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  1. Article ; Online: Network-based prediction approach for cancer-specific driver missense mutations using a graph neural network

    Narumi Hatano / Mayumi Kamada / Ryosuke Kojima / Yasushi Okuno

    BMC Bioinformatics, Vol 24, Iss 1, Pp 1-

    2023  Volume 15

    Abstract: Abstract Background In cancer genomic medicine, finding driver mutations involved in cancer development and tumor growth is crucial. Machine-learning methods to predict driver missense mutations have been developed because variants are frequently ... ...

    Abstract Abstract Background In cancer genomic medicine, finding driver mutations involved in cancer development and tumor growth is crucial. Machine-learning methods to predict driver missense mutations have been developed because variants are frequently detected by genomic sequencing. However, even though the abnormalities in molecular networks are associated with cancer, many of these methods focus on individual variants and do not consider molecular networks. Here we propose a new network-based method, Net-DMPred, to predict driver missense mutations considering molecular networks. Net-DMPred consists of the graph part and the prediction part. In the graph part, molecular networks are learned by a graph neural network (GNN). The prediction part learns whether variants are driver variants using features of individual variants combined with the graph features learned in the graph part. Results Net-DMPred, which considers molecular networks, performed better than conventional methods. Furthermore, the prediction performance differed by the molecular network structure used in learning, suggesting that it is important to consider not only the local network related to cancer but also the large-scale network in living organisms. Conclusions We propose a network-based machine learning method, Net-DMPred, for predicting cancer driver missense mutations. Our method enables us to consider the entire graph architecture representing the molecular network because it uses GNN. Net-DMPred is expected to detect driver mutations from a lot of missense mutations that are not known to be associated with cancer.
    Keywords Driver mutation prediction ; Cancer missense mutation ; Graph neural network ; Molecular interaction ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Biology (General) ; QH301-705.5
    Subject code 006
    Language English
    Publishing date 2023-10-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Robust prognostic prediction model developed with integrated biological markers for acute myocardial infarction.

    Masahiro Nishi / Eiichiro Uchino / Yasushi Okuno / Satoaki Matoba

    PLoS ONE, Vol 17, Iss 11, p e

    2022  Volume 0277260

    Abstract: Commonly used prediction methods for acute myocardial infarction (AMI) were created before contemporary percutaneous coronary intervention was recognized as the primary therapy. Although several studies have used machine learning techniques for ... ...

    Abstract Commonly used prediction methods for acute myocardial infarction (AMI) were created before contemporary percutaneous coronary intervention was recognized as the primary therapy. Although several studies have used machine learning techniques for prognostic prediction of patients with AMI, its clinical application has not been achieved. Here, we developed an online application tool using a machine learning model to predict in-hospital mortality in patients with AMI. A total of 2,553 cases of ST-elevation AMI were assigned to 80% training subset for cross validation and 20% test subset for model performance evaluation. We implemented random forest classifier for the binary classification of in-hospital mortality. The selected best feature set consisted of ten clinical and biological markers including max creatine phosphokinase, hemoglobin, heart rate, creatinine, systolic blood pressure, blood sugar, age, Killip class, white blood cells, and c-reactive protein. Our model achieved high performance: the area under the curve of the receiver operating characteristic curve for the test subset, 0.95: sensitivity, 0.89: specificity, 0.91: precision, 0.43: accuracy, 0.91 respectively, which outperformed common scoring methods. The freely available application tool for prognostic prediction can contribute to risk triage and decision-making in patient-centered modern clinical practice for AMI.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Development and validation of ischemic heart disease and stroke prognostic models using large-scale real-world data from Japan

    Shigeto Yoshida / Shu Tanaka / Masafumi Okada / Takuya Ohki / Kazumasa Yamagishi / Yasushi Okuno

    Environmental Health and Preventive Medicine, Vol 28, Pp 16-

    2023  Volume 16

    Abstract: Background: Previous cardiovascular risk prediction models in Japan have utilized prospective cohort studies with concise data. As the health information including health check-up records and administrative claims becomes digitalized and publicly ... ...

