title: Double and multiple knockout simulations for genome-scale metabolic network reconstructions.
abstract: BACKGROUND
  Constraint-based modeling of genome-scale metabolic network reconstructions has become a widely used approach in computational biology. Flux coupling analysis is a constraint-based method that analyses the impact of single reaction knockouts on other reactions in the network.
  
  
  RESULTS
  We present an extension of flux coupling analysis for double and multiple gene or reaction knockouts, and develop corresponding algorithms for an in silico simulation. To evaluate our method, we perform a full single and double knockout analysis on a selection of genome-scale metabolic network reconstructions and compare the results.
  A prototype implementation of double knockout simulation is available at http://hoverboard.io/L4FC.
authors: FB Mathematik und Informatik, Freie Universität Berlin, Arnimallee 6, Berlin, 14195 Germany.
authors: Yaron Ab
authors: YA
authors: Goldstein
authors: FB Mathematik und Informatik, Freie Universität Berlin, Arnimallee 6, Berlin, 14195 Germany.
authors: Alexander
authors: A
authors: Bockmayr
keywords: Constraint-based modeling; Flux coupling analysis; Gene knockout; Metabolic network; Reaction knockout
references: BMC Bioinformatics. 2010 Apr 29;11:213
references: 20426874
references: Gene. 2013 May 25;521(1):1-14
references: 23537990
references: Bioinformatics. 2010 Feb 15;26(4):536-43
references: 20031969
references: Bioinformatics. 2004 Jan 22;20(2):226-34
references: 14734314
references: Nat Rev Genet. 2014 Feb;15(2):107-20
references: 24430943
references: Biotechnol Bioeng. 2003 Dec 20;84(6):647-57
references: 14595777
references: Mol Syst Biol. 2009;5:301
references: 19690570
references: Mol Syst Biol. 2009;5:296
references: 19690565
references: PLoS Comput Biol. 2014 Jan;10(1):e1003378
references: 24391481
references: Nat Rev Microbiol. 2012 Feb 27;10(4):291-305
references: 22367118
references: Bioinformatics. 1999 Mar;15(3):251-7
references: 10222413
references: Genome Res. 2004 Feb;14(2):301-12
references: 14718379
references: BMC Bioinformatics. 2005 Dec 23;6:308
references: 16375763
references: BMC Syst Biol. 2010 Apr 19;4:45
references: 20403172
references: BMC Bioinformatics. 2012 Apr 23;13:57
references: 22524245
references: Biotechnol Bioeng. 1994 Feb 20;43(4):275-85
references: 18615690
references: Nat Biotechnol. 2010 Mar;28(3):245-8
references: 20212490
references: Metab Eng. 2012 Nov;14(6):672-86
references: 23026121
references: Bioinformatics. 2014 Apr 1;30(7):981-7
references: 24257186
references: BMC Bioinformatics. 2013 Nov 06;14:318
references: 24191903
references: Bioinformatics. 2013 Sep 1;29(17):2178-85
references: 23828783