title: Identification of highly synchronized subnetworks from gene expression data.
abstract: BACKGROUND
  There has been a growing interest in identifying context-specific active protein-protein interaction (PPI) subnetworks through integration of PPI and time course gene expression data. However the interaction dynamics during the biological process under study has not been sufficiently considered previously.
  
  
  METHODS
  Here we propose a topology-phase locking (TopoPL) based scoring metric for identifying active PPI subnetworks from time series expression data. First the temporal coordination in gene expression changes is evaluated through phase locking analysis; The results are subsequently integrated with PPI to define an activity score for each PPI subnetwork, based on individual member expression, as well topological characteristics of the PPI network and of the expression temporal coordination network; Lastly, the subnetworks with the top scores in the whole PPI network are identified through simulated annealing search.
  
  
  RESULTS
  Application of TopoPL to simulated data and to the yeast cell cycle data showed that it can more sensitively identify biologically meaningful subnetworks than the method that only utilizes the static PPI topology, or the additive scoring method. Using TopoPL we identified a core subnetwork with 49 genes important to yeast cell cycle. Interestingly, this core contains a protein complex known to be related to arrangement of ribosome subunits that exhibit extremely high gene expression synchronization.
  
  
  CONCLUSIONS
  Inclusion of interaction dynamics is important to the identification of relevant gene networks.
authors.affiliation: Department of Physics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Shouguo
authors.initials: S
authors.lastname: Gao
authors.forename: Xujing
authors.initials: X
authors.lastname: Wang
mesh_terms: D000465:Algorithms; D002453:Cell Cycle; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks; D017711:Nonlinear Dynamics; D025941:Protein Interaction Mapping / Q000379:methods*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics
references.citation: Cell. 2001 Sep 21;106(6):697-708
references.pmid: 11572776
references.citation: Bioinformatics. 2012 Jul 15;28(14):1873-8
references.pmid: 22576179
references.citation: Bioinformatics. 2006 Jul 1;22(13):1600-7
references.pmid: 16606683
references.citation: J Biosci Bioeng. 2012 Jul;114(1):17-22
references.pmid: 22608550
references.citation: Trends Genet. 2003 Aug;19(8):422-7
references.pmid: 12902159
references.citation: Cell. 1996 Mar 8;84(5):699-709
references.pmid: 8625408
references.citation: Nature. 2004 Jul 1;430(6995):88-93
references.pmid: 15190252
references.citation: PLoS Comput Biol. 2006 Dec 29;2(12):e174
references.pmid: 17196032
references.citation: Plant Physiol. 2009 Nov;151(3):1486-97
references.pmid: 19734265
references.citation: Bioinformatics. 2007 Nov 15;23(22):3100-2
references.pmid: 17890270
references.citation: Genome Res. 2003 Nov;13(11):2450-4
references.pmid: 14559778
references.citation: Genome Biol. 2010;11(3):R24
references.pmid: 20193063
references.citation: BMC Syst Biol. 2010 Dec 03;4:167
references.pmid: 21129191
references.citation: Genome Res. 2009 Apr;19(4):556-66
references.pmid: 19158363
references.citation: Bioinformatics. 2006 Feb 15;22(4):507-8
references.pmid: 16357033
references.citation: Bioinformatics. 2007 Aug 15;23(16):2121-8
references.pmid: 17545181
references.citation: Brief Bioinform. 2010 Jan;11(1):15-29
references.pmid: 20061351
references.citation: Science. 2005 Feb 4;307(5710):724-7
references.pmid: 15692050
references.citation: Yeast. 2011 Apr;28(4):293-308
references.pmid: 21456055
references.citation: BMC Bioinformatics. 2011 Aug 15;12:339
references.pmid: 21849017
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W245-52
references.pmid: 17576675
references.citation: Eukaryot Cell. 2002 Apr;1(2):229-40
references.pmid: 12455957
references.citation: Nature. 2006 Mar 30;440(7084):631-6
references.pmid: 16429126
references.citation: Pac Symp Biocomput. 2009;:203-14
references.pmid: 19209702
references.citation: Phys Biol. 2005 Jun;2(2):S24-35
references.pmid: 16204846
references.citation: OMICS. 2012 Oct;16(10):566-78
references.pmid: 22917479