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Predicting potential lncRNA biomarkers for lung cancer and neuroblastoma based on an ensemble of a deep neural network and LightGBM
Introduction: Lung cancer is one of the most frequent neoplasms worldwide with approximately 2.2 million new cases and 1.8 million deaths each year. The expression levels of programmed death ligand-1 (PDL1) demonstrate a complex association with lung cancer. Neuroblastoma is a high-risk malignant tu...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10466784/ https://www.ncbi.nlm.nih.gov/pubmed/37655066 http://dx.doi.org/10.3389/fgene.2023.1238095 |
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author | Su, Zhenguo Lu, Huihui Wu, Yan Li, Zejun Duan, Lian |
author_facet | Su, Zhenguo Lu, Huihui Wu, Yan Li, Zejun Duan, Lian |
author_sort | Su, Zhenguo |
collection | PubMed |
description | Introduction: Lung cancer is one of the most frequent neoplasms worldwide with approximately 2.2 million new cases and 1.8 million deaths each year. The expression levels of programmed death ligand-1 (PDL1) demonstrate a complex association with lung cancer. Neuroblastoma is a high-risk malignant tumor and is mainly involved in childhood patients. Identification of new biomarkers for these two diseases can significantly promote their diagnosis and therapy. However, in vivo experiments to discover potential biomarkers are costly and laborious. Consequently, artificial intelligence technologies, especially machine learning methods, provide a powerful avenue to find new biomarkers for various diseases. Methods: We developed a machine learning-based method named LDAenDL to detect potential long noncoding RNA (lncRNA) biomarkers for lung cancer and neuroblastoma using an ensemble of a deep neural network and LightGBM. LDAenDL first computes the Gaussian kernel similarity and functional similarity of lncRNAs and the Gaussian kernel similarity and semantic similarity of diseases to obtain their similar networks. Next, LDAenDL combines a graph convolutional network, graph attention network, and convolutional neural network to learn the biological features of the lncRNAs and diseases based on their similarity networks. Third, these features are concatenated and fed to an ensemble model composed of a deep neural network and LightGBM to find new lncRNA–disease associations (LDAs). Finally, the proposed LDAenDL method is applied to identify possible lncRNA biomarkers associated with lung cancer and neuroblastoma. Results: The experimental results show that LDAenDL computed the best AUCs of 0.8701, 107 0.8953, and 0.9110 under cross-validation on lncRNAs, diseases, and lncRNA‐disease pairs on Dataset 1, respectively, and 0.9490, 0.9157, and 0.9708 on Dataset 2, respectively. Furthermore, AUPRs of 0.8903, 0.9061, and 0.9166 under three cross‐validations were obtained on Dataset 1, and 0.9582, 0.9122, and 0.9743 on Dataset 2. The results demonstrate that LDAenDL significantly outperformed the other four classical LDA prediction methods (i.e., SDLDA, LDNFSGB, IPCAF, and LDASR). Case studies demonstrate that CCDC26 and IFNG-AS1 may be new biomarkers of lung cancer, SNHG3 may associate with PDL1 for lung cancer, and HOTAIR and BDNF-AS may be potential biomarkers of neuroblastoma. Conclusion: We hope that the proposed LDAenDL method can help the development of targeted therapies for these two diseases. |
format | Online Article Text |
id | pubmed-10466784 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-104667842023-08-31 Predicting potential lncRNA biomarkers for lung cancer and neuroblastoma based on an ensemble of a deep neural network and LightGBM Su, Zhenguo Lu, Huihui Wu, Yan Li, Zejun Duan, Lian Front Genet Genetics Introduction: Lung cancer is one of the most frequent neoplasms worldwide with approximately 2.2 million new cases and 1.8 million deaths each year. The expression levels of programmed death ligand-1 (PDL1) demonstrate a complex association with lung cancer. Neuroblastoma is a high-risk malignant tumor and is mainly involved in childhood patients. Identification of new biomarkers for these two diseases can significantly promote their diagnosis and therapy. However, in vivo experiments to discover potential biomarkers are costly and laborious. Consequently, artificial intelligence technologies, especially machine learning methods, provide a powerful avenue to find new biomarkers for various diseases. Methods: We developed a machine learning-based method named LDAenDL to detect potential long noncoding RNA (lncRNA) biomarkers for lung cancer and neuroblastoma using an ensemble of a deep neural network and LightGBM. LDAenDL first computes the Gaussian kernel similarity and functional similarity of lncRNAs and the Gaussian kernel similarity and semantic similarity of diseases to obtain their similar networks. Next, LDAenDL combines a graph convolutional network, graph attention network, and convolutional neural network to learn the biological features of the lncRNAs and diseases based on their similarity networks. Third, these features are concatenated and fed to an ensemble model composed of a deep neural network and LightGBM to find new lncRNA–disease associations (LDAs). Finally, the proposed LDAenDL method is applied to identify possible lncRNA biomarkers associated with lung cancer and neuroblastoma. Results: The experimental results show that LDAenDL computed the best AUCs of 0.8701, 107 0.8953, and 0.9110 under cross-validation on lncRNAs, diseases, and lncRNA‐disease pairs on Dataset 1, respectively, and 0.9490, 0.9157, and 0.9708 on Dataset 2, respectively. Furthermore, AUPRs of 0.8903, 0.9061, and 0.9166 under three cross‐validations were obtained on Dataset 1, and 0.9582, 0.9122, and 0.9743 on Dataset 2. The results demonstrate that LDAenDL significantly outperformed the other four classical LDA prediction methods (i.e., SDLDA, LDNFSGB, IPCAF, and LDASR). Case studies demonstrate that CCDC26 and IFNG-AS1 may be new biomarkers of lung cancer, SNHG3 may associate with PDL1 for lung cancer, and HOTAIR and BDNF-AS may be potential biomarkers of neuroblastoma. Conclusion: We hope that the proposed LDAenDL method can help the development of targeted therapies for these two diseases. Frontiers Media S.A. 2023-08-16 /pmc/articles/PMC10466784/ /pubmed/37655066 http://dx.doi.org/10.3389/fgene.2023.1238095 Text en Copyright © 2023 Su, Lu, Wu, Li and Duan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Su, Zhenguo Lu, Huihui Wu, Yan Li, Zejun Duan, Lian Predicting potential lncRNA biomarkers for lung cancer and neuroblastoma based on an ensemble of a deep neural network and LightGBM |
title | Predicting potential lncRNA biomarkers for lung cancer and neuroblastoma based on an ensemble of a deep neural network and LightGBM |
title_full | Predicting potential lncRNA biomarkers for lung cancer and neuroblastoma based on an ensemble of a deep neural network and LightGBM |
title_fullStr | Predicting potential lncRNA biomarkers for lung cancer and neuroblastoma based on an ensemble of a deep neural network and LightGBM |
title_full_unstemmed | Predicting potential lncRNA biomarkers for lung cancer and neuroblastoma based on an ensemble of a deep neural network and LightGBM |
title_short | Predicting potential lncRNA biomarkers for lung cancer and neuroblastoma based on an ensemble of a deep neural network and LightGBM |
title_sort | predicting potential lncrna biomarkers for lung cancer and neuroblastoma based on an ensemble of a deep neural network and lightgbm |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10466784/ https://www.ncbi.nlm.nih.gov/pubmed/37655066 http://dx.doi.org/10.3389/fgene.2023.1238095 |
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