title: Inferring cell-scale signalling networks via compressive sensing.
abstract: Signalling network inference is a central problem in system biology. Previous studies investigate this problem by independently inferring local signalling networks and then linking them together via crosstalk. Since a cellular signalling system is in fact indivisible, this reductionistic approach may have an impact on the accuracy of the inference results. Preferably, a cell-scale signalling network should be inferred as a whole. However, the holistic approach suffers from three practical issues: scalability, measurement and overfitting. Here we make this approach feasible based on two key observations: 1) variations of concentrations are sparse due to separations of timescales; 2) several species can be measured together using cross-reactivity. We propose a method, CCELL, for cell-scale signalling network inference from time series generated by immunoprecipitation using Bayesian compressive sensing. A set of benchmark networks with varying numbers of time-variant species is used to demonstrate the effectiveness of our method. Instead of exhaustively measuring all individual species, high accuracy is achieved from relatively few measurements.
authors.affiliation: Department of Computing, Imperial College London, London, United Kingdom; Institute of Computing Technology, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Nie
authors.affiliation: Department of Computing, Imperial College London, London, United Kingdom.
authors.forename: Xian
authors.initials: X
authors.lastname: Yang
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Adcock
authors.affiliation: Institute of Computing Technology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Computing, Imperial College London, London, United Kingdom.
authors.forename: Yike
authors.initials: Y
authors.lastname: Guo
mesh_terms: D001499:Bayes Theorem; D012372:ROC Curve; D015398:Signal Transduction; D049490:Systems Biology
references.citation: Bioinformatics. 1998;14(10):869-83
references.pmid: 9927716
references.citation: FASEB J. 2008 Apr;22(4):954-65
references.pmid: 18039929
references.citation: Bioinformatics. 2008 Feb 15;24(4):553-60
references.pmid: 18175769
references.citation: Invest Ophthalmol Vis Sci. 2006 Dec;47(12):5267-75
references.pmid: 17122112
references.citation: Science. 1999 Apr 2;284(5411):92-6
references.pmid: 10102825
references.citation: Science. 1999 Jan 15;283(5400):381-7
references.pmid: 9888852
references.citation: Bioinformatics. 2004 Aug 12;20(12):1877-86
references.pmid: 15037511
references.citation: BMC Syst Biol. 2009 Feb 23;3:25
references.pmid: 19236711
references.citation: PLoS One. 2008;3(11):e3758
references.pmid: 19018286
references.citation: Carcinogenesis. 2010 Jan;31(1):2-8
references.pmid: 19861649
references.citation: Curr Protoc Immunol. 2001 May;Chapter 8:Unit 8.3
references.pmid: 18432858
references.citation: Proc Am Thorac Soc. 2004;1(3):239-46
references.pmid: 16113441
references.citation: J Biol Chem. 2002 May 10;277(19):17263-70
references.pmid: 11867630
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6163-8
references.pmid: 11983907
references.citation: Biophys J. 2004 Jul;87(1):37-46
references.pmid: 15240442
references.citation: Genome Res. 2003 Jun;13(6B):1443-54
references.pmid: 12819143
references.citation: Science. 2002 Dec 6;298(5600):1912-34
references.pmid: 12471243
references.citation: FEBS J. 2005 May;272(9):2141-51
references.pmid: 15853799
references.citation: J R Soc Interface. 2009 Feb 6;6(31):187-202
references.pmid: 19205079
references.citation: Biosystems. 2009 Apr;96(1):86-103
references.pmid: 19150482
references.citation: Biochem J. 2000 Oct 15;351 Pt 2:289-305
references.pmid: 11023813
references.citation: Bioinformatics. 2007 Dec 1;23(23):3209-16
references.pmid: 18042557
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1028-33
references.pmid: 12552139
references.citation: Biotechnol Prog. 2008 Jan-Feb;24(1):96-109
references.pmid: 17918858
references.citation: Nat Rev Mol Cell Biol. 2010 Jun;11(6):427-39
references.pmid: 20461098
references.citation: Mass Spectrom Rev. 2010 Jan-Feb;29(1):29-54
references.pmid: 19263479
references.citation: Cell Res. 2009 Jan;19(1):71-88
references.pmid: 19002158