研究者詳細 - 松井　佑介

論文 - 松井　佑介

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Improved Prediction Accuracy for Late-Onset Preeclampsia Using cfRNA Profiles: A Comparative Study of Marker Selection Strategies. 招待有り査読有り国際誌 Open Access

Akiha Nakano, Kohei Uno, Yusuke Matsui

Healthcare (Basel, Switzerland) 13 巻 ( 10 ) 2025年5月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Late-onset pre-eclampsia (LO-PE) remains difficult to predict because placental angiogenic markers perform poorly once maternal cardiometabolic factors dominate. Methods: We reanalyzed a publicly available cell-free RNA (cfRNA) cohort (12 EO-PE, 12 LO-PE, and 24 matched controls). After RNA-seq normalization, we derived LO-PE candidate genes using (i) differential expression and (ii) elastic-net feature selection. Predictive accuracy was assessed with nested Monte-Carlo cross-validation (10 × 70/30 outer splits; 5-fold inner grid-search for λ). Results: The best LO-PE elastic-net model achieved a mean ± SD AUROC of 0.88 ± 0.08 and F1 of 0.73 ± 0.17-substantially higher than an EO-derived baseline applied to the same samples (AUROC ≈ 0.69). Enrichment analysis highlighted immune-tolerance and metabolic pathways; three genes (HLA-G, IL17RB, and KLRC4) recurred across >50% of cross-validation repeats. Conclusions: Plasma cfRNA signatures can outperform existing EO-based screens for LO-PE and nominate biologically plausible markers of immune and metabolic dysregulation. Because the present dataset is small (n = 48) and underpowered for single-gene claims, external validation in larger, multicenter cohorts is essential before clinical translation.

DOI： 10.3390/healthcare13101162

Open Access

PubMed

HuTAge: a comprehensive human tissue- and cell-specific ageing signature atlas

Koichi Himori, Zhang Bingyuan, Kazuki Hatta, Yusuke Matsui

Bioinformatics Advances 5 巻 ( 1 ) 2025年4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：Oxford University Press (OUP)

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 at https://igcore.cloud/GerOmics/HuTAge/home. The source code is available at https://github.com/matsui-lab/HuTAge.

DOI： 10.1093/bioadv/vbaf072

その他リンク： https://academic.oup.com/bioinformaticsadvances/article-pdf/5/1/vbaf072/62856785/vbaf072.pdf

Integrative network analysis reveals novel moderators of Aβ-Tau interaction in Alzheimer's disease. 査読有り国際誌 Open Access

Akihiro Kitani, Yusuke Matsui

Alzheimer's research & therapy 17 巻 ( 1 ) 頁： 70 - 70 2025年4月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Although interactions between amyloid-beta and tau proteins have been implicated in Alzheimer's disease (AD), the precise mechanisms by which these interactions contribute to disease progression are not yet fully understood. Moreover, despite the growing application of deep learning in various biomedical fields, its application in integrating networks to analyze disease mechanisms in AD research remains limited. In this study, we employed BIONIC, a deep learning-based network integration method, to integrate proteomics and protein-protein interaction data, with an aim to uncover factors that moderate the effects of the Aβ-tau interaction on mild cognitive impairment (MCI) and early-stage AD. METHODS: Proteomic data from the ROSMAP cohort were integrated with protein-protein interaction (PPI) data using a Deep Learning-based model. Linear regression analysis was applied to histopathological and gene expression data, and mutual information was used to detect moderating factors. Statistical significance was determined using the Benjamini-Hochberg correction (p < 0.05). RESULTS: 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 and GPNMB gene expression positively contributed to the interaction of tau with Aβ in non-dementia cases, replicating the results of the network analysis. CONCLUSIONS: These findings suggest that GPNMB + microglia moderate the Aβ-tau interaction in early AD and therefore are a novel therapeutic target. To facilitate further research, we have made the integrated network available as a visualization tool for the scientific community (URL: https://igcore.cloud/GerOmics/AlzPPMap ).

DOI： 10.1186/s13195-025-01705-x

Open Access

PubMed

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

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

The Human Glycome Atlas Project for cataloging all glycan-related omics data in human. 査読有り国際誌 Open Access

Kiyoko F Aoki-Kinoshita, Hiromune Ando, Kiyohiko Angata, Morihisa Fujita, Jun-Ichi Furukawa, Hiroyuki Kaji, Koichi Kato, Ken Kitajima, Yasuhiko Kizuka, Yusuke Matsui, Kazuki Nakajima, Shoko Nishihara, Tetsuya Okajima, Kazuma Sakamoto, Chihiro Sato, Morten Thaysen-Andersen, Akira Togayachi, Hirokazu Yagi, Kenji Kadomatsu

