title: Protein-protein interaction reveals synergistic discrimination of cancer phenotype.
abstract: Cancer is a disease associated with the deregulation of multiple gene networks. Microarray data has permitted researchers to identify gene panel markers for diagnosis or prognosis of cancer but these are not sufficient to make specific mechanistic assertions about phenotype switches. We propose a strategy to identify putative mechanisms of cancer phenotypes by protein-protein interactions (PPI). We first extracted the logic status of a PPI via the relative expression of the corresponding gene pair. The joint association of a gene pair on a cancer phenotype was calculated by entropy minimization and assessed using a support vector machine. A typical predictor is "If Src high-expression, and Cav-1 low-expression, then cancer." We achieved 90% accuracy on test data with a majority of predictions associated with the MAPK pathway, focal adhesion, apoptosis and cell cycle. Our results can aid in the development of phenotype discrimination biomarkers and identification of putative therapeutic interference targets for drug development.
authors.affiliation: School of Computer Science, Wuhan University, Wuhan, P.R. China. laserxiong@gmail.com
authors.forename: Jianghui
authors.initials: J
authors.lastname: Xiong
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Simon
authors.initials: S
authors.lastname: Rayner
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Li
authors.forename: Shanguang
authors.initials: S
authors.lastname: Chen
references.citation: N Engl J Med. 2004 Dec 30;351(27):2817-26
references.pmid: 15591335
references.citation: Nature. 2006 Jan 19;439(7074):353-7
references.pmid: 16273092
references.citation: PLoS Comput Biol. 2006 Jun 16;2(6):e68
references.pmid: 16789819
references.citation: BMC Cancer. 2007 Sep 25;7:182
references.pmid: 17894856
references.citation: Lancet. 2005 Feb 19-25;365(9460):671-9
references.pmid: 15721472
references.citation: Cancer Res. 2004 May 1;64(9):2962-8
references.pmid: 15126326
references.citation: BMC Genomics. 2007 Jun 01;8:140
references.pmid: 17540040
references.citation: PLoS One. 2008 Apr 02;3(4):e1908
references.pmid: 18382681
references.citation: Nat Rev Genet. 2007 Aug;8(8):601-9
references.pmid: 17607306
references.citation: Bioinformatics. 2007 Nov 1;23(21):2866-72
references.pmid: 17925306
references.citation: Int J Med Inform. 2005 Aug;74(7-8):491-503
references.pmid: 15967710
references.citation: J Biol Chem. 1998 Aug 7;273(32):20448-55
references.pmid: 9685399
references.citation: J Natl Cancer Inst. 2006 Feb 15;98(4):262-72
references.pmid: 16478745
references.citation: Am J Pathol. 2003 Jun;162(6):2029-39
references.pmid: 12759258
references.citation: Am J Physiol Cell Physiol. 2005 Mar;288(3):C494-506
references.pmid: 15692148
references.citation: J Biol Chem. 2004 Dec 3;279(49):51630-46
references.pmid: 15355971
references.citation: N Engl J Med. 2002 Dec 19;347(25):1999-2009
references.pmid: 12490681
references.citation: J Biol Chem. 1999 Nov 5;274(45):32333-41
references.pmid: 10542274