University of Utah
Alpert, Benjamin O.
Generalized singular value decomposition of genomic profiles predicts gliobastoma survival.
Degree: MS, Bioengineering, 2012, University of Utah
Despite recent large-scale proling efforts, the best prognostic predictor of glioblastoma multiforme (GBM) remains the patient's age at diagnosis. We describe a global pattern of tumor-exclusive co-occurring copy-number alterations (CNAs) that is correlated, possibly coordinated with GBM patients' survival and response to chemotherapy. The pattern isrevealed by GSVD comparison of patient-matched but probe-independent GBM and normal aCGH datasets from The Cancer Genome Atlas (TCGA). We find that, first, the GSVD, formulated as a framework for comparatively modeling two composite datasets, removes from the pattern copy-number variations (CNVs) that occur in the normal human genome (e.g., female-specic X chromosome amplication) and experimental variations (e.g., in tissue batch, genomic center, hybridization date and scanner), without a-priori knowledgeof these variations. Second, the pattern includes most known GBM-associated changes in chromosome numbers and focal CNAs, as well as several previously unreported CNAs in >3% of the patients. These include the biochemically putative drug target, cell cycleregulatedserine/threonine kinase-encoding TLK2, the cyclin E1-encoding CCNE1, and the Rb-binding histone demethylase-encoding KDM5A. Third, the pattern provides a better prognostic predictor than the chromosome numbers or any one focal CNA that it identifies, suggesting that the GBM survival phenotype is an outcome of its global genotype. The pattern is independent of age, and combined with age, makes a better predictor than age alone. GSVD comparison of matched proles of a larger set of TCGA patients, inclusive of the initial set, confirms the global pattern. GSVD classication of the GBM profiles of an independent set of patients validates the prognostic contribution of the pattern.
Subjects/Keywords: Gliobastoma survival; Genomic profiling; Generalized singular value decomposition
to Zotero / EndNote / Reference
APA (6th Edition):
Alpert, B. O. (2012). Generalized singular value decomposition of genomic profiles predicts gliobastoma survival. (Masters Thesis). University of Utah. Retrieved from http://content.lib.utah.edu/cdm/singleitem/collection/etd3/id/1799/rec/1102
Chicago Manual of Style (16th Edition):
Alpert, Benjamin O. “Generalized singular value decomposition of genomic profiles predicts gliobastoma survival.” 2012. Masters Thesis, University of Utah. Accessed July 02, 2020.
MLA Handbook (7th Edition):
Alpert, Benjamin O. “Generalized singular value decomposition of genomic profiles predicts gliobastoma survival.” 2012. Web. 02 Jul 2020.
Alpert BO. Generalized singular value decomposition of genomic profiles predicts gliobastoma survival. [Internet] [Masters thesis]. University of Utah; 2012. [cited 2020 Jul 02].
Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd3/id/1799/rec/1102.
Council of Science Editors:
Alpert BO. Generalized singular value decomposition of genomic profiles predicts gliobastoma survival. [Masters Thesis]. University of Utah; 2012. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd3/id/1799/rec/1102