title: Meta-analysis and profiling of cardiac expression modules.
abstract: Heart failure is a complex, complicated disease that is not yet fully understood. We used the Module Map algorithm to uncover groups of genes that have a similar pattern of expression under various conditions of heart stress. These groups of genes are called modules and may serve as computational predictions of biological pathways for the various clinical situations. The Module Map algorithm allows a large-scale analysis of genes expressed. We applied this algorithm to 700 different mouse experiments downloaded from the Gene Expression Omnibus database, which identified 884 modules. The analysis reconstructed partially known principles that play a role in governing the response of heart to stress, thus demonstrating the strength of the method. We have shown a role of genes related to the immune system in conditions of heart remodeling and failure. We have also shown changes in the expression of genes involved with energy metabolism and changes in the expression of contractile proteins of the heart following myocardial infarction. When focusing on another module we noted a new correlation between genes related to osteogenesis and heart failure, including Runx2 and Ahsg, whose role in heart failure was unknown so far. Despite a lack of prior biological knowledge, the Module Map algorithm has reconstructed known pathways, which demonstrates the strength of this new method for analyzing gene profiles related to clinical phenomenon. The method and the analysis presented are a new avenue to uncover the correlation of clinical conditions to the molecular level.
authors.affiliation: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel.
authors.forename: Uri David
authors.initials: UD
authors.lastname: Akavia
authors.forename: Dafna
authors.initials: D
authors.lastname: Benayahu
mesh_terms: D000465:Algorithms; D000818:Animals; D020869:Gene Expression Profiling / Q000706:statistics & numerical data*; D051379:Mice; D009203:Myocardial Infarction / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis
references.citation: Nat Genet. 2004 Oct;36(10):1090-8
references.pmid: 15448693
references.citation: J Biol Chem. 1986 Feb 5;261(4):1838-43
references.pmid: 3944112
references.citation: Trends Cardiovasc Med. 1993 Jan-Feb;3(1):12-7
references.pmid: 21244965
references.citation: J Biol Chem. 1986 Mar 25;261(9):4337-45
references.pmid: 3456347
references.citation: Nat Genet. 1999 Jul;22(3):281-5
references.pmid: 10391217
references.citation: Genome Biol. 2005;6(1):R7
references.pmid: 15642099
references.citation: J Cell Biol. 1990 Dec;111(6 Pt 1):2427-36
references.pmid: 2277065
references.citation: Trends Cell Biol. 2003 Apr;13(4):163-5
references.pmid: 12667752
references.citation: J Immunol. 2001 Sep 15;167(6):3223-30
references.pmid: 11544309
references.citation: Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4058-63
references.pmid: 10737769
references.citation: Cell. 1997 May 30;89(5):765-71
references.pmid: 9182764
references.citation: Cell. 1997 May 30;89(5):747-54
references.pmid: 9182762
references.citation: Clin Sci (Lond). 2003 Sep;105(3):273-8
references.pmid: 12725640
references.citation: Curr Control Trials Cardiovasc Med. 2001;2(6):271-277
references.pmid: 11806813
references.citation: J Immunol. 2002 Nov 15;169(10):5410-4
references.pmid: 12421915
references.citation: Cardiovasc Res. 2007 May 1;74(2):184-95
references.pmid: 17109837
