes. The expression levels of isoforms determined by Iso-Seq analyses showed striking differences from those determined by short-read RNA-Seq; the latter could be misleading in regards to the abundance of transcripts. These results support that transcript usage is tightly regulated to produce functional proteins under electrophilic stress. Our present study strongly argues that there are important benefits that can be achieved by long-read transcriptome sequencing.

  20. Design and Progress of Oral Health Examinations in the Tohoku Medical Megabank Project

    Akito Tsuboi, Hiroyuki Matsui, Naru Shiraishi, Takahisa Murakami, Akihito Otsuki, Junko Kawashima, Tomomi Kiyama, Toru Tamahara, Maki Goto, Shihoko Koyama, Junichi Sugawara, Eiichi N. Kodama, Hirohito Metoki, Atsushi Hozawa, Shinichi Kuriyama, Hiroaki Tomita, Masahiro Kikuya, Naoko Minegishi, Kichiya Suzuki, Seizo Koshiba, Gen Tamiya, Nobuo Fuse, Yuichi Aoki, Takako Takai-Igarashi, Soichi Ogishima, Tomohiro Nakamura, Mika Sakurai-Yageta, Fuji Nagami, Kengo Kinoshita, Shigeo Kure, Ritsuko Shimizu, Keiichi Sasaki, Masayuki Yamamoto

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　251　(2)　97-115　2020年6月

    DOI： 10.1620/tjem.251.97 　

    ISSN：0040-8727

    eISSN：1349-3329

  21. Impacts of NRF2 activation in non-small-cell lung cancer cell lines on extracellular metabolites. 国際誌

    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

    DOI： 10.1111/cas.14278 　

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    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.

  22. Oral Microbiome Analysis in Prospective Genome Cohort Studies of the Tohoku Medical Megabank Project. 国際誌

    Sakae Saito, Yuichi Aoki, Toru Tamahara, Maki Goto, Hiroyuki Matsui, Junko Kawashima, Inaho Danjoh, Atsushi Hozawa, Shinichi Kuriyama, Yoichi Suzuki, Nobuo Fuse, Shigeo Kure, Riu Yamashita, Osamu Tanabe, Naoko Minegishi, Kengo Kinoshita, Akito Tsuboi, Ritsuko Shimizu, Masayuki Yamamoto

    Frontiers in cellular and infection microbiology　10　604596-604596　2020年

    DOI： 10.3389/fcimb.2020.604596 　

    詳細を見る 詳細を閉じる

    A baseline oral microbiome study of the Tohoku Medical Megabank Organization (TMM) was planned to characterize the profile of the oral microbiome in the Japanese population. The study also aimed to clarify risk factors for multifactorial diseases by integrated analysis of the oral microbiome and host genome/omics information. From 2013 to 2016, we collected three types of oral biospecimens, saliva, supragingival plaque, and tongue swab, from a total of 25,101 participants who had a dental examination in TMM. In this study, we used two independent cohorts; the Community-Based Cohort and Birth and Three-Generation Cohort as discovery and validation cohorts, respectively, and we selected participants examined by a single dentist. We found through the 16S ribosomal RNA gene sequencing analysis of 834 participants of the Community-Based Cohort Study that there are differences in the microbial composition and community structure between saliva and plaque. The species diversities in both saliva and plaque were increased in correlation with the severity of periodontal disease. These results were nicely reproduced in the analysis of 455 participants of the Birth and Three-Generation Cohort Study. In addition, strong positive and negative associations of microbial taxa in both plaque and saliva with periodontitis-associated biofilm formation were detected by co-occurrence network analysis. The classes Actinobacteria and Bacilli, including oral health-associated bacterial species, showed a positive correlation in saliva. These results revealed differences in microbial composition and community structure between saliva and plaque and a correlation between microbial species and the severity of periodontal disease. We expect that the large database of the oral microbiome in the TMM biobank will help in the discovery of novel targets for the treatment and prevention of oral diseases, as well as for the discovery of therapeutic and/or preventive targets of systemic diseases.

  23. 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　92回　[1T12a-04]　2019年9月

    出版者・発行元： (公社)日本生化学会

  24. 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

  25. COXPRESdb v7: a gene coexpression database for 11 animal species supported by 23 coexpression platforms for technical evaluation and evolutionary inference 査読有り

    Takeshi Obayashi, Yuki Kagaya, Yuichi Aoki, Shu Tadaka, Kengo Kinoshita

    Nucleic Acids Research　2018年11月

    出版者・発行元： Oxford University Press ({OUP})

    DOI： 10.1093/nar/gky1155 　

    ISSN：0305-1048

  26. 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　91回　[3T14a-314)]　2018年9月

    出版者・発行元： (公社)日本生化学会

  27. 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

  28. 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　2017年10月

    出版者・発行元： Oxford University Press ({OUP})

