title: Identification of ovarian cancer associated genes using an integrated approach in a Boolean framework.
abstract: BACKGROUND
  Cancer is a complex disease where molecular mechanism remains elusive. A systems approach is needed to integrate diverse biological information for the prognosis and therapy risk assessment using mechanistic approach to understand gene interactions in pathways and networks and functional attributes to unravel the biological behaviour of tumors.
  
  
  RESULTS
  We weighted the functional attributes based on various functional properties observed between cancerous and non-cancerous genes reported from literature. This weighing schema was then encoded in a Boolean logic framework to rank differentially expressed genes. We have identified 17 genes to be differentially expressed from a total of 11,173 genes, where ten genes are reported to be down-regulated via epigenetic inactivation and seven genes are up-regulated. Here, we report that the overexpressed genes IRAK1, CHEK1 and BUB1 may play an important role in ovarian cancer. We also show that these 17 genes can be used to form an ovarian cancer signature, to distinguish normal from ovarian cancer subjects and that the set of three genes, CHEK1, AR, and LYN, can be used to classify good and poor prognostic tumors.
  
  
  CONCLUSIONS
  We provided a workflow using a Boolean logic schema for the identification of differentially expressed genes by integrating diverse biological information. This integrated approach resulted in the identification of genes as potential biomarkers in ovarian cancer.
authors: ARC Centre of Excellence in Bioinformatics and Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW 2109, Australia.
authors: Gaurav
authors: G
authors: Kumar
authors: Edmond J
authors: EJ
authors: Breen
authors: Shoba
authors: S
authors: Ranganathan
mesh_terms: D000071877:Checkpoint Kinase 1; D030541:Databases, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics*; D052138:Genes, Neoplasm / Q000235:genetics*; D056726:Genetic Association Studies / Q000379:methods*; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008957:Models, Genetic; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000503:physiopathology; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D049490:Systems Biology / Q000379:methods
chemical_list: D005819:Genetic Markers; D011494:Protein Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; D017346:Protein Serine-Threonine Kinases
references: Clin Cancer Res. 2001 Aug;7(8):2159-67
references: 11489789
references: Twin Res Hum Genet. 2011 Aug;14(4):328-32
references: 21787115
references: Nature. 2011 Jun 29;474(7353):609-15
references: 21720365
references: Hum Pathol. 2011 Mar;42(3):409-18
references: 21193224
references: Exp Cell Res. 2010 Dec 10;316(20):3425-34
references: 20619259
references: JAMA. 2002 Apr 3;287(13):1671-9
references: 11926891
references: Oncogene. 2006 May 18;25(21):3059-64
references: 16407832
references: J Natl Cancer Inst. 2001 Oct 3;93(19):1458-64
references: 11584061
references: J Clin Oncol. 2008 Jun 10;26(17):2846-53
references: 18539963
references: Nat Methods. 2007 Nov;4(11):879
references: 17971777
references: Science. 2002 Dec 6;298(5600):1912-34
references: 12471243
references: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D449-51
references: 14681454
references: J Proteomics. 2012 Jun 6;75(10):2758-72
references: 22366292
references: Am J Hum Genet. 2001 Jul;69(1):138-47
references: 11404819
references: Nucleic Acids Res. 2007 Jan;35(Database issue):D137-40
references: 17202159
references: Nat Rev Cancer. 2004 Mar;4(3):177-83
references: 14993899
references: Cell. 2011 Mar 4;144(5):646-74
references: 21376230
references: Mol Syst Biol. 2007;3:152
references: 18091723
references: BMC Genomics. 2011 Nov 30;12 Suppl 3:S19
references: 22369639
references: Nucleic Acids Res. 2010 Jan;38(Database issue):D211-22
references: 19920124
references: N Engl J Med. 1996 Jan 4;334(1):28-33