references.citation: Cell Motil Cytoskeleton. 2004 Jun;58(2):104-11
references.pmid: 15083532
references.citation: BMC Bioinformatics. 2007 Jul 30;8:273
references.pmid: 17663764
references.citation: J Clin Invest. 1998 Apr 1;101(7):1385-93
references.pmid: 9525981
references.citation: J Mol Cell Cardiol. 2005 Mar;38(3):425-32
references.pmid: 15733902
references.citation: Mol Biol Cell. 2005 Feb;16(2):649-64
references.pmid: 15548599
references.citation: Eur J Cell Biol. 1995 Nov;68(3):330-5
references.pmid: 8603686
references.citation: Nat Rev Mol Cell Biol. 2006 Oct;7(10):713-26
references.pmid: 16990851
references.citation: J Cell Sci. 2003 Nov 15;116(Pt 22):4605-13
references.pmid: 14576354
references.citation: J Biol Chem. 1984 May 25;259(10):6437-46
references.pmid: 6327679
references.citation: Matrix Biol. 1998 Feb;16(7):387-98
references.pmid: 9524359
references.citation: J Cell Sci. 2006 May 1;119(Pt 9):1947-60
references.pmid: 16636079
references.citation: Biochem J. 2003 Nov 15;376(Pt 1):135-45
references.pmid: 12943536
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2981-6
references.pmid: 14973197
references.citation: Genes Dev. 1997 Aug 15;11(16):2052-65
references.pmid: 9284045
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D354-7
references.pmid: 16381885
references.citation: Curr Biol. 2004 Sep 21;14(18):1685-93
references.pmid: 15380073
references.citation: Clin Exp Nephrol. 2007 Dec;11(4):304-308
references.pmid: 18085392
references.citation: J Biol Chem. 2002 Nov 22;277(47):45566-71
references.pmid: 12297504
references.citation: Nature. 2005 Sep 8;437(7056):270-4
references.pmid: 16025100
references.citation: Circ Res. 1981 Jul;49(1):80-8
references.pmid: 7237703
references.citation: J Am Soc Nephrol. 2005 Nov;16(11):3357-64
references.pmid: 16177000
references.citation: Physiol Rev. 1999 Oct;79(4):1157-91
references.pmid: 10508232
references.citation: J Cell Biochem. 2006 Jan 1;97(1):33-44
references.pmid: 16215986
references.citation: Heart Fail Rev. 2000 Oct;5(3):239-50
references.pmid: 16228907
references.citation: Nat Genet. 2003 Jun;34(2):166-76
references.pmid: 12740579
references.citation: PLoS Biol. 2004 Jan;2(1):E9
references.pmid: 14737187
references.citation: Circulation. 2001 Dec 11;104(24):2923-31
references.pmid: 11739307
references.citation: Nat Genet. 2000 May;25(1):25-9
references.pmid: 10802651
references.citation: J Biol Chem. 1991 May 15;266(14):9180-5
references.pmid: 2026617
references.citation: J Am Coll Cardiol. 2006 Oct 17;48(8):1610-7
references.pmid: 17045896
references.citation: Kidney Int. 2005 Jun;67(6):2383-92
references.pmid: 15882283
references.citation: Science. 1998 Jan 23;279(5350):527-33
references.pmid: 9438839
references.citation: Mech Dev. 2003 Aug;120(8):851-64
references.pmid: 12963107
references.citation: Hypertens Res. 2005 Jun;28(6):483-90
references.pmid: 16231753
references.citation: J Cell Physiol. 2008 Sep;216(3):663-72
references.pmid: 18449863
references.citation: Nucleic Acids Res. 2007 Jan;35(Database issue):D618-23
references.pmid: 17130151
references.citation: Physiol Rev. 2005 Jul;85(3):1093-129
references.pmid: 15987803
references.citation: N Engl J Med. 2003 May 15;348(20):2007-18
references.pmid: 12748317
references.citation: Nephrol Dial Transplant. 2005 Aug;20(8):1676-85
references.pmid: 15899935
references.citation: Ann N Y Acad Sci. 2006 Dec;1091:205-17
references.pmid: 17341615
references.citation: Mol Cell Biochem. 2007 Jun;300(1-2):1-7
references.pmid: 17136480