    DOI： 10.1093/nar/gkx978 　

    ISSN：0305-1048

  29. Root-Knot and Cyst Nematodes Activate Procambium-Associated Genes in Arabidopsis Roots 査読有り

    Yasuka L. Yamaguchi, Reira Suzuki, Javier Cabrera, Satoru Nakagami, Tomomi Sagara, Chika Ejima, Ryosuke Sano, Yuichi Aoki, Rocio Olmo, Tetsuya Kurata, Takeshi Obayashi, Taku Demura, Takashi Ishida, Carolina Escobar, Shinichiro Sawa

    FRONTIERS IN PLANT SCIENCE　8　2017年7月

    DOI： 10.3389/fpls.2017.01195 　

    ISSN：1664-462X

  30. ATTED-II in 2018: A Plant Coexpression Database Based on Investigation of the Statistical Property of the Mutual Rank Index 査読有り

    Takeshi Obayashi, Yuichi Aoki, Shu Tadaka, Yuki Kagaya, Kengo Kinoshita

    Plant and Cell Physiology　59　(1)　e3　2017年

    出版者・発行元： Oxford University Press ({OUP})

    DOI： 10.1093/pcp/pcx191 　

    ISSN：0032-0781

  31. Identification and reconstitution of the rubber biosynthetic machinery on rubber particles from Hevea brasiliensis 査読有り

    Satoshi Yamashita, Haruhiko Yamaguchi, Toshiyuki Waki, Yuichi Aoki, Makie Mizuno, Fumihiro Yanbe, Tomoki Ishii, Ayuta Funaki, Yuzuru Tozawa, Yukino Miyagi-Inoue, Kazuhisa Fushihara, Toru Nakayama, Seiji Takahashi

    ELIFE　5　e19022　2016年10月

    DOI： 10.7554/eLife.19022 　

    ISSN：2050-084X

  32. ALCOdb: Gene Coexpression Database for Microalgae 査読有り

    Yuichi Aoki, Yasunobu Okamura, Hiroyuki Ohta, Kengo Kinoshita, Takeshi Obayashi

    PLANT AND CELL PHYSIOLOGY　57　(1)　e3　2016年1月

    DOI： 10.1093/pcp/pcv190 　

    ISSN：0032-0781

    eISSN：1471-9053

  33. ATTED-II in 2016: A Plant Coexpression Database Towards Lineage-Specific Coexpression 査読有り

    Yuichi Aoki, Yasunobu Okamura, Shu Tadaka, Kengo Kinoshita, Takeshi Obayashi

    Plant and Cell Physiology　57　(1)　e5　2015年11月

    出版者・発行元： Oxford University Press ({OUP})

    DOI： 10.1093/pcp/pcv165 　

    ISSN：0032-0781

  34. COXPRESdb in 2015: coexpression database for animal species by DNA-microarray and RNAseq-based expression data with multiple quality assessment systems. 査読有り

    Okamura Y, Aoki Y, Obayashi T, Tadaka S, Ito S, Narise T, Kinoshita K

    Nucleic acids research　43　(Database issue)　D82-6　2015年1月

    DOI： 10.1093/nar/gku1163 　

    ISSN：0305-1048

  35. COXPRESdb in 2015: coexpression database for animal species by DNA-microarray and RNAseq-based expression data with multiple quality assessment systems 査読有り

    Yasunobu Okamura, Yuichi Aoki, Takeshi Obayashi, Shu Tadaka, Satoshi Ito, Takafumi Narise, Kengo Kinoshita

    Nucleic Acids Research　43　(D1)　D82　2014年11月

    出版者・発行元： Oxford University Press ({OUP})

    DOI： 10.1093/nar/gku1163 　

    ISSN：1362-4962

  36. ATTED-II in 2014: Evaluation of Gene Coexpression in Agriculturally Important Plants 査読有り

    Takeshi Obayashi, Yasunobu Okamura, Satoshi Ito, Shu Tadaka, Yuichi Aoki, Matsuyuki Shirota, Kengo Kinoshita

    Plant and Cell Physiology　55　(1)　e6　2014年1月

    出版者・発行元： Oxford University Press ({OUP})

    DOI： 10.1093/pcp/pct178 　

    ISSN：1471-9053

  37. ATTED-II in 2014: Evaluation of Gene Coexpression in Agriculturally Important Plants 査読有り

    Takeshi Obayashi, Yasunobu Okamura, Satoshi Ito, Shu Tadaka, Yuichi Aoki, Matsuyuki Shirota, Kengo Kinoshita

    PLANT AND CELL PHYSIOLOGY　55　(1)　e6　2014年1月

    DOI： 10.1093/pcp/pct178 　

    ISSN：0032-0781

    eISSN：1471-9053

︎全件表示 ︎最初の5件までを表示

MISC 5

  1. 卵巣癌における口腔内メタゲノム解析によるバイオマーカーの探索

    橋本千明, 島田宗昭, 島田宗昭, 齋藤さかえ, 玉原亨, 李賓, 菱沼英史, 青木裕一, 渋谷祐介, 久木元詩央香, 栃木実佳子, 萩原達也, 清水孝規, 工藤敬, 湊純子, 石橋ますみ, 重田昌吾, 徳永英樹, 清水律子, 八重樫伸生, 八重樫伸生

