研究者詳細 - 松井　佑介

論文 - 松井　佑介

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D3M：Detection of differential distributions of methylation levels. 招待有り査読有り

Yusuke Matsui, Masahiro Mizuta, Satoshi Ito , Satoru Miyano, Teppei Shimamura

Bioinformatics 32 巻 ( 15 ) 頁： 2248 - 2255 2016年8月

Predicting Alzheimer's Cognitive Resilience Score: A Comparative Study of Machine Learning Models Using RNA-seq Data

Akihiro Kitani, Yusuke Matsui

2024年8月

担当区分：責任著者出版者・発行元：Cold Spring Harbor Laboratory

Alzheimer's disease (AD) is an important research topic. While amyloid plaques and neurofibrillary tangles are hallmark pathological features of AD, cognitive resilience (CR) is a phenomenon where cognitive function remains preserved despite the presence of these pathological features. This study aimed to construct and compare predictive machine learning models for CR scores using RNA-seq data from the Religious Orders Study and Memory and Aging Project (ROSMAP) and Mount Sinai Brain Bank (MSBB) cohorts. We evaluated support vector regression (SVR), random forest, XGBoost, linear, and transformer-based models. The SVR model exhibited the best performance, with contributing genes identified using Shapley additive explanations (SHAP) scores, providing insights into biological pathways associated with CR. Finally, we developed a tool called the resilience gene analyzer (REGA), which visualizes SHAP scores to interpret the contributions of individual genes to CR. REGA is available at https://igcore.cloud/GerOmics/REsilienceGeneAnalyzer/.

DOI： 10.1101/2024.08.25.609610

HuTAge: a Comprehensive Human Tissue- and Cell-specific Ageing Signature Atlas

Koichi Himori, Zhang Bingyuan, Kazuki Hatta, Yusuke Matsui

2024年8月

担当区分：最終著者出版者・発行元：Cold Spring Harbor Laboratory

Abstract

Summary

Ageing is a complex process that involves interorgan and intercellular interactions. To obtain a clear understanding of ageing, cross-tissue single-cell data resources are required. However, a complete resource for humans is not available. To bridge this gap, we developed HuTAge, a comprehensive resource that integrates cross-tissue age-related information from The Genotype-Tissue Expression project with cross-tissue single-cell information from Tabula Sapiens to provide human tissue- and cell-specific ageing molecular information.

Availability and Implementation

HuTAge is implemented within an R Shiny application and can be freely accessed athttps://igcore.cloud/GerOmics/HuTAge/home. The source code is available athttps://github.com/matsui-lab/HuTAge.

Contact

himori.koichi.b5@f.mail.nagoya-u.ac.jp

DOI： 10.1101/2024.08.07.606269

Toward a systems glycogenomics approach to understanding diseases 招待有り

松井佑介

Glycoforum 27 巻 ( 4 ) 頁： A12 2024年8月

A Computational Approach to Interpreting the Embedding Space of Dimension Reduction

Bingyuan Zhang, Kohei Uno, Hayata Kodama, Koichi Himori, Yusuke Matsui

2024年6月

担当区分：最終著者,　責任著者出版者・発行元：Cold Spring Harbor Laboratory

Summary

Nonlinear dimension reduction methods are widely applied in studies analyzing gene and protein expression, by revealing patterns of discrete groups and continuous orders in high-dimensional data. However, the tools are limited to understanding the obtained embedding structures of biological mechanisms, hindering the full exploitation of data. Here, we propose a novel framework to interpret embedding systematically by identifying and mapping associated biological functions. The method performs statistical tests and visualizes significantly enriched functions essential for the organization of the embedding structure, by applying it to the embedding results of two datasets: the Genotype Tissue Expression dataset and aCaenorhabditis elegansembryogenesis dataset, one capturing distinct cluster structures and the other capturing continuous developmental trajectories. We identified the associated functions for interpreting the two embeddings and confirmed it as a useful explainable AI tool in exploratory data analysis by providing annotations to the embedding space.

