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Network Analysis of Integrin Adhesion Complexes

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The Integrin Interactome

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2217))

Abstract

Cell-surface adhesion receptors mediate interactions with the extracellular matrix (ECM) to control many fundamental aspects of cell behavior, including cell migration, survival, and proliferation. Integrin adhesion receptors recruit structural and signaling proteins to form multimolecular adhesion complexes that link the plasma membrane to the actomyosin cytoskeleton. The assembly and turnover of adhesion complexes are tightly regulated, governed in part by the networks of physical protein interactions and functional signaling associations between components of the adhesome. Proteomic profiling of adhesion complexes has begun to reveal their molecular complexity and diversity. To interrogate the composition of cell–ECM adhesions, we detail herein an approach for the network analysis of adhesion complex proteomes. Integration of these proteomic data with adhesome databases in the context of predicted protein interactions enables the mapping of experimentally defined adhesion complex networks. Computational analysis of resultant network models can identify subnetworks of putative functionally linked adhesion protein communities. This approach provides a framework to predict functional adhesion protein relationships and generate new mechanistic hypotheses for further experimental testing.

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References

  1. Byron A, Morgan MR, Humphries MJ (2010) Adhesion signalling complexes. Curr Biol 20(24):R1063–R1067. https://doi.org/10.1016/j.cub.2010.10.059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Case LB, Waterman CM (2015) Integration of actin dynamics and cell adhesion by a three-dimensional, mechanosensitive molecular clutch. Nat Cell Biol 17(8):955–963. https://doi.org/10.1038/ncb3191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sun Z, Guo SS, Fassler R (2016) Integrin-mediated mechanotransduction. J Cell Biol 215(4):445–456. https://doi.org/10.1083/jcb.201609037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kechagia JZ, Ivaska J, Roca-Cusachs P (2019) Integrins as biomechanical sensors of the microenvironment. Nat Rev Mol Cell Biol 20(8):457–473. https://doi.org/10.1038/s41580-019-0134-2

    Article  CAS  PubMed  Google Scholar 

  5. Moreno-Layseca P, Streuli CH (2014) Signalling pathways linking integrins with cell cycle progression. Matrix Biol 34:144–153. https://doi.org/10.1016/j.matbio.2013.10.011

    Article  CAS  PubMed  Google Scholar 

  6. Humphries JD, Paul NR, Humphries MJ, Morgan MR (2015) Emerging properties of adhesion complexes: what are they and what do they do? Trends Cell Biol 25(7):388–397. https://doi.org/10.1016/j.tcb.2015.02.008

    Article  CAS  PubMed  Google Scholar 

  7. Doyle AD, Yamada KM (2016) Mechanosensing via cell-matrix adhesions in 3D microenvironments. Exp Cell Res 343(1):60–66. https://doi.org/10.1016/j.yexcr.2015.10.033

    Article  CAS  PubMed  Google Scholar 

  8. Green HJ, Brown NH (2019) Integrin intracellular machinery in action. Exp Cell Res 378(2):226–231. https://doi.org/10.1016/j.yexcr.2019.03.011

    Article  CAS  PubMed  Google Scholar 

  9. Winograd-Katz SE, Fassler R, Geiger B, Legate KR (2014) The integrin adhesome: from genes and proteins to human disease. Nat Rev Mol Cell Biol 15(4):273–288. https://doi.org/10.1038/nrm3769

    Article  CAS  PubMed  Google Scholar 

  10. Hamidi H, Ivaska J (2018) Every step of the way: integrins in cancer progression and metastasis. Nat Rev Cancer 18(9):533–548. https://doi.org/10.1038/s41568-018-0038-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cooper J, Giancotti FG (2019) Integrin signaling in cancer: mechanotransduction, stemness, epithelial plasticity, and therapeutic resistance. Cancer Cell 35(3):347–367. https://doi.org/10.1016/j.ccell.2019.01.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Janiszewska M, Primi MC, Izard T (2020) Cell adhesion in cancer: beyond the migration of single cells. J Biol Chem 295(8):2495–2505. https://doi.org/10.1074/jbc.REV119.007759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zaidel-Bar R, Itzkovitz S, Ma'ayan A, Iyengar R, Geiger B (2007) Functional atlas of the integrin adhesome. Nat Cell Biol 9(8):858–867. https://doi.org/10.1038/ncb0807-858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Byron A, Humphries JD, Bass MD, Knight D, Humphries MJ (2011) Proteomic analysis of integrin adhesion complexes. Sci Signal 4(167):pt2. https://doi.org/10.1126/scisignal.2001827

