title: Identification of multiple hypoxia signatures in neuroblastoma cell lines by l1-l2 regularization and data reduction.
abstract: Hypoxia is a condition of low oxygen tension occurring in the tumor and negatively correlated with the progression of the disease. We studied the gene expression profiles of nine neuroblastoma cell lines grown under hypoxic conditions to define gene signatures that characterize hypoxic neuroblastoma. The l(1)-l(2) regularization applied to the entire transcriptome identified a single signature of 11 probesets discriminating the hypoxic state. We demonstrate that new hypoxia signatures, with similar discriminatory power, can be generated by a prior knowledge-based filtering in which a much smaller number of probesets, characterizing hypoxia-related biochemical pathways, are analyzed. l(1)-l(2) regularization identified novel and robust hypoxia signatures within apoptosis, glycolysis, and oxidative phosphorylation Gene Ontology classes. We conclude that the filtering approach overcomes the noisy nature of the microarray data and allows generating robust signatures suitable for biomarker discovery and patients risk assessment in a fraction of computer time.
authors.affiliation: Laboratory of Molecular Biology, Gaslini Institute, 16147 Genoa, Italy. paolofardin@ospedale-gaslini.ge.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Fardin
authors.forename: Andrea
authors.initials: A
authors.lastname: Cornero
authors.forename: Annalisa
authors.initials: A
authors.lastname: Barla
authors.forename: Sofia
authors.initials: S
authors.lastname: Mosci
authors.forename: Massimo
authors.initials: M
authors.lastname: Acquaviva
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Rosasco
authors.forename: Claudio
authors.initials: C
authors.lastname: Gambini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Verri
authors.forename: Luigi
authors.initials: L
authors.lastname: Varesio
mesh_terms: D000465:Algorithms; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D015203:Reproducibility of Results