DOI： 10.1101/2024.06.23.600292

GPNMB+ microglia moderate the amyloid beta-tau interaction in early Alzheimer’s disease

Akihiro Kitani, Yusuke Matsui

2024年6月

担当区分：最終著者,　責任著者出版者・発行元：Cold Spring Harbor Laboratory

Summary

Although interactions between amyloid-beta (Aβ) and tau proteins have been implicated in Alzheimer’s disease (AD), the detailed mechanisms by which these interactions contribute to disease progression remain unclear. In this study, we evaluated proteomics and protein–protein interaction data using BIONC, a deep learning-based network integration method to investigate factors moderating the effects of the Aβ-tau interaction in mild cognitive impairment and early-stage AD. Our results suggested that astrocytes and GPNMB+ microglia moderate the Aβ-tau interaction. Based on linear regression with histopathological and gene expression data, GFAP and IBA1 levels andGPNMBgene expression positively contributed to the interaction of tau with Aβ in non-dementia cases, replicating the results of the network analysis. These findings indicate that GPNMB+ microglia moderate the Aβ-tau interaction in early AD and therefore are a novel therapeutic target.

Graphical Abstract

DOI： 10.1101/2024.06.14.599092

Evaluating Desk-Assisted Standing Techniques for Simulated Pregnant Conditions: An Experimental Study Using a Maternity-Simulation Jacket

Kohei Uno, Kako Tsukioka, Hibiki Sakata, Tomoe Inoue-Hirakawa, Yusuke Matsui

Healthcare 12 巻 ( 9 ) 頁： 931 - 931 2024年5月

担当区分：最終著者掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

Lower back pain, a common issue among pregnant women, often complicates daily activities like standing up from a chair. Therefore, research into the standing motion of pregnant women is important, and many research studies have already been conducted. However, many of these studies were conducted in highly controlled environments, overlooking everyday scenarios such as using a desk for support when standing up, and their effects have not been adequately tested. To address this gap, we measured multimodal signals for a sit-to-stand (STS) movement with hand assistance and verified the changes using a t-test. To avoid imposing strain on pregnant women, we used 10 non-diseased young adults who wore jackets designed to simulate pregnancy conditions, thus allowing for more comprehensive and rigorous experimentation. We attached surface electromyography (sEMG) sensors to the erector spinae muscles of participants and measured changes in muscle activity, skeletal positioning, and center of pressure both before and after wearing a Maternity-Simulation Jacket. Our analysis showed that the jacket successfully mimicked key aspects of the movement patterns typical in pregnant women. These results highlight the possibility of developing practical strategies that more accurately mirror the real-life scenarios met by pregnant women, enriching the current research on their STS movement.

DOI： 10.3390/healthcare12090931

Systematic identification of exercise-induced anti-aging processes involving intron retention

Hayata Kodama, Hirotaka Ijima, Yusuke Matsui

2024年4月

担当区分：最終著者,　責任著者出版者・発行元：Cold Spring Harbor Laboratory

Abstract

Exercise is one of the most promising anti-aging interventions for maintaining skeletal muscle health in older adults. Nine “Aging Hallmarks”, proposed by López-Otín, offer insights into the aging process; however, the link between these hallmarks and exercise is not fully elucidated. In this study, we conducted a systematic multi-omics analysis of skeletal muscles, focusing on aging and exercise, based on gene signatures for aging hallmarks. It is posited that mRNA splicing activity, linked to genomic instability, constitutes a fundamental hallmark of aging, and it exhibits divergent expression patterns in response to aging and exercise. Additionally, we analysed splicing events and discovered that intron retention (IR) is significantly impacted by aging, exhibiting contrasting changes to those induced by resistance training in the older cohort. The isoforms characterised by IR are notably enriched in mitochondrial functions. Conclusively, our results underscore the significance of splicing mechanisms as a novel aspect of aging hallmarks in skeletal muscles and propose a new mechanism by which exercise exerts its anti-aging effects on skeletal muscles through intron retention.

Key points summary

Skeletal muscle aging involves significant structural and functional changes, including loss of muscle mass, decline in strength, and mitochondrial dysfunction, all influenced by genomic instability.

Exercise has been identified as a key intervention that counters genomic instability and modulates mRNA splicing patterns, particularly through the regulation of Intron Retention, to mitigate aging effects in skeletal muscle.

We reveal the novel role of IR, especially in principal isoforms, where it is linked to critical cellular processes like mitochondrial function, suggesting a targeted pathway through which exercise exerts its anti-aging effects.

The findings provide new insights into the molecular mechanisms underlying the beneficial effects of exercise on aging skeletal muscle.