    Article  PubMed  Google Scholar 

  15. Geiger T, Zaidel-Bar R (2012) Opening the floodgates: proteomics and the integrin adhesome. Curr Opin Cell Biol 24(5):562–568. https://doi.org/10.1016/j.ceb.2012.05.004

    Article  CAS  PubMed  Google Scholar 

  16. Kuo JC, Han X, Yates JR 3rd, Waterman CM (2012) Isolation of focal adhesion proteins for biochemical and proteomic analysis. Methods Mol Biol 757:297–323. https://doi.org/10.1007/978-1-61779-166-6_19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jones MC, Humphries JD, Byron A, Millon-Fremillon A, Robertson J, Paul NR, Ng DHJ, Askari JA, Humphries MJ (2015) Isolation of integrin-based adhesion complexes. Curr Protoc Cell Biol 66:9.8.1–9.8.15. https://doi.org/10.1002/0471143030.cb0908s66

    Article  Google Scholar 

  18. Manninen A, Varjosalo M (2017) A proteomics view on integrin-mediated adhesions. Proteomics 17(3–4). https://doi.org/10.1002/pmic.201600022

  19. Robertson J, Humphries JD, Paul NR, Warwood S, Knight D, Byron A, Humphries MJ (2017) Characterization of the phospho-adhesome by mass spectrometry-based proteomics. Methods Mol Biol 1636:235–251. https://doi.org/10.1007/978-1-4939-7154-1_15

    Article  CAS  PubMed  Google Scholar 

  20. Byron A (2018) Proteomic profiling of integrin adhesion complex assembly. Methods Mol Biol 1764:193–236. https://doi.org/10.1007/978-1-4939-7759-8_13

    Article  CAS  PubMed  Google Scholar 

  21. Humphries JD, Byron A, Bass MD, Craig SE, Pinney JW, Knight D, Humphries MJ (2009) Proteomic analysis of integrin-associated complexes identifies RCC2 as a dual regulator of Rac1 and Arf6. Sci Signal 2(87):ra51. https://doi.org/10.1126/scisignal.2000396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Schiller HB, Friedel CC, Boulegue C, Fassler R (2011) Quantitative proteomics of the integrin adhesome show a myosin II-dependent recruitment of LIM domain proteins. EMBO Rep 12(3):259–266. https://doi.org/10.1038/embor.2011.5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kuo JC, Han X, Hsiao CT, Yates JR 3rd, Waterman CM (2011) Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for beta-Pix in negative regulation of focal adhesion maturation. Nat Cell Biol 13(4):383–393. https://doi.org/10.1038/ncb2216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Byron A, Humphries JD, Craig SE, Knight D, Humphries MJ (2012) Proteomic analysis of alpha4beta1 integrin adhesion complexes reveals alpha-subunit-dependent protein recruitment. Proteomics 12(13):2107–2114. https://doi.org/10.1002/pmic.201100487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Schiller HB, Hermann MR, Polleux J, Vignaud T, Zanivan S, Friedel CC, Sun Z, Raducanu A, Gottschalk KE, Thery M, Mann M, Fassler R (2013) Beta1- and alphav-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments. Nat Cell Biol 15(6):625–636. https://doi.org/10.1038/ncb2747

