دورية أكاديمية
Phenotypic deconvolution in heterogeneous cancer cell populations using drug-screening data.
| العنوان: | Phenotypic deconvolution in heterogeneous cancer cell populations using drug-screening data. |
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| المؤلفون: | Köhn-Luque A; Oslo Centre for Biostatistics and Epidemiology, Faculty of Medicine, University of Oslo, 0372 Oslo, Norway., Myklebust EM; Oslo Centre for Biostatistics and Epidemiology, Faculty of Medicine, University of Oslo, 0372 Oslo, Norway., Tadele DS; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, 0379 Oslo, Norway.; Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0318 Oslo, Norway.; Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, OH 44131, USA., Giliberto M; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, 0310 Oslo, Norway.; KG Jebsen Center for B-Cell Malignancies, Institute for Clinical Medicine, University of Oslo, 0450 Oslo, Norway., Schmiester L; Oslo Centre for Biostatistics and Epidemiology, Faculty of Medicine, University of Oslo, 0372 Oslo, Norway., Noory J; Institute for Mathematics and its Applications, School of Mathematics, University of Minnesota, Minneapolis, MN 55455, USA., Harivel E; Oslo Centre for Biostatistics and Epidemiology, Faculty of Medicine, University of Oslo, 0372 Oslo, Norway.; ENSTA, Institut Polytechnique de Paris, Palaiseau, 91120 Paris, France., Arsenteva P; Oslo Centre for Biostatistics and Epidemiology, Faculty of Medicine, University of Oslo, 0372 Oslo, Norway.; Institut de Matématiques de Bourgogne, Universite de Bourgogne, Dijon Cedex, 21078 Dijon, France., Mumenthaler SM; Lawrence J. Ellison Institute for Transformative Medicine, Los Angeles, CA 90064, USA.; Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA.; Department of Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA., Schjesvold F; KG Jebsen Center for B-Cell Malignancies, Institute for Clinical Medicine, University of Oslo, 0450 Oslo, Norway.; Oslo Myeloma Center, Department of Hematology, Oslo University Hospital, 0450 Oslo, Norway., Taskén K; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, 0310 Oslo, Norway.; KG Jebsen Center for B-Cell Malignancies, Institute for Clinical Medicine, University of Oslo, 0450 Oslo, Norway., Enserink JM; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, 0379 Oslo, Norway.; Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0318 Oslo, Norway.; Section for Biochemistry and Molecular Biology, Faculty of Mathematics and Natural Sciences, University of Oslo, 0037 Oslo, Norway., Leder K; College of Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA., Frigessi A; Oslo Centre for Biostatistics and Epidemiology, Faculty of Medicine, University of Oslo, 0372 Oslo, Norway.; Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, 0372 Oslo, Norway., Foo J; Institute for Mathematics and its Applications, School of Mathematics, University of Minnesota, Minneapolis, MN 55455, USA. |
| المصدر: | Cell reports methods [Cell Rep Methods] 2023 Mar 06; Vol. 3 (3), pp. 100417. Date of Electronic Publication: 2023 Mar 06 (Print Publication: 2023). |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc Country of Publication: United States NLM ID: 9918227360606676 Publication Model: eCollection Cited Medium: Internet ISSN: 2667-2375 (Electronic) Linking ISSN: 26672375 NLM ISO Abbreviation: Cell Rep Methods |
| أسماء مطبوعة: | Original Publication: [New York] : Elsevier Inc., [2021]- |
| مواضيع طبية MeSH: | Neoplasms*/drug therapy , Antineoplastic Agents*/pharmacology, Humans ; Early Detection of Cancer ; Cell Line ; Genomics |
| مستخلص: | Tumor heterogeneity is an important driver of treatment failure in cancer since therapies often select for drug-tolerant or drug-resistant cellular subpopulations that drive tumor growth and recurrence. Profiling the drug-response heterogeneity of tumor samples using traditional genomic deconvolution methods has yielded limited results, due in part to the imperfect mapping between genomic variation and functional characteristics. Here, we leverage mechanistic population modeling to develop a statistical framework for profiling phenotypic heterogeneity from standard drug-screen data on bulk tumor samples. This method, called PhenoPop, reliably identifies tumor subpopulations exhibiting differential drug responses and estimates their drug sensitivities and frequencies within the bulk population. We apply PhenoPop to synthetically generated cell populations, mixed cell-line experiments, and multiple myeloma patient samples and demonstrate how it can provide individualized predictions of tumor growth under candidate therapies. This methodology can also be applied to deconvolution problems in a variety of biological settings beyond cancer drug response. Competing Interests: The authors declare no competing interests. (© 2023 The Author(s).) |
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| فهرسة مساهمة: | Keywords: deconvolution; drug resistance; drug screening; mechanistic modeling; multiple myeloma; tumor heterogeneity; tumor profiling |
| المشرفين على المادة: | 0 (Antineoplastic Agents) |
| تواريخ الأحداث: | Date Created: 20230414 Date Completed: 20231020 Latest Revision: 20231020 |
| رمز التحديث: | 20231020 |
| مُعرف محوري في PubMed: | PMC10088094 |
| DOI: | 10.1016/j.crmeth.2023.100417 |
| PMID: | 37056380 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2667-2375 |
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| DOI: | 10.1016/j.crmeth.2023.100417 |