title: Pathway-based personalized analysis of cancer.
abstract: We introduce Pathifier, an algorithm that infers pathway deregulation scores for each tumor sample on the basis of expression data. This score is determined, in a context-specific manner, for every particular dataset and type of cancer that is being investigated. The algorithm transforms gene-level information into pathway-level information, generating a compact and biologically relevant representation of each sample. We demonstrate the algorithm's performance on three colorectal cancer datasets and two glioblastoma multiforme datasets and show that our multipathway-based representation is reproducible, preserves much of the original information, and allows inference of complex biologically significant information. We discovered several pathways that were significantly associated with survival of glioblastoma patients and two whose scores are predictive of survival in colorectal cancer: CXCR3-mediated signaling and oxidative phosphorylation. We also identified a subclass of proneural and neural glioblastoma with significantly better survival, and an EGF receptor-deregulated subclass of colon cancers.
authors.affiliation: Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Yotam
authors.initials: Y
authors.lastname: Drier
authors.forename: Michal
authors.initials: M
authors.lastname: Sheffer
authors.forename: Eytan
authors.initials: E
authors.lastname: Domany
mesh_terms: D000465:Algorithms; D015179:Colorectal Neoplasms / Q000235:genetics; D019295:Computational Biology / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D023281:Genomics / Q000379:methods; D005909:Glioblastoma / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D010085:Oxidative Phosphorylation; D057285:Precision Medicine / Q000379:methods*; D054367:Receptors, CXCR3 / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics*; D012984:Software; D049490:Systems Biology / Q000379:methods
chemical_list: C515187:CXCR3 protein, human; D054367:Receptors, CXCR3
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