Generalized singular value decomposition of genomic profiles predicts gliobastoma survival

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Publication Type thesis
School or College College of Engineering
Department Bioengineering
Author Alpert, Benjamin O.
Title Generalized singular value decomposition of genomic profiles predicts gliobastoma survival
Date 2012-08
Description 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 is revealed 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 knowledge of 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 cycleregulated serine/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.
Type Text
Publisher University of Utah
Subject Gliobastoma survival; Genomic profiling; Generalized singular value decomposition
Subject LCSH Glioblastoma multiforme -- Genetic aspects; Genomics; Glioblastoma multiforme -- Prognosis
Dissertation Institution University of Utah
Dissertation Name Master of Science
Language eng
Rights Management Copyright © Benjamin O. Alpert 2012
Format Medium application/pdf
Format Extent 6,812,456 bytes
Identifier etd3/id/1799
Source Original in Marriott Library Special Collections, RC39.5 2012 .A46
ARK ark:/87278/s6ff4747
Setname ir_etd
Date Created 2012-08-06
Date Modified 2017-05-09
ID 195488
Reference URL