references: 7494569
references: J Biol Chem. 2008 Feb 29;283(9):5402-13
references: 18086677
references: Nature. 2006 Jan 19;439(7074):353-7
references: 16273092
references: Brief Bioinform. 2005 Jun;6(2):194-8
references: 15975228
references: PLoS Comput Biol. 2009 Dec;5(12):e1000601
references: 20011507
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D718-23
references: 20965963
references: Hum Genomics. 2011 Oct;5(6):709-17
references: 22155609
references: IUBMB Life. 2009 May;61(5):510-5
references: 19180666
references: J Ovarian Res. 2010 Jun 17;3:14
references: 20565760
references: Bioinformatics. 2006 Dec 1;22(23):2926-33
references: 17000751
references: Proc Natl Acad Sci U S A. 1999 May 11;96(10):5722-7
references: 10318951
references: Methods Mol Biol. 2009;577:67-79
references: 19718509
references: Nat Methods. 2010 Oct;7(10):801-5
references: 20936779
references: Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20870-5
references: 19104045
references: Anticancer Res. 2011 Jul;31(7):2541-5
references: 21873172
references: Cancer. 2011 Jun 15;117(12):2608-19
references: 21656738
references: Cell Cycle. 2008 Dec;7(23):3622-4
references: 19029796
references: Exp Mol Pathol. 2011 Oct;91(2):563-8
references: 21763306
references: Nucleic Acids Res. 2012 Oct;40(19):9379-91
references: 22879375
references: Biomedica. 2010 Oct-Dec;30(4):551-8
references: 21713359
references: J Clin Invest. 2010 Aug;120(8):2842-57
references: 20592473
references: Mol Cell Proteomics. 2006 Oct;5(10):1799-810
references: 16844681
references: Nucleic Acids Res. 2010 Jan;38(Database issue):D532-9
references: 19897547
references: Nucleic Acids Res. 2007 Jan;35(Database issue):D561-5
references: 17145710
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D945-50
references: 20952405
references: BMC Genomics. 2011 Oct 14;12:505
references: 21999571
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D1005-10
references: 21097893
references: Cell Mol Life Sci. 2008 Apr;65(7-8):1220-36
references: 18259688
references: Genet Epidemiol. 2005 Feb;28(2):157-70
references: 15532037
references: PLoS One. 2011;6(11):e24709
references: 22073136
references: J Cell Mol Med. 2011 Jul;15(7):1542-50
references: 20716114
references: Genome Biol. 2011 Jun 22;12(6):R57
references: 21696594
references: Bioinformatics. 2009 Jan 15;25(2):265-71
references: 19038985
references: Clin Cancer Res. 2011 Nov 15;17(22):7067-79
references: 21933891
references: Nucl Recept Signal. 2012;10:e001
references: 22438791
references: Cell. 2000 Jan 7;100(1):57-70
references: 10647931
references: Lung Cancer. 2011 Jul;73(1):38-44
references: 21095038
references: Genome Res. 2004 Apr;14(4):742-9
references: 15060018
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D698-704
references: 21071413
references: Nat Commun. 2010 Jul 13;1:34
references: 20975711
references: PLoS One. 2011 Mar 08;6(3):e17844
references: 21408081
references: Adv Genet. 2010;72:25-45
references: 21029847
references: Eur J Cancer. 2005 Nov;41(16):2462-78
references: 16213704
references: Nature. 2008 Sep 18;455(7211):401-5
references: 18724358
references: Nucleic Acids Res. 2003 Jan 1;31(1):272-4
references: 12520000
references: Nat Biotechnol. 2004 Feb;22(2):177-83
references: 14755292
references: Int J Cancer. 2011 Oct 15;129(8):1859-71
references: 21154811
references: Genome Biol. 2004;5(12):R100
references: 15575966
references: FEBS Lett. 2004 Aug 27;573(1-3):83-92
references: 15327980
references: Clin Cancer Res. 2009 Apr 1;15(7):2417-25
references: 19318489
references: Carcinogenesis. 2012 Sep;33(9):1684-91
references: 22791811
references: Cancer Cell. 2013 Jan 14;23(1):35-47
references: 23260764
references: Int J Oncol. 2011 Jul;39(1):225-34
references: 21573492
references: BMC Syst Biol. 2011 Feb 26;5:35
references: 21352556
references: J Cell Biol. 2011 Jun 13;193(6):1049-64
references: 21646403
references: Clin Cancer Res. 2010 Jan 15;16(2):376-83
references: 20068082