    Abstract Background: Previous cardiovascular risk prediction models in Japan have utilized prospective cohort studies with concise data. As the health information including health check-up records and administrative claims becomes digitalized and publicly available, application of large datasets based on such real-world data can achieve prediction accuracy and support social implementation of cardiovascular disease risk prediction models in preventive and clinical practice. In this study, classical regression and machine learning methods were explored to develop ischemic heart disease (IHD) and stroke prognostic models using real-world data. Methods: IQVIA Japan Claims Database was searched to include 691,160 individuals (predominantly corporate employees and their families working in secondary and tertiary industries) with at least one annual health check-up record during the identification period (April 2013–December 2018). The primary outcome of the study was the first recorded IHD or stroke event. Predictors were annual health check-up records at the index year-month, comprising demographic characteristics, laboratory tests, and questionnaire features. Four prediction models (Cox, Elnet-Cox, XGBoost, and Ensemble) were assessed in the present study to develop a cardiovascular disease risk prediction model for Japan. Results: The analysis cohort consisted of 572,971 invididuals. All prediction models showed similarly good performance. The Harrell’s C-index was close to 0.9 for all IHD models, and above 0.7 for stroke models. In IHD models, age, sex, high-density lipoprotein, low-density lipoprotein, cholesterol, and systolic blood pressure had higher importance, while in stroke models systolic blood pressure and age had higher importance. Conclusion: Our study analyzed classical regression and machine learning algorithms to develop cardiovascular disease risk prediction models for IHD and stroke in Japan that can be applied to practical use in a large population with predictive accuracy.
    Keywords risk prediction model ; machine learning ; ischemic heart disease ; stroke ; real-world data ; Public aspects of medicine ; RA1-1270
    Subject code 310
    Language English
    Publishing date 2023-02-01T00:00:00Z
    Publisher Komiyama Printing Co. Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Mutual induced-fit mechanism drives binding between intrinsically disordered Bim and cryptic binding site of Bcl-xL

    Gert-Jan Bekker / Mitsugu Araki / Kanji Oshima / Yasushi Okuno / Narutoshi Kamiya

    Communications Biology, Vol 6, Iss 1, Pp 1-

    2023  Volume 11

    Abstract: Dynamic docking simulations reveal the interactions and conformational changes of the intrinsically disordered region of Bim and its cryptic binding site in Bcl-xL, a pro-survival protein involved in cancer progression. ...

    Abstract Dynamic docking simulations reveal the interactions and conformational changes of the intrinsically disordered region of Bim and its cryptic binding site in Bcl-xL, a pro-survival protein involved in cancer progression.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Characterizing eye-gaze positions of people with severe motor dysfunction

    Mari Okamoto / Ryosuke Kojima / Akihiko Ueda / Machiko Suzuki / Yasushi Okuno

    PLoS ONE, Vol 17, Iss 8, p e

    Novel scoring metrics using eye-tracking and video analysis.

    2022  Volume 0265623

    Abstract: Nonverbal communication with people who have physical disabilities is difficult. Eye-tracking technologies have recently been developed and applied to help people with physical disabilities in their communication. However, the eye-gaze patterns of people ...