This study lays the groundwork for future research on exercise-induced modulation of mRNA splicing as a therapeutic strategy for aging and potentially age-related diseases, pointing towards a significant shift in how we approach aging intervention strategies.

DOI： 10.1101/2024.04.25.591048

BRAFV600E Promotes Anchorage-Independent Growth but Inhibits Anchorage-Dependent Growth in hTERT / Cdk4-Immortalized Normal Human Bronchial Epithelial Cells

Nao Muraki, Nozomi Kawabe, Ayano Ohashi, Kanna Umeda, Masahito Katsuda, Aya Tomatsu, Mikina Yoshida, Kazuki Komeda, John D. Minna, Ichidai Tanaka, Masahiro Morise, Miyoko Matsushima, Yusuke Matsui, Tsutomu Kawabe, Mitsuo Sato

Experimental Cell Research 頁： 114057 - 114057 2024年4月

Network-based cytokine inference implicates Oncostatin M as a driver of an inflammation phenotype in knee osteoarthritis 招待有り査読有り国際共著

Iijima H, Zhang F, Ambrosio F, Matsui Y.

Aging Cell 頁： e14043 2024年2月

Single-cell Glycogenomics Deciphers Links Between Altered Transcriptional Regulation and Aberrant Glycosylation in Alzheimer’s Disease

Yusuke Matsui, Akira Togayachi, Kazuma Sakamoto, Kiyohiko Angata, Kenji Kadomatsu, Shoko Nishihara

2023年12月

担当区分：筆頭著者,　責任著者出版者・発行元：Cold Spring Harbor Laboratory

Summary

Glycosylation is increasingly recognized as a potential new therapeutic target in Alzheimer’s disease. In recent years, evidence for Alzheimer’s disease-specific glycoproteins has been established. However, the mechanisms of their dysregulation, including tissue and cell type specificity, are not fully understood. We aimed to explore upstream regulators of aberrant glycosylation by integrating multiple data sources and using a glycogenomics approach. We identified dysregulation by the glycosyltransferase PLOD3 in oligodendrocytes as an upstream regulator in cerebral vessels, and found that it is involved in COL4A5 synthesis, which is strongly correlated with amyloid fiber formation. Furthermore, COL4A5 was suggested to interact with astrocytes via ECM receptors as a ligand. This study suggests directions for new therapeutic strategies for Alzheimer’s disease targeting glycosyltransferases.

Graphical Abstract

DOI： 10.1101/2023.12.25.573290

Network-based systematic dissection of exercise-induced inhibition of myosteatosis in older individuals. 査読有り国際共著

Iijima H, Ambrosio F, Matsui Y.

J Physiol. 2023年12月

Unbiased estimation of the population-level motor module

Yusuke Matsui, Kohei Uno, Ippei Nojima

2023年6月

担当区分：筆頭著者,　責任著者出版者・発行元：Cold Spring Harbor Laboratory

Summary

Motor module is a functional neurophysiological command for muscle coordination. In clinical settings, population-level characterization and comparison of motor modules are necessary to evaluate pathophysiological mechanisms and intervention effects. Previous studies have estimated individual motor modules and then compared them, but the validity of capturing the distribution of the latent population has not been fully understood. Our study aimed to address this issue by investigating the accuracy of estimating the population mean of motor modules. Through simulation experiments, we found that previous individual-based approach did not converge regardless of sample size and was vulnerable to noise. We developed an unbiased estimation algorithm using the framework of functional data analysis, which significantly improved estimation accuracy. Our findings highlight statistical challenges for motor module analysis and suggest the need for further research on new computational algorithms using large-scale clinical data.

Graphical Abstract

DOI： 10.1101/2023.06.25.23291878

Pgc-1α is an exercise-responsive regulator of myosteatosis in older individuals

Hirotaka Iijima, Fabrisia Ambrosio, Yusuke Matsui

2023年2月

担当区分：最終著者,　責任著者出版者・発行元：Cold Spring Harbor Laboratory

SUMMARY

Accumulated fat in skeletal muscle, common in sedentary older individuals, compromises skeletal muscle health and function. Mechanistic understanding ofhowphysical activity levels dictate fat accumulation represents a critical step towards establishment of therapies that promote healthy aging. Using a network paradigm that characterized the transcriptomic response of aged muscle to exercise versus immobilization protocols, this study uncovered a novel molecular cascade that regulates the fate of fibro-adipogenic progenitors (FAPs), the cell population primarily responsible for the fat accumulation. Specifically, gene set enrichment analyses (GSEA) with network propagation revealedPgc1α as a functional hub of a large gene regulatory network underlying the regulation of FAPs by physical activity. Integratedin silicoandin situapproaches to inducePgc-1α overexpression promoted mitochondrial fatty acid oxidation and inhibited FAPs adipogenesis. These findings suggest thatPgc1α is a master regulator by which physical activity regulates fat accumulation in aged skeletal muscle.

