A semi-parametric Bayesian model for unsupervised differential co-expression analysis.
BACKGROUND
Differential co-expression analysis is an emerging strategy for characterizing disease related dysregulation of gene expression regulatory networks. Given pre-defined sets of biological samples, such analysis aims at identifying genes that are co-expressed in one, but not in the other set of samples.


RESULTS
We developed a novel probabilistic framework for jointly uncovering contexts (i.e. groups of samples) with specific co-expression patterns, and groups of genes with different co-expression patterns across such contexts. In contrast to current clustering and bi-clustering procedures, the implicit similarity measure in this model used for grouping biological samples is based on the clustering structure of genes within each sample and not on traditional measures of gene expression level similarities. Within this framework, biological samples with widely discordant expression patterns can be placed in the same context as long as the co-clustering structure of genes is concordant within these samples. To the best of our knowledge, this is the first method to date for unsupervised differential co-expression analysis in this generality. When applied to the problem of identifying molecular subtypes of breast cancer, our method identified reproducible patterns of differential co-expression across several independent expression datasets. Sample groupings induced by these patterns were highly informative of the disease outcome. Expression patterns of differentially co-expressed genes provided new insights into the complex nature of the ERalpha regulatory network.


CONCLUSIONS
We demonstrated that the use of the co-clustering structure as the similarity measure in the unsupervised analysis of sample gene expression profiles provides valuable information about expression regulatory networks.
Freudenberg
Johannes M
JM
Laboratory for Statistical Genomics and Systems Biology, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati OH 45267-0056, USA.
Sivaganesan
Siva
S
Wagner
Michael
M
Medvedovic
Mario
M
D001499:Bayes Theorem; D001943:Breast Neoplasms / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D053263:Gene Regulatory Networks
J Mol Endocrinol. 2005 Apr;34(2):535-51
15821115
Bioinformatics. 2006 May 1;22(9):1122-9
16500941
Bioinformatics. 2005 Dec 15;21(24):4348-55
16234317
Endocr Relat Cancer. 2009 Dec;16(4):1073-89
19628648
OMICS. 2006 Winter;10(4):507-31
17233561
Nucleic Acids Res. 2008 Jan;36(1):76-93
17986456
Bioinformatics. 2002 Sep;18(9):1194-206
12217911
BMC Bioinformatics. 2009 Jul 29;10:234
19640299
Bioinformatics. 2004 Nov 22;20(17):3146-55
15231528
Bioinformatics. 2006 Jul 15;22(14):1737-44
16709591
Bioinformatics. 2004 Aug 4;20 Suppl 1:i194-9
15262799
BMC Bioinformatics. 2009 Apr 16;10:109
19371436
Bioinformatics. 2009 Nov 1;25(21):2780-6
19689953
J Natl Cancer Inst. 2006 Feb 15;98(4):262-72
16478745
Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13550-5
16141321
BMC Med Genomics. 2008 Apr 25;1:11
18439262
Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8418-23
12829800
Nature. 2006 Jan 19;439(7074):353-7
16273092
Nature. 2002 Jan 31;415(6871):530-6
11823860
Proc Int Conf Intell Syst Mol Biol. 2000;8:93-103
10977070
Nucleic Acids Res. 2005 Nov 10;33(20):e175
16284200
Bioinformatics. 2004 May 22;20(8):1222-32
14871871
Bioinformatics. 2009 Dec 15;25(24):3267-74
19825796
BMC Genomics. 2008 May 22;9:239
18498629
BMC Bioinformatics. 2006 Nov 20;7:509
17116249
Nature. 2000 Aug 17;406(6797):747-52
10963602
Nat Biotechnol. 2003 Nov;21(11):1337-42
14555958
Nat Genet. 2003 Jun;34(2):166-76
12740579
Nat Genet. 2006 Nov;38(11):1289-97
17013392
BMC Genomics. 2010 Jan 13;11:27
20070909
Breast Cancer Res. 2005;7(6):R953-64
16280042
Clin Cancer Res. 2007 Jun 1;13(11):3207-14
17545524
Nat Rev Genet. 2006 Jan;7(1):55-65
16369572
BMC Bioinformatics. 2006 Jun 02;7:280
16749936
Nucleic Acids Res. 2009 Jan;37(Database issue):D885-90
18940857
Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10869-74
11553815
Bioinformatics. 2006 May 15;22(10):1282-3
16551664
PLoS Comput Biol. 2009 May;5(5):e1000382
19412532
Comput Biol Med. 2008 Mar;38(3):283-93
18061589
Bioinformatics. 2008 Oct 1;24(19):2200-8
18635567
Science. 2005 Oct 28;310(5748):644-8
16254181
Bioinformatics. 2002;18 Suppl 1:S136-44
12169541
Bioinformatics. 2009 Jan 15;25(2):211-7
19038984
Bioinformatics. 2003 Jan 22;19(2):185-93
12538238
N Engl J Med. 2009 Feb 19;360(8):790-800
19228622
Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6745-50
10359783
Bioinformatics. 2007 Jan 1;23(1):50-6
17090578
Cancer Res. 2008 Jul 1;68(13):5405-13
18593943
BMC Genomics. 2006 Apr 27;7:96
16643655
BMC Bioinformatics. 2007 Aug 03;8:283
17683565