Glycobiology 2024年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

The Human Glycome Atlas (HGA) Project was launched in April 2023, spearheaded by three Japanese institutes: the Tokai National Higher Education and Research System, the National Institutes of Natural Sciences, and Soka University. This was the first time that a field in the life sciences was adopted by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) for a Large-scale Academic Frontiers Promotion Project. This project aims to construct a knowledgebase of human glycans and glycoproteins as a standard for the human glycome. A high-throughput pipeline for comprehensively analyzing 20,000 blood samples in its first five years is planned, at which time an access-controlled version of a human glycomics knowledgebase, called TOHSA, will be released. By the end of the final tenth year, TOHSA will provide a central resource linking human glycan data with other omics data including disease-related information.

DOI： 10.1093/glycob/cwae052

Open Access

PubMed

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 Open Access

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 Open Access

Iijima H, Ambrosio F, Matsui Y.

J Physiol. 2023年12月

Network-based systematic dissection of exercise-induced inhibition of myosteatosis in older individuals. 国際誌 Open Access

Hirotaka Iijima, Fabrisia Ambrosio, Yusuke Matsui

The Journal of physiology 2023年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Accumulated fat in skeletal muscle (i.e. myosteatosis), common in sedentary older individuals, compromises skeletal muscle health and function. A mechanistic understanding of how physical activity levels dictate fat accumulation represents a critical step towards establishment of therapies that promote healthy ageing. Using a network medicine paradigm that characterized the transcriptomic response of aged muscle to exercise versus immobilization protocols, this study explored the shared molecular cascade that regulates the fate of fibro-adipogenic progenitors (FAPs), the cell population primarily responsible for fat accumulation. Specifically, gene set enrichment analyses with network propagation revealed Pgc-1α as a functional hub of a large gene regulatory network underlying the regulation of FAPs by physical activity in aged muscle, but not in young counterparts. Integrated in silico and in situ approaches to induce Pgc-1α overexpression in aged muscle promoted mitochondrial fatty acid oxidation and inhibited FAP adipogenesis. These findings suggest that the Pgc-1α-mitochondrial fatty acid oxidation axis is a shared mechanism by which physical activity regulates age-related myosteatosis. The network medicine paradigm introduced provides mechanistic insight into exercise adaptation in elderly skeletal muscle and offers translational opportunities to advance exercise prescription for older populations. KEY POINTS: Fat accumulation is a quintessential feature of aged skeletal muscle. While increasing physical activity levels has been proposed as an effective strategy to reduce the fat in skeletal muscle (i.e. myosteatosis), the molecular cascade underlying these benefits has been poorly defined. This study implemented a series of network medicine approaches and uncovered Pgc-1α as a mechanistic driver of the regulation of fibro-adipogenic progenitors (FAPs) by physical activity. Integrated in silico and in situ approaches to induce Pgc-1α overexpression promoted mitochondrial fatty acid oxidation and inhibited FAP adipogenesis. Together, the findings of the current study suggest a novel hypothesis that physical activity reduces myosteatosis via upregulation of Pgc-1α-mediated mitochondrial fatty acid oxidation and subsequent inhibition of FAP adipogenesis.

DOI： 10.1113/JP285349

Open Access

PubMed

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 Open Access

Yuki Sugiyama ,Kohei Uno ,Yusuke Matsui

PLoS Computational Biology 2023年1月

Types of anomalies in two-dimensional video-based gait analysis in uncontrolled environments Open Access

Yuki Sugiyama, Kohei Uno, Yusuke Matsui

PLOS Computational Biology 19 巻 ( 1 ) 頁： e1009989 - e1009989 2023年1月

担当区分：最終著者,　責任著者掲載種別：研究論文（学術雑誌）出版者・発行元：Public Library of Science (PLoS)

Two-dimensional video-based pose estimation is a technique that can be used to estimate human skeletal coordinates from video data alone. It is also being applied to gait analysis and in particularly, due to its simplicity of measurement, it has the potential to be applied to gait analysis of large populations. However, it is considered difficult to completely homogenize the environment and settings during the measurement of large populations. Therefore, it is necessary to appropriately deal with technical errors that are not related to the biological factors of interest. In this study, by analyzing a large cohort database, we have identified four major types of anomalies that occur during gait analysis using OpenPose in uncontrolled environments: anatomical, biomechanical, and physical anomalies and errors due to estimation. We have also developed a workflow for identifying and correcting these anomalies and confirmed that this workflow is reproducible through simulation experiments. Our results will help obtain a comprehensive understanding of the anomalies to be addressed during pre-processing for 2D video-based gait analysis of large populations.

DOI： 10.1371/journal.pcbi.1009989

Open Access

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