Identification of multiple hypoxia signatures in neuroblastoma cell lines by l1-l2 regularization and data reduction

Paolo Fardin, Andrea Cornero, Annalisa Barla, Sofia Mosci, Massimo Acquaviva, Lorenzo Rosasco, Claudio Gambini, Alessandro Verri, Luigi Varesio

Research output: Contribution to journalArticlepeer-review


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 l1-l2 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. l1-l2 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.

Original languageEnglish
Article number878709
JournalJournal of Biomedicine and Biotechnology
Publication statusPublished - 2010

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Genetics
  • Molecular Biology
  • Health, Toxicology and Mutagenesis
  • Medicine(all)


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