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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/12/6732 |
| _version_ | 1797486443285708800 |
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| author | Shan-Ju Yeh Tsun-Yung Yeh Bor-Sen Chen |
| author_facet | Shan-Ju Yeh Tsun-Yung Yeh Bor-Sen Chen |
| author_sort | Shan-Ju Yeh |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T23:33:19Z |
| format | Article |
| id | doaj.art-951abfe7f3a04a6fa43f800b6063ed0e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:33:19Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-951abfe7f3a04a6fa43f800b6063ed0e2023-11-23T17:05:49ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012312673210.3390/ijms23126732Systems Drug Discovery for Diffuse Large B Cell Lymphoma Based on Pathogenic Molecular Mechanism via Big Data Mining and Deep Learning MethodShan-Ju Yeh0Tsun-Yung Yeh1Bor-Sen Chen2Laboratory of Automatic Control, Signal Processing and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, TaiwanLaboratory of Automatic Control, Signal Processing and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, TaiwanLaboratory of Automatic Control, Signal Processing and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, TaiwanDiffuse 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.https://www.mdpi.com/1422-0067/23/12/6732diffuse large B cell lymphoma (DLBCL)deep neural networkdrug discoverydrug combination |
| spellingShingle | Shan-Ju Yeh Tsun-Yung Yeh Bor-Sen Chen Systems Drug Discovery for Diffuse Large B Cell Lymphoma Based on Pathogenic Molecular Mechanism via Big Data Mining and Deep Learning Method International Journal of Molecular Sciences diffuse large B cell lymphoma (DLBCL) deep neural network drug discovery drug combination |
| 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 | diffuse large B cell lymphoma (DLBCL) deep neural network drug discovery drug combination |
| url | https://www.mdpi.com/1422-0067/23/12/6732 |
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