    Article  CAS  PubMed  Google Scholar 

  26. Ng DH, Humphries JD, Byron A, Millon-Fremillon A, Humphries MJ (2014) Microtubule-dependent modulation of adhesion complex composition. PLoS One 9(12):e115213. https://doi.org/10.1371/journal.pone.0115213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Byron A, Askari JA, Humphries JD, Jacquemet G, Koper EJ, Warwood S, Choi CK, Stroud MJ, Chen CS, Knight D, Humphries MJ (2015) A proteomic approach reveals integrin activation state-dependent control of microtubule cortical targeting. Nat Commun 6:6135. https://doi.org/10.1038/ncomms7135

    Article  CAS  PubMed  Google Scholar 

  28. Robertson J, Jacquemet G, Byron A, Jones MC, Warwood S, Selley JN, Knight D, Humphries JD, Humphries MJ (2015) Defining the phospho-adhesome through the phosphoproteomic analysis of integrin signalling. Nat Commun 6:6265. https://doi.org/10.1038/ncomms7265

    Article  CAS  PubMed  Google Scholar 

  29. Ajeian JN, Horton ER, Astudillo P, Byron A, Askari JA, Millon-Fremillon A, Knight D, Kimber SJ, Humphries MJ, Humphries JD (2016) Proteomic analysis of integrin-associated complexes from mesenchymal stem cells. Proteomics Clin Appl 10(1):51–57. https://doi.org/10.1002/prca.201500033

    Article  CAS  PubMed  Google Scholar 

  30. Horton ER, Byron A, Askari JA, Ng DHJ, Millon-Fremillon A, Robertson J, Koper EJ, Paul NR, Warwood S, Knight D, Humphries JD, Humphries MJ (2015) Definition of a consensus integrin adhesome and its dynamics during adhesion complex assembly and disassembly. Nat Cell Biol 17(12):1577–1587. https://doi.org/10.1038/ncb3257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Carisey A, Tsang R, Greiner AM, Nijenhuis N, Heath N, Nazgiewicz A, Kemkemer R, Derby B, Spatz J, Ballestrem C (2013) Vinculin regulates the recruitment and release of core focal adhesion proteins in a force-dependent manner. Curr Biol 23(4):271–281. https://doi.org/10.1016/j.cub.2013.01.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Iskratsch T, Yu CH, Mathur A, Liu S, Stevenin V, Dwyer J, Hone J, Ehler E, Sheetz M (2013) FHOD1 is needed for directed forces and adhesion maturation during cell spreading and migration. Dev Cell 27(5):545–559. https://doi.org/10.1016/j.devcel.2013.11.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ciobanasu C, Faivre B, Le Clainche C (2014) Actomyosin-dependent formation of the mechanosensitive talin-vinculin complex reinforces actin anchoring. Nat Commun 5:3095. https://doi.org/10.1038/ncomms4095

    Article  CAS  PubMed  Google Scholar 

  34. Yao M, Goult BT, Chen H, Cong P, Sheetz MP, Yan J (2014) Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation. Sci Rep 4:4610. https://doi.org/10.1038/srep04610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Hernandez-Varas P, Berge U, Lock JG, Stromblad S (2015) A plastic relationship between vinculin-mediated tension and adhesion complex area defines adhesion size and lifetime. Nat Commun 6:7524. https://doi.org/10.1038/ncomms8524

    Article  CAS  PubMed  Google Scholar 

  36. Haage A, Goodwin K, Whitewood A, Camp D, Bogutz A, Turner CT, Granville DJ, Lefebvre L, Plotnikov S, Goult BT, Tanentzapf G (2018) Talin autoinhibition regulates cell-ECM adhesion dynamics and wound healing in vivo. Cell Rep 25(9):2401–2416. e2405. https://doi.org/10.1016/j.celrep.2018.10.098

    Article  CAS  PubMed  Google Scholar 

  37. Chang YC, Su W, Cho EA, Zhang H, Huang Q, Philips MR, Wu J (2019) Molecular basis for autoinhibition of RIAM regulated by FAK in integrin activation. Proc Natl Acad Sci U S A 116(9):3524–3529. https://doi.org/10.1073/pnas.1818880116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Dedden D, Schumacher S, Kelley CF, Zacharias M, Biertumpfel C, Fassler R, Mizuno N (2019) The architecture of talin1 reveals an autoinhibition mechanism. Cell 179(1):120–131.e13. https://doi.org/10.1016/j.cell.2019.08.034

