title: Importance of rare gene copy number alterations for personalized tumor characterization and survival analysis.
abstract: It has proven exceedingly difficult to ascertain rare copy number alterations (CNAs) that may have strong effects in individual tumors. We show that a regulatory network inferred from gene expression and gene copy number data of 768 human cancer cell lines can be used to quantify the impact of patient-specific CNAs on survival signature genes. A focused analysis of tumors from six tissues reveals that rare patient-specific gene CNAs often have stronger effects on signature genes than frequent gene CNAs. Further comparison to a related network-based approach shows that the integration of indirectly acting gene CNAs significantly improves the survival analysis.
authors.affiliation: Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Institute for Medical Informatics and Biometry, Fetscherstr. 74, Dresden, 01307, Germany. michael.seifert@tu-dresden.de.|National Center for Tumor Diseases (NCT), Dresden, Germany. michael.seifert@tu-dresden.de.|Cellular Networks and Systems Biology, CECAD, University of Cologne, Joseph-Stelzmann-Str. 26, Cologne, 50931, Germany. michael.seifert@tu-dresden.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Seifert
authors.affiliation: Institute of Molecular Systems Biology, Auguste-Piccard-Hof 1, Zurich, 8093, Switzerland.
authors.forename: Betty
authors.initials: B
authors.lastname: Friedrich
authors.affiliation: Cellular Networks and Systems Biology, CECAD, University of Cologne, Joseph-Stelzmann-Str. 26, Cologne, 50931, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Beyer
mesh_terms: D019295:Computational Biology; D056915:DNA Copy Number Variations / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity / Q000235:genetics; D049490:Systems Biology; D014018:Tissue Distribution
keywords: Bioinformatics; Cancer genomics; Computational systems biology; Gene copy number mutations; Network biology; Network inference; Network propagation