references.citation: Anat Rec. 2002 Apr 1;266(4):194-7
references.pmid: 11920381
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D135-9
references.pmid: 16381831
references.citation: Bioinformatics. 2006 Aug 15;22(16):2053-4
references.pmid: 16787974
references.citation: Gene. 2008 Aug 1;419(1-2):27-34
references.pmid: 18538509
references.citation: Circ Res. 1999 Apr 2;84(6):729-34
references.pmid: 10189361
references.citation: Mol Endocrinol. 1993 Nov;7(11):1445-55
references.pmid: 7906861
references.citation: Pharmacol Ther. 2007 Jun;114(3):278-94
references.pmid: 17499363
references.citation: FASEB J. 1993 Dec;7(15):1475-82
references.pmid: 8262332
references.citation: J Mol Cell Cardiol. 1996 Jul;28(7):1531-8
references.pmid: 8841940
references.citation: J Biol Chem. 2006 Mar 17;281(11):7228-36
references.pmid: 16407299
references.citation: Med Princ Pract. 2007;16(2):81-9
references.pmid: 17303941
references.citation: Anat Embryol (Berl). 2005 Aug;210(1):13-23
references.pmid: 16034610
references.citation: Nucleic Acids Res. 2007 Jan;35(Database issue):D760-5
references.pmid: 17099226
references.citation: Microsc Res Tech. 2000 Sep 15;50(6):522-31
references.pmid: 10998641
references.citation: Semin Cell Dev Biol. 2007 Feb;18(1):84-9
references.pmid: 17267246
references.citation: Nat Cell Biol. 2007 Mar;9(3):299-309
references.pmid: 17310241
references.citation: Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5
references.pmid: 12883005
references.citation: Biochem Biophys Res Commun. 2002 Mar 22;292(1):121-7
references.pmid: 11890681
references.citation: FASEB J. 1999 Oct;13(13):1774-86
references.pmid: 10506580
references.citation: Immunity. 2003 Jul;19(1):95-104
references.pmid: 12871642
references.citation: Circ Res. 1988 Apr;62(4):757-65
references.pmid: 2964945
references.citation: BMC Genomics. 2006 Apr 27;7:95
references.pmid: 16643645
references.citation: Bioinformatics. 2002;18 Suppl 1:S136-44
references.pmid: 12169541
references.citation: Nat Genet. 2002 Aug;31(4):370-7
references.pmid: 12134151
references.citation: Eur J Cell Biol. 2006 May;85(5):423-31
references.pmid: 16487626
references.citation: Science. 2003 Oct 10;302(5643):249-55
references.pmid: 12934013
references.citation: Biochem J. 1997 Nov 15;328 ( Pt 1):105-12
references.pmid: 9359840
references.citation: Am J Physiol Heart Circ Physiol. 2005 Aug;289(2):H643-51
references.pmid: 16014617
references.citation: J Biol Chem. 2006 Nov 24;281(47):35873-83
references.pmid: 17020881
references.citation: Nature. 2005 Mar 17;434(7031):338-45
references.pmid: 15735639
references.citation: Dev Biol. 1991 Dec;148(2):442-58
references.pmid: 1743394
references.citation: Biochem J. 2002 Oct 15;367(Pt 2):413-22
references.pmid: 12119049
references.citation: Mol Cell Neurosci. 1997;9(5-6):460-75
references.pmid: 9361282
references.citation: Physiol Rev. 1996 Apr;76(2):371-423
references.pmid: 8618961
references.citation: J Biol Chem. 2002 Dec 20;277(51):50112-20
references.pmid: 12384505
references.citation: J Biol Chem. 1999 Aug 6;274(32):22251-6
references.pmid: 10428792
references.citation: Blood. 2006 Apr 1;107(7):2777-85
references.pmid: 16368891
references.citation: Nat Genet. 2004 Feb;36(2):197-204
references.pmid: 14730301
references.citation: Dev Dyn. 2003 Dec;228(4):643-50
references.pmid: 14648841
references.citation: Am J Physiol. 1994 Jul;267(1 Pt 2):H400-5
references.pmid: 8048605
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4465-70
references.pmid: 11904358