title: Large-scale data integration framework provides a comprehensive view on glioblastoma multiforme.
abstract: BACKGROUND
  Coordinated efforts to collect large-scale data sets provide a basis for systems level understanding of complex diseases. In order to translate these fragmented and heterogeneous data sets into knowledge and medical benefits, advanced computational methods for data analysis, integration and visualization are needed.
  
  
  METHODS
  We introduce a novel data integration framework, Anduril, for translating fragmented large-scale data into testable predictions. The Anduril framework allows rapid integration of heterogeneous data with state-of-the-art computational methods and existing knowledge in bio-databases. Anduril automatically generates thorough summary reports and a website that shows the most relevant features of each gene at a glance, allows sorting of data based on different parameters, and provides direct links to more detailed data on genes, transcripts or genomic regions. Anduril is open-source; all methods and documentation are freely available.
  
  
  RESULTS
  We have integrated multidimensional molecular and clinical data from 338 subjects having glioblastoma multiforme, one of the deadliest and most poorly understood cancers, using Anduril. The central objective of our approach is to identify genetic loci and genes that have significant survival effect. Our results suggest several novel genetic alterations linked to glioblastoma multiforme progression and, more specifically, reveal Moesin as a novel glioblastoma multiforme-associated gene that has a strong survival effect and whose depletion in vitro significantly inhibited cell proliferation. All analysis results are available as a comprehensive website.
  
  
  CONCLUSIONS
  Our results demonstrate that integrated analysis and visualization of multidimensional and heterogeneous data by Anduril enables drawing conclusions on functional consequences of large-scale molecular data. Many of the identified genetic loci and genes having significant survival effect have not been reported earlier in the context of glioblastoma multiforme. Thus, in addition to generally applicable novel methodology, our results provide several glioblastoma multiforme candidate genes for further studies.Anduril is available at http://csbi.ltdk.helsinki.fi/anduril/The glioblastoma multiforme analysis results are available at http://csbi.ltdk.helsinki.fi/anduril/tcga-gbm/
authors.affiliation: Computational Systems Biology Laboratory, Institute of Biomedicine and Genome-Scale Biology Research Program, University of Helsinki, Haartmaninkatu 8, Helsinki, FIN-00014, Finland. kristian.ovaska@helsinki.fi.
authors.forename: Kristian
authors.initials: K
authors.lastname: Ovaska
authors.forename: Marko
authors.initials: M
authors.lastname: Laakso
authors.forename: Saija
authors.initials: S
authors.lastname: Haapa-Paananen
authors.forename: Riku
authors.initials: R
authors.lastname: Louhimo
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Viljami
authors.initials: V
authors.lastname: Aittomäki
authors.forename: Erkka
authors.initials: E
authors.lastname: Valo
authors.forename: Javier
authors.initials: J
authors.lastname: Núñez-Fontarnau
authors.forename: Ville
authors.initials: V
authors.lastname: Rantanen
authors.forename: Sirkku
authors.initials: S
authors.lastname: Karinen
authors.forename: Kari
authors.initials: K
authors.lastname: Nousiainen
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Lahesmaa-Korpinen
authors.forename: Minna
authors.initials: M
authors.lastname: Miettinen
authors.forename: Lilli
authors.initials: L
authors.lastname: Saarinen
authors.forename: Pekka
authors.initials: P
authors.lastname: Kohonen
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wu
authors.forename: Jukka
authors.initials: J
authors.lastname: Westermarck
authors.forename: Sampsa
authors.initials: S
authors.lastname: Hautaniemi
references.citation: Cancer Res. 2002 Nov 1;62(21):6240-5
references.pmid: 12414653
references.citation: Nat Genet. 2006 May;38(5):500-1
references.pmid: 16642009
references.citation: Bioinformatics. 1998;14(8):656-64
references.pmid: 9789091
references.citation: PLoS One. 2010 Feb 12;5(2):e8918
references.pmid: 20169195
references.citation: JAMA. 2009 Jul 15;302(3):261-75
references.pmid: 19602686
references.citation: Bioinformatics. 2004 Oct 12;20(15):2479-81
references.pmid: 15073010
references.citation: Genome Biol. 2004;5(10):R80
references.pmid: 15461798
references.citation: Biostatistics. 2004 Oct;5(4):557-72
references.pmid: 15475419
references.citation: J Cell Mol Med. 2009 Jan;13(1):39-53
references.pmid: 19175699
references.citation: Cancer Res. 2005 Jul 15;65(14):6029-33
references.pmid: 16024602
references.citation: Bioinformatics. 2010 Jan 15;26(2):161-7
references.pmid: 19933823
references.citation: Mol Cancer Res. 2007 Sep;5(9):881-90
references.pmid: 17855657
references.citation: Cancer Cell. 2010 Jan 19;17(1):98-110
references.pmid: 20129251
references.citation: Biostatistics. 2007 Apr;8(2):485-99
references.pmid: 17189563
references.citation: Bioinformatics. 2010 Jun 15;26(12):1488-92
references.pmid: 20413634
references.citation: Nucleic Acids Res. 2008 Jan;36(Database issue):D154-8
references.pmid: 17991681
references.citation: PLoS One. 2009 Nov 13;4(11):e7752
references.pmid: 19915670
references.citation: Bioinformatics. 2010 Jul 15;26(14):1802-3
references.pmid: 20507894
references.citation: Cancer Res. 2007 Oct 1;67(19):8994-9000
references.pmid: 17908999
references.citation: Bioinformatics. 2004 Nov 22;20(17):3045-54
references.pmid: 15201187
references.citation: Genes Dev. 2007 Nov 1;21(21):2683-710
references.pmid: 17974913
references.citation: Nat Methods. 2009 Jan;6(1):75-7
references.pmid: 19079255
references.citation: Neuropathology. 2010 Aug;30(4):392-400
references.pmid: 20051017
references.citation: Nature. 2010 Feb 18;463(7283):899-905
references.pmid: 20164920
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D690-7
references.pmid: 19033362
references.citation: Genome Biol. 2006;7(7):R66
references.pmid: 16869968
references.citation: Genes Dev. 2008 Feb 15;22(4):528-42
references.pmid: 18281465
references.citation: Nature. 2008 Oct 23;455(7216):1061-8
references.pmid: 18772890
references.citation: Nucleic Acids Res. 2008 Jan;36(Database issue):D480-4
references.pmid: 18077471
references.citation: J Neurooncol. 2009 May;92(3):297-306
references.pmid: 19357957