    Abstract Nonverbal communication with people who have physical disabilities is difficult. Eye-tracking technologies have recently been developed and applied to help people with physical disabilities in their communication. However, the eye-gaze patterns of people with severe motor dysfunction (SMD) have not been analyzed in detail. To clarify characterization of people with SMD, we aimed to develop gaze position-based evaluation metrics and analyze detailed eye-gaze patterns of people with SMD. We developed two new scoring metrics: (1) saliency score based on three saliency maps-spectral residual (SR), fine grained (FG), and motion (Mo); and (2) the distance score, which represents to what extent people can chase an object in a video. The evaluation was performed on 102 participants, consisting of 35 subjects with profound intellectual and multiple disabilities (PIMD; SMD with IQ < 20), 19 with severe physical disabilities (SPD; SMD with IQ ≥ 20), and 48 healthy individuals. We observed that two saliency scores (SR and FG) and the distance score showed significant differences between the PIMD/SPD and healthy groups for the entire video, whereas Mo scores did not. Moreover, the distance score was analyzed separately for each scene, where scenes were categorized into three patterns-running, explanation, and hiding-according to the behavior of the moving objects. In the SPD and healthy groups, the explanation scenes accounted for the highest percentage of all scenes with the best distance score (63.6% and 61.9%, respectively), whereas in the PIMD group, the running scenes accounted for the highest percentage (54.5%). In conclusion, the new metrics were successful in quantitatively assessing the gaze responsiveness of people with SMD, which could not be assessed using a conventional metric, gaze-acquisition time. This study is expected to expand the possibilities of nonverbal communication using eye-tracking devices for people with SMD.
    Keywords Medicine ; R ; Science ; Q
    Subject code 360
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Exploring the mechanism of BK polyomavirus-associated nephropathy through consensus gene network approach.

    Noriaki Sato / Keita P Mori / Kaoru Sakai / Hitomi Miyata / Shinya Yamamoto / Takashi Kobayashi / Hironori Haga / Motoko Yanagita / Yasushi Okuno

    PLoS ONE, Vol 18, Iss 6, p e

    2023  Volume 0282534

    Abstract: BK polyomavirus-associated nephropathy occurs in kidney transplant recipients under immunosuppressive treatment. BK polyomavirus is implicated in cancer development and invasion, and case reports of renal cell carcinoma and urothelial carcinoma possibly ... ...

    Abstract BK polyomavirus-associated nephropathy occurs in kidney transplant recipients under immunosuppressive treatment. BK polyomavirus is implicated in cancer development and invasion, and case reports of renal cell carcinoma and urothelial carcinoma possibly associated with BK polyomavirus has been reported. Further, it has been suggested that the immune responses of KT-related diseases could play a role in the pathogenesis and progression of renal cell carcinoma. Thus, we thought to examine the relationship between BK polyomavirus-associated nephropathy and renal cell carcinoma in terms of gene expression. To identify the common and specific immune responses involved in kidney transplantation-related diseases with a specific focus on BK polyomavirus-associated nephropathy, we performed consensus weighted gene co-expression network analysis on gene profile datasets of renal biopsy samples from different institutions. After the identification of gene modules and validation of the obtained network by immunohistochemistry of the marker across kidney transplantation-related diseases, the relationship between prognosis of renal cell carcinoma and modules was assessed. We included the data from 248 patients and identified the 14 gene clusters across the datasets. We revealed that one cluster related to the translation regulating process and DNA damage response was specifically upregulated in BK polyomavirus-associated nephropathy. There was a significant association between the expression value of hub genes of the identified cluster including those related to cGAS-STING pathway and DNA damage response, and the prognosis of renal cell carcinoma. The study suggested the potential link between kidney transplantation-related diseases, especially specific transcriptomic signature of BK polyomavirus associated nephropathy and renal cell carcinoma.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Calculation of absolute binding free energies between the hERG channel and structurally diverse drugs

    Tatsuki Negami / Mitsugu Araki / Yasushi Okuno / Tohru Terada

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 12

    Abstract: Abstract The human ether-a-go-go-related gene (hERG) encodes a voltage-gated potassium channel that plays an essential role in the repolarization of action potentials in cardiac muscle. However, various drugs can block the ion current by binding to the ... ...

