Processes in DNA damage response from a whole-cell multi-omics perspective
Summary: Technological advances have made it feasible to collect multi-condition multi-omic time courses of cellular response to perturbation, but the complexity of these datasets impedes discovery due to challenges in data management, analysis, visualization, and interpretation. Here, we report a w...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222016133 |
| _version_ | 1797990336294813696 |
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| author | James C. Pino Alexander L.R. Lubbock Leonard A. Harris Danielle B. Gutierrez Melissa A. Farrow Nicole Muszynski Tina Tsui Stacy D. Sherrod Jeremy L. Norris John A. McLean Richard M. Caprioli John P. Wikswo Carlos F. Lopez |
| author_facet | James C. Pino Alexander L.R. Lubbock Leonard A. Harris Danielle B. Gutierrez Melissa A. Farrow Nicole Muszynski Tina Tsui Stacy D. Sherrod Jeremy L. Norris John A. McLean Richard M. Caprioli John P. Wikswo Carlos F. Lopez |
| author_sort | James C. Pino |
| collection | DOAJ |
| description | Summary: Technological advances have made it feasible to collect multi-condition multi-omic time courses of cellular response to perturbation, but the complexity of these datasets impedes discovery due to challenges in data management, analysis, visualization, and interpretation. Here, we report a whole-cell mechanistic analysis of HL-60 cellular response to bendamustine. We integrate both enrichment and network analysis to show the progression of DNA damage and programmed cell death over time in molecular, pathway, and process-level detail using an interactive analysis framework for multi-omics data. Our framework, Mechanism of Action Generator Involving Network analysis (MAGINE), automates network construction and enrichment analysis across multiple samples and platforms, which can be integrated into our annotated gene-set network to combine the strengths of networks and ontology-driven analysis. Taken together, our work demonstrates how multi-omics integration can be used to explore signaling processes at various resolutions and demonstrates multi-pathway involvement beyond the canonical bendamustine mechanism. |
| first_indexed | 2024-04-11T08:33:44Z |
| format | Article |
| id | doaj.art-db35e3c9ebe3431c98e583179d280a79 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-11T08:33:44Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-db35e3c9ebe3431c98e583179d280a792022-12-22T04:34:23ZengElsevieriScience2589-00422022-11-012511105341Processes in DNA damage response from a whole-cell multi-omics perspectiveJames C. Pino0Alexander L.R. Lubbock1Leonard A. Harris2Danielle B. Gutierrez3Melissa A. Farrow4Nicole Muszynski5Tina Tsui6Stacy D. Sherrod7Jeremy L. Norris8John A. McLean9Richard M. Caprioli10John P. Wikswo11Carlos F. Lopez12Chemical and Physical Biology Graduate Program, Vanderbilt University, Nashville, TN, USA; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA; Pacific Northwest National Laboratory, Seattle, WA, USADepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Biomedical Engineering, University of Arkansas, Fayetteville, AR, USA; Interdisciplinary Graduate Program in Cell & Molecular Biology, University of Arkansas, Fayetteville, AR, USA; Cancer Biology Program, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USADepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USADepartment of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USADepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USADepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USAVanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Chemistry, Vanderbilt University, Nashville, TN, USA; Center for Innovative Technology (CIT), Vanderbilt University, Nashville, TN, USADepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA; Department of Chemistry, Vanderbilt University, Nashville, TN, USAVanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Chemistry, Vanderbilt University, Nashville, TN, USA; Center for Innovative Technology (CIT), Vanderbilt University, Nashville, TN, USADepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA; Department of Chemistry, Vanderbilt University, Nashville, TN, USA; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA; Department of Medicine, Vanderbilt University, Nashville, TN, USADepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA; Department of Physics and Astronomy, Vanderbilt University, Nashville, TN, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA; Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN, USADepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA; Pacific Northwest National Laboratory, Seattle, WA, USA; Corresponding authorSummary: Technological advances have made it feasible to collect multi-condition multi-omic time courses of cellular response to perturbation, but the complexity of these datasets impedes discovery due to challenges in data management, analysis, visualization, and interpretation. Here, we report a whole-cell mechanistic analysis of HL-60 cellular response to bendamustine. We integrate both enrichment and network analysis to show the progression of DNA damage and programmed cell death over time in molecular, pathway, and process-level detail using an interactive analysis framework for multi-omics data. Our framework, Mechanism of Action Generator Involving Network analysis (MAGINE), automates network construction and enrichment analysis across multiple samples and platforms, which can be integrated into our annotated gene-set network to combine the strengths of networks and ontology-driven analysis. Taken together, our work demonstrates how multi-omics integration can be used to explore signaling processes at various resolutions and demonstrates multi-pathway involvement beyond the canonical bendamustine mechanism.http://www.sciencedirect.com/science/article/pii/S2589004222016133BioinformaticsComplex system biologySystems biologyData processing in systems biology |
| spellingShingle | James C. Pino Alexander L.R. Lubbock Leonard A. Harris Danielle B. Gutierrez Melissa A. Farrow Nicole Muszynski Tina Tsui Stacy D. Sherrod Jeremy L. Norris John A. McLean Richard M. Caprioli John P. Wikswo Carlos F. Lopez Processes in DNA damage response from a whole-cell multi-omics perspective iScience Bioinformatics Complex system biology Systems biology Data processing in systems biology |
| title | Processes in DNA damage response from a whole-cell multi-omics perspective |
| title_full | Processes in DNA damage response from a whole-cell multi-omics perspective |
| title_fullStr | Processes in DNA damage response from a whole-cell multi-omics perspective |
| title_full_unstemmed | Processes in DNA damage response from a whole-cell multi-omics perspective |
| title_short | Processes in DNA damage response from a whole-cell multi-omics perspective |
| title_sort | processes in dna damage response from a whole cell multi omics perspective |
| topic | Bioinformatics Complex system biology Systems biology Data processing in systems biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222016133 |
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