دورية أكاديمية
Unveiling the Dynamics behind Glioblastoma Multiforme Single-Cell Data Heterogeneity.
العنوان: | Unveiling the Dynamics behind Glioblastoma Multiforme Single-Cell Data Heterogeneity. |
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المؤلفون: | Junior MGV; Graduate Program in Computational and Systems Biology, Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil., Côrtes AMA; Department of Applied Mathematics, Institute of Mathematics, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-909, Brazil.; Systems Engineering and Computer Science Program, Coordination of Postgraduate Programs in Engineering (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-972, Brazil., Carneiro FRG; Center of Technological Development in Health (CDTS), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-361, Brazil.; Laboratório Interdisciplinar de Pesquisas Médicas, Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil.; Program of Immunology and Tumor Biology, Brazilian National Cancer Institute (INCA), Rio de Janeiro 20231-050, Brazil., Carels N; Laboratory of Biological System Modeling, Center of Technological Development in Health (CDTS), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-361, Brazil., Silva FABD; Scientific Computing Program, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21041-222, Brazil. |
المصدر: | International journal of molecular sciences [Int J Mol Sci] 2024 Apr 30; Vol. 25 (9). Date of Electronic Publication: 2024 Apr 30. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI, [2000- |
مواضيع طبية MeSH: | Glioblastoma*/genetics , Glioblastoma*/pathology , Glioblastoma*/metabolism , Single-Cell Analysis*/methods , Brain Neoplasms*/genetics , Brain Neoplasms*/pathology , Brain Neoplasms*/metabolism, Humans ; Gene Expression Regulation, Neoplastic ; Genetic Heterogeneity ; Gene Expression Profiling/methods ; Genomic Instability ; Sequence Analysis, RNA/methods ; Cluster Analysis |
مستخلص: | Glioblastoma Multiforme is a brain tumor distinguished by its aggressiveness. We suggested that this aggressiveness leads single-cell RNA-sequence data (scRNA-seq) to span a representative portion of the cancer attractors domain. This conjecture allowed us to interpret the scRNA-seq heterogeneity as reflecting a representative trajectory within the attractor's domain. We considered factors such as genomic instability to characterize the cancer dynamics through stochastic fixed points. The fixed points were derived from centroids obtained through various clustering methods to verify our method sensitivity. This methodological foundation is based upon sample and time average equivalence, assigning an interpretative value to the data cluster centroids and supporting parameters estimation. We used stochastic simulations to reproduce the dynamics, and our results showed an alignment between experimental and simulated dataset centroids. We also computed the Waddington landscape, which provided a visual framework for validating the centroids and standard deviations as characterizations of cancer attractors. Additionally, we examined the stability and transitions between attractors and revealed a potential interplay between subtypes. These transitions might be related to cancer recurrence and progression, connecting the molecular mechanisms of cancer heterogeneity with statistical properties of gene expression dynamics. Our work advances the modeling of gene expression dynamics and paves the way for personalized therapeutic interventions. |
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معلومات مُعتمدة: | 88887.597339/2021-00 Coordenação de Aperfeicoamento de Pessoal de Nível Superior |
فهرسة مساهمة: | Keywords: Glioblastoma Multiforme; cancer attractors; epigenetic landscape; gene regulatory network dynamics; heterogeneity; parameter sets estimation; single-cell RNA sequencing |
تواريخ الأحداث: | Date Created: 20240511 Date Completed: 20240511 Latest Revision: 20240513 |
رمز التحديث: | 20240513 |
مُعرف محوري في PubMed: | PMC11084314 |
DOI: | 10.3390/ijms25094894 |
PMID: | 38732140 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1422-0067 |
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DOI: | 10.3390/ijms25094894 |