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Network modeling of...
Network modeling of the transcriptional effects of copy number aberrations in glioblastoma
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- Jörnsten, Rebecka, 1971 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper, matematisk statistik,Department of Mathematical Sciences, Mathematical Statistics,University of Gothenburg,Chalmers tekniska högskola,Chalmers University of Technology
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- Abenius, Tobias, 1979 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper, matematisk statistik,Department of Mathematical Sciences, Mathematical Statistics,University of Gothenburg,Chalmers tekniska högskola,Chalmers University of Technology
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- Kling, Teresia, 1985 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine,University of Gothenburg
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- Schmidt, Linnéa, 1985 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine,University of Gothenburg
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- Johansson, Erik (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine,University of Gothenburg
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- Nordling, Torbjorn E. M. (author)
- KTH,Reglerteknik
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- Nordlander, Bodil, 1976 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för cell- och molekylärbiologi, mikrobiologi,Department of Cell and Molecular Biology, Microbiology,University of Gothenburg
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- Sander, Chris (author)
- Memorial Sloan-Kettering Cancer Center
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- Gennemark, Peter, 1974 (author)
- Uppsala universitet,Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper,Department of Mathematical Sciences,University of Gothenburg,Chalmers tekniska högskola,Chalmers University of Technology,Analys och tillämpad matematik
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- Funa, Keiko, 1949 (author)
- Göteborgs universitet,University of Gothenburg
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- Nilsson, Björn (author)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine
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- Lindahl, Linda, 1972 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine,University of Gothenburg
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- Nelander, Sven, 1974 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine,University of Gothenburg
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(creator_code:org_t)
- 2011-04-26
- 2011
- English.
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In: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 7
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Abstract
Subject headings
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- DNA copy number aberrations (CNAs) are a hallmark of cancer genomes. However, little is known about how such changes affect global gene expression. We develop a modeling framework, EPoC (Endogenous Perturbation analysis of Cancer), to (1) detect disease-driving CNAs and their effect on target mRNA expression, and to (2) stratify cancer patients into long- and short-term survivors. Our method constructs causal network models of gene expression by combining genome-wide DNA- and RNA-level data. Prognostic scores are obtained from a singular value decomposition of the networks. By applying EPoC to glioblastoma data from The Cancer Genome Atlas consortium, we demonstrate that the resulting network models contain known disease-relevant hub genes, reveal interesting candidate hubs, and uncover predictors of patient survival. Targeted validations in four glioblastoma cell lines support selected predictions, and implicate the p53-interacting protein Necdin in suppressing glioblastoma cell growth. We conclude that large-scale network modeling of the effects of CNAs on gene expression may provide insights into the biology of human cancer. Free software in MATLAB and R is provided.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)
- NATURVETENSKAP -- Matematik -- Sannolikhetsteori och statistik (hsv//swe)
- NATURAL SCIENCES -- Mathematics -- Probability Theory and Statistics (hsv//eng)
- NATURVETENSKAP -- Biologi -- Annan biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Other Biological Topics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- Cell Line
- Tumor
- Chromosome Aberrations
- Databases
- Factual
- Gene Dosage
- Gene Expression Profiling
- Gene Expression Regulation
- Neoplastic
- Gene Regulatory Networks
- Genome
- Human
- Genome-Wide Association Study
- Glioblastoma
- genetics
- metabolism
- mortality
- pathology
- Humans
- Models
- Genetic
- Nerve Tissue Proteins
- genetics
- metabolism
- Nervous System Neoplasms
- genetics
- metabolism
- mortality
- pathology
- Nuclear Proteins
- genetics
- metabolism
- Prognosis
- Software
- Transcriptional Activation
- genetics
- Tumor Suppressor Protein p53
- genetics
- metabolism
- cancer biology
- cancer genomics
- glioblastoma
- metabolism
- Biochemistry
- Molecular biology
- MEDICINE
Publication and Content Type
- ref (subject category)
- art (subject category)
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Jörnsten, Rebeck ...
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Abenius, Tobias, ...
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Kling, Teresia, ...
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Schmidt, Linnéa, ...
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Johansson, Erik
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Nordling, Torbjo ...
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Nordlander, Bodi ...
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Sander, Chris
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Gennemark, Peter ...
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Funa, Keiko, 194 ...
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Nilsson, Björn
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Lindahl, Linda, ...
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Nelander, Sven, ...
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Molecular System ...
- By the university
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University of Gothenburg
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Lund University
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Chalmers University of Technology
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Royal Institute of Technology
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Uppsala University