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Systems Drug Discovery for Diffuse Large B Cell Lymphoma Based on Pathogenic Molecular Mechanism via Big Data Mining and Deep Learning Method

Diffuse large B cell lymphoma (DLBCL) is an aggressive heterogeneous disease. The most common subtypes of DLBCL include germinal center b-cell (GCB) type and activated b-cell (ABC) type. To learn more about the pathogenesis of two DLBCL subtypes (i.e., DLBCL ABC and DLBCL GCB), we firstly construct...

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Autores principales: Yeh, Shan-Ju, Yeh, Tsun-Yung, Chen, Bor-Sen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224183/
https://www.ncbi.nlm.nih.gov/pubmed/35743172
http://dx.doi.org/10.3390/ijms23126732
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author Yeh, Shan-Ju
Yeh, Tsun-Yung
Chen, Bor-Sen
author_facet Yeh, Shan-Ju
Yeh, Tsun-Yung
Chen, Bor-Sen
author_sort Yeh, Shan-Ju
collection PubMed
description Diffuse large B cell lymphoma (DLBCL) is an aggressive heterogeneous disease. The most common subtypes of DLBCL include germinal center b-cell (GCB) type and activated b-cell (ABC) type. To learn more about the pathogenesis of two DLBCL subtypes (i.e., DLBCL ABC and DLBCL GCB), we firstly construct a candidate genome-wide genetic and epigenetic network (GWGEN) by big database mining. With the help of two DLBCL subtypes’ genome-wide microarray data, we identify their real GWGENs via system identification and model order selection approaches. Afterword, the core GWGENs of two DLBCL subtypes could be extracted from real GWGENs by principal network projection (PNP) method. By comparing core signaling pathways and investigating pathogenic mechanisms, we are able to identify pathogenic biomarkers as drug targets for DLBCL ABC and DLBCL GCD, respectively. Furthermore, we do drug discovery considering drug-target interaction ability, drug regulation ability, and drug toxicity. Among them, a deep neural network (DNN)-based drug-target interaction (DTI) model is trained in advance to predict potential drug candidates holding higher probability to interact with identified biomarkers. Consequently, two drug combinations are proposed to alleviate DLBCL ABC and DLBCL GCB, respectively.
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spelling pubmed-92241832022-06-24 Systems Drug Discovery for Diffuse Large B Cell Lymphoma Based on Pathogenic Molecular Mechanism via Big Data Mining and Deep Learning Method Yeh, Shan-Ju Yeh, Tsun-Yung Chen, Bor-Sen Int J Mol Sci Article Diffuse large B cell lymphoma (DLBCL) is an aggressive heterogeneous disease. The most common subtypes of DLBCL include germinal center b-cell (GCB) type and activated b-cell (ABC) type. To learn more about the pathogenesis of two DLBCL subtypes (i.e., DLBCL ABC and DLBCL GCB), we firstly construct a candidate genome-wide genetic and epigenetic network (GWGEN) by big database mining. With the help of two DLBCL subtypes’ genome-wide microarray data, we identify their real GWGENs via system identification and model order selection approaches. Afterword, the core GWGENs of two DLBCL subtypes could be extracted from real GWGENs by principal network projection (PNP) method. By comparing core signaling pathways and investigating pathogenic mechanisms, we are able to identify pathogenic biomarkers as drug targets for DLBCL ABC and DLBCL GCD, respectively. Furthermore, we do drug discovery considering drug-target interaction ability, drug regulation ability, and drug toxicity. Among them, a deep neural network (DNN)-based drug-target interaction (DTI) model is trained in advance to predict potential drug candidates holding higher probability to interact with identified biomarkers. Consequently, two drug combinations are proposed to alleviate DLBCL ABC and DLBCL GCB, respectively. MDPI 2022-06-16 /pmc/articles/PMC9224183/ /pubmed/35743172 http://dx.doi.org/10.3390/ijms23126732 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yeh, Shan-Ju
Yeh, Tsun-Yung
Chen, Bor-Sen
Systems Drug Discovery for Diffuse Large B Cell Lymphoma Based on Pathogenic Molecular Mechanism via Big Data Mining and Deep Learning Method
title Systems Drug Discovery for Diffuse Large B Cell Lymphoma Based on Pathogenic Molecular Mechanism via Big Data Mining and Deep Learning Method
title_full Systems Drug Discovery for Diffuse Large B Cell Lymphoma Based on Pathogenic Molecular Mechanism via Big Data Mining and Deep Learning Method
title_fullStr Systems Drug Discovery for Diffuse Large B Cell Lymphoma Based on Pathogenic Molecular Mechanism via Big Data Mining and Deep Learning Method
title_full_unstemmed Systems Drug Discovery for Diffuse Large B Cell Lymphoma Based on Pathogenic Molecular Mechanism via Big Data Mining and Deep Learning Method
title_short Systems Drug Discovery for Diffuse Large B Cell Lymphoma Based on Pathogenic Molecular Mechanism via Big Data Mining and Deep Learning Method
title_sort systems drug discovery for diffuse large b cell lymphoma based on pathogenic molecular mechanism via big data mining and deep learning method
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224183/
https://www.ncbi.nlm.nih.gov/pubmed/35743172
http://dx.doi.org/10.3390/ijms23126732
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