    Abstract Abstract The human ether-a-go-go-related gene (hERG) encodes a voltage-gated potassium channel that plays an essential role in the repolarization of action potentials in cardiac muscle. However, various drugs can block the ion current by binding to the hERG channel, resulting in potentially lethal cardiac arrhythmia. Accordingly, in silico studies are necessary to clarify the mechanisms of how these drugs bind to the hERG channel. Here, we used the experimental structure of the hERG channel, determined by cryo-electron microscopy, to perform docking simulations to predict the complex structures that occur between the hERG channel and structurally diverse drugs. The absolute binding free energies for the models were calculated using the MP-CAFEE method; calculated values were well correlated with experimental ones. By applying the regression equation obtained here, the affinity of a drug for the hERG channel can be accurately predicted from the calculated value of the absolute binding free energy.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2019-11-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Author Correction

    Shuntaro Chiba / Aki Tanabe / Makoto Nakakido / Yasushi Okuno / Kouhei Tsumoto / Masateru Ohta

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    Structure-based design and discovery of novel anti-tissue factor antibodies with cooperative double-point mutations, using interaction analysis

    2021  Volume 2

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Novel cancer subtyping method based on patient-specific gene regulatory network

    Mai Adachi Nakazawa / Yoshinori Tamada / Yoshihisa Tanaka / Marie Ikeguchi / Kako Higashihara / Yasushi Okuno

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 11

    Abstract: Abstract The identification of cancer subtypes is important for the understanding of tumor heterogeneity. In recent years, numerous computational methods have been proposed for this problem based on the multi-omics data of patients. It is widely accepted ...

    Abstract Abstract The identification of cancer subtypes is important for the understanding of tumor heterogeneity. In recent years, numerous computational methods have been proposed for this problem based on the multi-omics data of patients. It is widely accepted that different cancer subtypes are induced by different molecular regulatory networks. However, only a few incorporate the differences between their molecular systems into the identification processes. In this study, we present a novel method to identify cancer subtypes based on patient-specific molecular systems. Our method realizes this by quantifying patient-specific gene networks, which are estimated from their transcriptome data, and by clustering their quantified networks. Comprehensive analyses of The Cancer Genome Atlas (TCGA) datasets applied to our method confirmed that they were able to identify more clinically meaningful cancer subtypes than the existing subtypes and found that the identified subtypes comprised different molecular features. Our findings also show that the proposed method can identify the novel cancer subtypes even with single omics data, which cannot otherwise be captured by existing methods using multi-omics data.
    Keywords Medicine ; R ; Science ; Q
    Subject code 004
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Dynamic changes in gene-to-gene regulatory networks in response to SARS-CoV-2 infection

    Yoshihisa Tanaka / Kako Higashihara / Mai Adachi Nakazawa / Fumiyoshi Yamashita / Yoshinori Tamada / Yasushi Okuno

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 13

    Abstract: Abstract The current pandemic of SARS-CoV-2 has caused extensive damage to society. The characterization of SARS-CoV-2 profiles has been addressed by researchers globally with the aim of resolving this disruptive crisis. This investigation process is ... ...

    Abstract Abstract The current pandemic of SARS-CoV-2 has caused extensive damage to society. The characterization of SARS-CoV-2 profiles has been addressed by researchers globally with the aim of resolving this disruptive crisis. This investigation process is indispensable to understand how SARS-CoV-2 behaves in human host cells. However, little is known about the systematic molecular mechanisms involved in the effects of SARS-CoV-2 infection on human host cells. Here, we present gene-to-gene regulatory networks in response to SARS-CoV-2 using a Bayesian network. We examined the dynamic changes in the SARS-CoV-2-purturbated networks established by our proposed framework for gene network analysis, thus revealing that interferon signaling gradually switched to the subsequent inflammatory cytokine signaling cascades. Furthermore, we succeeded in capturing a COVID-19 patient-specific network in which transduction of these signals was concurrently induced. This enabled us to explore the local regulatory systems influenced by SARS-CoV-2 in host cells more precisely at an individual level. Our panel of network analyses has provided new insights into SARS-CoV-2 research from the perspective of cellular systems.
    Keywords Medicine ; R ; Science ; Q
    Subject code 303 ; 570
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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