title: Comparative network-based recovery analysis and proteomic profiling of neurological changes in valproic acid-treated mice.
abstract: Despite its prominence for characterization of complex mixtures, LC-MS/MS frequently fails to identify many proteins. Network-based analysis methods, based on protein-protein interaction networks (PPINs), biological pathways, and protein complexes, are useful for recovering non-detected proteins, thereby enhancing analytical resolution. However, network-based analysis methods do come in varied flavors for which the respective efficacies are largely unknown. We compare the recovery performance and functional insights from three distinct instances of PPIN-based approaches, viz., Proteomics Expansion Pipeline (PEP), Functional Class Scoring (FCS), and Maxlink, in a test scenario of valproic acid (VPA)-treated mice. We find that the most comprehensive functional insights, as well as best non-detected protein recovery performance, are derived from FCS utilizing real biological complexes. This outstrips other network-based methods such as Maxlink or Proteomics Expansion Pipeline (PEP). From FCS, we identified known biological complexes involved in epigenetic modifications, neuronal system development, and cytoskeletal rearrangements. This is congruent with the observed phenotype where adult mice showed an increase in dendritic branching to allow the rewiring of visual cortical circuitry and an improvement in their visual acuity when tested behaviorally. In addition, PEP also identified a novel complex, comprising YWHAB, NR1, NR2B, ACTB, and TJP1, which is functionally related to the observed phenotype. Although our results suggest different network analysis methods can produce different results, on the whole, the findings are mutually supportive. More critically, the non-overlapping information each provides can provide greater holistic understanding of complex phenotypes.
authors.affiliation: Department of Computing, Imperial College London, United Kingdom.
authors.forename: Wilson Wen Bin
authors.initials: WW
authors.lastname: Goh
authors.forename: Marek J
authors.initials: MJ
authors.lastname: Sergot
authors.forename: Judy C G
authors.initials: JC
authors.lastname: Sng
authors.forename: Judy Cg
authors.initials: JC
authors.lastname: Sng
authors.forename: Limsoon
authors.initials: L
authors.lastname: Wong
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D016000:Cluster Analysis; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058977:Molecular Sequence Annotation; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D025941:Protein Interaction Mapping / Q000379:methods; D060066:Protein Interaction Maps; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D059467:Transcriptome; D014635:Valproic Acid / Q000494:pharmacology*; D014793:Visual Cortex / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000927:Anticonvulsants; D046912:Multiprotein Complexes; D020543:Proteome; D014635:Valproic Acid
references.citation: BMC Bioinformatics. 2006 Nov 18;7:508
references.pmid: 17112386
references.citation: Curr Opin Biotechnol. 2013 Dec;24(6):1122-8
references.pmid: 23481377
references.citation: Learn Mem. 2008 Jan 03;15(1):39-45
references.pmid: 18174372
references.citation: Bioinformatics. 2010 Apr 15;26(8):1105-11
references.pmid: 20185405
references.citation: J Proteome Res. 2012 Mar 2;11(3):1571-81
references.pmid: 22243476
references.citation: Amino Acids. 2010 Apr;38(4):1237-52
references.pmid: 19669079
references.citation: J Proteome Res. 2010 Jan;9(1):472-84
references.pmid: 19916522
references.citation: Mol Biosyst. 2011 May;7(5):1728-41
references.pmid: 21423987
references.citation: J Proteome Res. 2011 May 6;10(5):2261-72
references.pmid: 21410269
references.citation: PLoS Comput Biol. 2011 Oct;7(10):e1002240
references.pmid: 22028643
references.citation: Neuropharmacology. 2007 Jan;52(1):200-14
references.pmid: 16895734
references.citation: Nat Methods. 2007 Mar;4(3):207-14
references.pmid: 17327847
references.citation: J Neurosci. 2010 Nov 10;30(45):14937-42
references.pmid: 21068295
references.citation: Mol Syst Biol. 2009;5:303
references.pmid: 19690572
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16659-64
references.pmid: 15537713
references.citation: Nucleic Acids Res. 2010 Jan;38(Database issue):D497-501
references.pmid: 19884131
references.citation: Neuropsychopharmacology. 2010 Feb;35(3):792-805
references.pmid: 19924110
references.citation: Bioinformatics. 2006 Apr 15;22(8):1021-3
references.pmid: 16473872
references.citation: Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2854-9
references.pmid: 12591944
references.citation: Eur J Neurosci. 2010 Jun;31(12):2185-92
references.pmid: 20550570
references.citation: Science. 2008 Apr 18;320(5874):385-8
references.pmid: 18420937
references.citation: J Neurochem. 2003 Apr;85(1):193-205
references.pmid: 12641741
references.citation: J Neurosci. 2011 Oct 19;31(42):15163-72
references.pmid: 22016550
references.citation: Bioinformatics. 2012 Feb 15;28(4):453-6
references.pmid: 22180412
references.citation: J Neurosci. 2006 Aug 2;26(31):8137-47
references.pmid: 16885227
references.citation: Neuron. 2012 Feb 9;73(3):497-510
references.pmid: 22325202
references.citation: Proteomics. 2012 Feb;12(4-5):550-63
references.pmid: 22247042
references.citation: Neuron. 2007 Jul 19;55(2):201-15
references.pmid: 17640523
references.citation: Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14698-701
references.pmid: 11734655
references.citation: Mol Cell Proteomics. 2010 Apr;9(4):648-55
references.pmid: 19959820
references.citation: Nature. 2009 May 7;459(7243):55-60
references.pmid: 19424149
references.citation: Curr Opin Genet Dev. 2006 Oct;16(5):502-7
references.pmid: 16844365
references.citation: Pac Symp Biocomput. 2002;:474-85
references.pmid: 11928500
references.citation: BMC Genomics. 2013 Jan 16;14:35
references.pmid: 23324392
references.citation: J Proteome Res. 2011 Nov 4;10(11):5070-83
references.pmid: 21913717
references.citation: Philos Trans R Soc Lond B Biol Sci. 2003 Apr 29;358(1432):649-55
references.pmid: 12740110
references.citation: Neuron. 2011 Apr 14;70(1):35-42
references.pmid: 21482354
references.citation: Neuron. 2007 Mar 1;53(5):747-59
references.pmid: 17329213
references.citation: Science. 2004 Mar 12;303(5664):1681-3
references.pmid: 15017002
references.citation: Proteomics. 2004 Jul;4(7):1985-8
references.pmid: 15221759
references.citation: Neuron. 2007 Feb 15;53(4):495-502
references.pmid: 17296552