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  • 1
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 13 ( 2022-9-2)
    Abstract: Background: Linking genotypic changes to phenotypic traits based on machine learning methods has various challenges. In this study, we developed a workflow based on bioinformatics and machine learning methods using transcriptomic data for sepsis obtained at the first clinical presentation for predicting the risk of sepsis. By combining bioinformatics with machine learning methods, we have attempted to overcome current challenges in predicting disease risk using transcriptomic data. Methods: High-throughput sequencing transcriptomic data processing and gene annotation were performed using R software. Machine learning models were constructed, and model performance was evaluated by machine learning methods in Python. The models were visualized and interpreted using the Shapley Additive explanation (SHAP) method. Results: Based on the preset parameters and using recursive feature elimination implemented via machine learning, the top 10 optimal genes were screened for the establishment of the machine learning models. In a comparison of model performance, CatBoost was selected as the optimal model. We explored the significance of each gene in the model and the interaction between each gene through SHAP analysis. Conclusion: The combination of CatBoost and SHAP may serve as the best-performing machine learning model for predicting transcriptomic and sepsis risks. The workflow outlined may provide a new approach and direction in exploring the mechanisms associated with genes and sepsis risk.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606823-0
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  • 2
    In: BMC Pulmonary Medicine, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2022-09-02)
    Abstract: Currently, the rate of morbidity and mortality in acute respiratory distress syndrome (ARDS) remains high. One of the potential reasons for the poor and ineffective therapies is the lack of early and credible indicator of risk prediction that would help specific treatment of severely affected ARDS patients. Nevertheless, assessment of the clinical outcomes with transcriptomics of ARDS by alveolar macrophage has not been performed. Methods The expression data GSE116560 was obtained from the Gene Expression Omnibus databases (GEO) in NCBI. This dataset consists of 68 BAL samples from 35 subjects that were collected within 48 h of ARDS. Differentially expressed genes (DEGs) of different outcomes were analyzed using R software. The top 10 DEGs that were up- or down-regulated were analyzed using receiver operating characteristic (ROC) analysis. Kaplan–Meier survival analysis within two categories according to cut-off and the value of prediction of the clinical outcomes via DEGs was verified. GO enrichment, KEGG pathway analysis, and protein–protein interaction were also used for functional annotation of key genes. Results 24,526 genes were obtained, including 235 up-regulated and 292 down-regulated DEGs. The gene ADORA3 was chosen as the most obvious value to predict the outcome according to the ROC and survival analysis. For functional annotation, ADORA3 was significantly augmented in sphingolipid signaling pathway, cGMP-PKG signaling pathway, and neuroactive ligand-receptor interaction. Four genes (ADORA3, GNB1, NTS, and RHO), with 4 nodes and 6 edges, had the highest score in these clusters in the protein–protein interaction network. Conclusions Our results show that the prognostic prediction of early biomarkers of transcriptomics as identified in alveolar macrophage in ARDS can be extended for mechanically ventilated critically ill patients. In the long term, generalizing the concept of biomarkers of transcriptomics in alveolar macrophage could add to improving precision-based strategies in the ICU patients and may also lead to identifying improved strategy for critically ill patients.
    Type of Medium: Online Resource
    ISSN: 1471-2466
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2059871-3
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  • 3
    In: BMC Infectious Diseases, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2023-02-06)
    Abstract: Sepsis has the characteristics of high incidence, high mortality of ICU patients. Early assessment of disease severity and risk stratification of death in patients with sepsis, and further targeted intervention are very important. The purpose of this study was to develop machine learning models based on sequential organ failure assessment (SOFA) components to early predict in-hospital mortality in ICU patients with sepsis and evaluate model performance. Methods Patients admitted to ICU with sepsis diagnosis were extracted from MIMIC-IV database for retrospective analysis, and were randomly divided into training set and test set in accordance with 2:1. Six variables were included in this study, all of which were from the scores of 6 organ systems in SOFA score. The machine learning model was trained in the training set and evaluated in the validation set. Six machine learning methods including linear regression analysis, least absolute shrinkage and selection operator (LASSO), Logistic regression analysis (LR), Gaussian Naive Bayes (GNB) and support vector machines (SVM) were used to construct the death risk prediction models, and the accuracy, area under the receiver operating characteristic curve (AUROC), Decision Curve Analysis (DCA) and K-fold cross-validation were used to evaluate the prediction performance of developed models. Result A total of 23,889 patients with sepsis were enrolled, of whom 3659 died in hospital. Three feature variables including renal system score, central nervous system score and cardio vascular system score were used to establish prediction models. The accuracy of the LR, GNB, SVM were 0.851, 0.844 and 0.862, respectively, which were better than linear regression analysis (0.123) and LASSO (0.130). The AUROCs of LR, GNB and SVM were 0.76, 0.76 and 0.67, respectively. K-fold cross validation showed that the average AUROCs of LR, GNB and SVM were 0.757 ± 0.005, 0.762 ± 0.006, 0.630 ± 0.013, respectively. For the probability threshold of 5–50%, LY and GNB models both showed positive net benefits. Conclusion The two machine learning-based models (LR and GNB models) based on SOFA components can be used to predict in-hospital mortality of septic patients admitted to ICU.
    Type of Medium: Online Resource
    ISSN: 1471-2334
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2041550-3
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  • 4
    In: Hepatology Communications, Ovid Technologies (Wolters Kluwer Health), Vol. 7, No. 8 ( 2023-08-3)
    Abstract: The role of thioredoxin-interacting protein (TXNIP) in lipopolysaccharide-induced liver injury in mice has been reported, but the underlying mechanisms are poorly understood. Methods: We overexpressed deubiquitinase in cells overexpressing TXNIP and then detected the level of TXNIP to screen out the deubiquitinase regulating TXNIP; the interaction between TXNIP and deubiquitinase was verified by coimmunoprecipitation. After knockdown of a deubiquitinase and overexpression of TXNIP in Huh7 and HepG2 cells, lipopolysaccharide was used to establish a cellular inflammatory model to explore the role of deubiquitinase and TXNIP in hepatocyte inflammation. Results: In this study, we discovered that ubiquitin-specific protease 5 (USP5) interacts with TXNIP and stabilizes it through deubiquitylation in Huh-7 and HepG2 cells after treatment with lipopolysaccharide. In lipopolysaccharide-treated Huh-7 and HepG2 cells, USP5 knockdown increased cell viability, reduced apoptosis, and decreased the expression of inflammatory factors, including NLRP3, IL-1β, IL-18, ASC, and procaspase-1. Overexpression of TXNIP reversed the phenotype induced by knockdown USP5. Conclusions: In summary, USP5 promotes lipopolysaccharide-induced apoptosis and inflammatory response by stabilizing the TXNIP protein.
    Type of Medium: Online Resource
    ISSN: 2471-254X
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2881134-3
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