GRAPHICAL ABSTRUCT

DOI： 10.1101/2023.02.07.527478

Network-based cytokine inference implicates Oncostatin M as a driver for inflammation phenotype of knee osteoarthritis

Hirotaka Iijima, Fan Zhang, Fabrisia Ambrosio, Yusuke Matsui

2023年1月

担当区分：責任著者出版者・発行元：Cold Spring Harbor Laboratory

SUMMARY

Inflammatory cytokines released by the synovium after trauma disturb the gene regulatory network and have been implicated in the pathophysiology of osteoarthritis. A mechanistic understanding of how aging perturbs this process can help identify novel interventions. Here, we introduced network paradigms to simulate cytokine-mediated pathological communication between the synovium and cartilage. Cartilage-specific network analysis of injured young and aged murine knees revealed aberrant matrix remodeling as a transcriptomic response unique to aged knees displaying accelerated cartilage degradation. Next, network-based cytokine inference with pharmacological manipulation uncovered IL6 family member, Oncostatin M, as a driver for the aberrant matrix remodeling. By implementing a phenotypic drug discovery approach, we identified that the activation of Oncostatin M recapitulated “inflammation” phenotype of knee osteoarthritis and highlighted high-value targets for drug development and repurposing. These findings offer translational opportunities targeting the inflammation-driven osteoarthritis phenotype.

GRAPHICAL ABSTRACT

DOI： 10.1101/2023.01.24.525463

Types of anomalies in two-dimensional video-based gait analysis in uncontrolled environments 招待有り査読有り

Yuki Sugiyama ,Kohei Uno ,Yusuke Matsui

PLoS Computational Biology 2023年1月

理学療法におけるデータサイエンスとAIの利活用と課題理学療法の教育分野におけるデータサイエンスとAIの利活用と課題招待有り査読有り

松井佑介

理学療法 2022年4月

Meta-analysis integrated with multi-omics data analysis to elucidate pathogenic mechanisms of age-related knee osteoarthritis in mice 査読有り国際共著

Hirotaka Iijima, Gabrielle Gilmer, Kai Wang, Sruthi Sivakumar, Christopher Evans, Yusuke Matsui, Fabrisia Ambrosio

The journals of gerontology. Series A, Biological sciences and medical sciences 2022年3月

Pan-cancer methylome analysis for cancer diagnosis and classification of cancer cell of origin. 招待有り査読有り

Dai Shimizu, Kenzui Taniue, Yusuke Matsui, Hiroshi Haeno, Hiromitsu Araki, Fumihito Miura, Mitsuko Fukunaga, Kenji Shiraishi, Yuji Miyamoto, Seiichi Tsukamoto, Aya Komine, Yuta Kobayashi, Akihiro Kitagawa, Yukihiro Yoshikawa, Kuniaki Sato, Tomoko Saito, Shuhei Ito, Takaaki Masuda, Atsushi Niida, Makoto Suzuki, Hideo Baba, Takashi Ito, Nobuyoshi Akimitsu, Yasuhiro Kodera, Koshi Mimori

Cancer gene therapy 2021年11月

Increased BUB1B/BUBR1 expression contributes to aberrant DNA repair activity leading to resistance to DNA-damaging agents. 招待有り査読有り

Kazumasa Komura, Teruo Inamoto, Takuya Tsujino, Yusuke Matsui, Tsuyoshi Konuma, Kazuki Nishimura, Taizo Uchimoto, Takeshi Tsutsumi, Tomohisa Matsunaga, Ryoichi Maenosono, Yuki Yoshikawa, Kohei Taniguchi, Tomohito Tanaka, Hirofumi Uehara, Koichi Hirata, Hajime Hirano, Hayahito Nomi, Yoshinobu Hirose, Fumihito Ono, Haruhito Azuma

Oncogene 2021年9月

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