    日本婦人科腫瘍学会学術講演会プログラム・抄録集(Web)　66th　2024年

  2. 血中代謝プロファイルに遺伝・環境要因が与える影響の解析

    小柴生造, 小柴生造, 元池育子, 元池育子, 菱沼英史, 菱沼英史, 青木裕一, 櫻井美由紀, 佐藤允治, 七谷圭, 七谷圭, 田高周, 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)　96th　2023年

  3. 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, 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

  4. 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

  5. 遺伝子共発現ネットワークにおけるタンパク質細胞内局在の影響

    青木裕一, 青木裕一, 大林武, 木下賢吾, 木下賢吾

    日本生化学会大会(Web)　90th　2017年

共同研究・競争的資金等の研究課題 5

  1. メタゲノム解析による人体の全消化管細菌叢の同定と臨床応用へのアプローチ

    石沢 興太, 菅野 武, 青木 裕一, 高山 真

    2023年4月1日 ～ 2028年3月31日

  2. 日本産針葉樹全種の遺伝的多様性統合解析

    陶山 佳久, 北村 系子, 津村 義彦, Worth James, 内山 憲太郎, 青木 裕一, 戸丸 信弘, 岩泉 正和, 高橋 大樹, 逢沢 峰昭, 玉城 聡

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

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

    研究機関：Tohoku University

    2023年4月1日 ～ 2026年3月31日

  3. 難分解性nanoプラステック粒子が引き起こす微細藻の生理異常と種スペクトラム解析

    大濱 武, 林 八寿子, 右手 浩一, 青木 裕一

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

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

    研究機関：Kochi University of Technology

    2019年4月1日 ～ 2022年3月31日

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    イソブチルシアノアクリレートをモノマーとするナノ粒子（iBCA-NP），エチル粒子(ECA-NP)，メチル粒子(MCA-NP)，イソプロピル粒子(iPCA-NP)を、Tween 80を用いて作成した。これらの粒子が持つ増殖阻害能を細菌，酵母，緑藻を用いて検証した。iBCA-NPがもっとも弱い細胞増殖阻害能を示すことが多く，ECA-NPが最も多くの生物種に対して，細胞死誘導能を示した。iPCA-NPは， iBCA-NPやECA-NP爆露が全く生育に影響を及ぼさないような緑藻に対しても，強い細胞増殖阻害を示す場合もあった。ナノ粒子暴露の効果は，近縁種の間でも全く異なるという例があった。

  4. 狭波長LED照射に応答する植物メタボロームのデジタルケミカルマッピング

    草野 都, 立川 仁典, 青木 裕一, 福島 敦史

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

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

    研究機関：University of Tsukuba

    2019年4月1日 ～ 2022年3月31日

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    最終年度では研究成果の論文化を目指し、シロイヌナズナの葉で生産される11種類のアントシアニンに着目した。我々が開発した半経験的分子軌道計算法（桑畑ら、2019）を用い、各化合物のUVスペクトルを予測し、実測値を比較した。その結果、予測値は実測値と類似した波長および吸収強度を示した。このことから、半経験的分子軌道計算法によるUVスペクトル予測はアントシアニンの置換基付加によるUVスペクトルの形状および吸収強度の変化を十分捉えることができることを明らかにした。本成果は現在論文投稿準備中である。 昨年度採択された「先端ゲノム支援」により得られた異なる光質処理を行ったサニーレタスサンプルから得たRNA-seqデータと統合するため、同一条件下で栽培したサンプルを用いてメタボローム解析データの取得を行った。現在得たデータを解析中である。

  5. ヌクレオソーム配置を介した遺伝子発現制御機構の解明：ゲノム高次構造と遺伝子共発現

    青木 裕一

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

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

    研究機関：Tohoku University

    2015年4月1日 ～ 2018年3月31日

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    本研究では、モデル植物シロイヌナズナを対象に、遺伝子発現パターンが類似する遺伝子群（共発現遺伝子群）をゲノム情報から推定する手法の開発に取り組んだ。遺伝子発現制御に影響を及ぼす高次のゲノム特徴量としてヌクレオソームポジショニングに着目して解析を進めた結果、転写開始点近傍のヌクレオソーム形成状態が遺伝子の平均発現量に強く影響することや、平均発現量が同程度の遺伝子同士が強く共発現することを明らかにした。さらに、タンパク質コード領域の進化的新旧度とヌクレオソーム形成状態が強く相関することを発見し、遺伝子発現制御と遺伝子機能の両面から遺伝子共発現ネットワークの形成原理を理解するための基盤を構築した。