  39. Atherton P, Lausecker F, Carisey A, Gilmore A, Critchley D, Barsukov I, Ballestrem C (2020) Relief of talin autoinhibition triggers a force-independent association with vinculin. J Cell Biol 219(1). https://doi.org/10.1083/jcb.201903134

  40. Bachir AI, Zareno J, Moissoglu K, Plow EF, Gratton E, Horwitz AR (2014) Integrin-associated complexes form hierarchically with variable stoichiometry in nascent adhesions. Curr Biol 24(16):1845–1853. https://doi.org/10.1016/j.cub.2014.07.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hoffmann JE, Fermin Y, Stricker RL, Ickstadt K, Zamir E (2014) Symmetric exchange of multi-protein building blocks between stationary focal adhesions and the cytosol. Elife 3:e02257. https://doi.org/10.7554/eLife.02257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Han SJ, Dean KM, Whitewood J, Bachir A, Guttierrez E, Groisman A, Horwitz AR, Goult BT, Danuser G (2019) Formation of talin-vinculin pre-complexes dictates maturation of nascent adhesions by accelerated force transmission and vinculin recruitment. bioRxiv: 735183. https://doi.org/10.1101/735183

  43. Wang Y, Gilmore TD (2003) Zyxin and paxillin proteins: focal adhesion plaque LIM domain proteins go nuclear. Biochim Biophys Acta 1593(2–3):115–120. https://doi.org/10.1016/s0167-4889(02)00349-x

    Article  CAS  PubMed  Google Scholar 

  44. Hervy M, Hoffman L, Beckerle MC (2006) From the membrane to the nucleus and back again: bifunctional focal adhesion proteins. Curr Opin Cell Biol 18(5):524–532. https://doi.org/10.1016/j.ceb.2006.08.006

    Article  CAS  PubMed  Google Scholar 

  45. Byron A, Frame MC (2016) Adhesion protein networks reveal functions proximal and distal to cell-matrix contacts. Curr Opin Cell Biol 39:93–100. https://doi.org/10.1016/j.ceb.2016.02.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kleinschmidt EG, Schlaepfer DD (2017) Focal adhesion kinase signaling in unexpected places. Curr Opin Cell Biol 45:24–30. https://doi.org/10.1016/j.ceb.2017.01.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Mitra K, Carvunis AR, Ramesh SK, Ideker T (2013) Integrative approaches for finding modular structure in biological networks. Nat Rev Genet 14(10):719–732. https://doi.org/10.1038/nrg3552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Azeloglu EU, Iyengar R (2015) Signaling networks: information flow, computation, and decision making. Cold Spring Harb Perspect Biol 7(4):a005934. https://doi.org/10.1101/cshperspect.a005934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Nguyen H, Shrestha S, Tran D, Shafi A, Draghici S, Nguyen T (2019) A comprehensive survey of tools and software for active subnetwork identification. Front Genet 10:155. https://doi.org/10.3389/fgene.2019.00155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Gunsalus KC, Ge H, Schetter AJ, Goldberg DS, Han JD, Hao T, Berriz GF, Bertin N, Huang J, Chuang LS, Li N, Mani R, Hyman AA, Sonnichsen B, Echeverri CJ, Roth FP, Vidal M, Piano F (2005) Predictive models of molecular machines involved in Caenorhabditis elegans early embryogenesis. Nature 436(7052):861–865. https://doi.org/10.1038/nature03876

    Article  CAS  PubMed  Google Scholar 

  51. Goh KI, Cusick ME, Valle D, Childs B, Vidal M, Barabasi AL (2007) The human disease network. Proc Natl Acad Sci U S A 104(21):8685–8690. https://doi.org/10.1073/pnas.0701361104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Menche J, Sharma A, Kitsak M, Ghiassian SD, Vidal M, Loscalzo J, Barabasi AL (2015) Disease networks. Uncovering disease-disease relationships through the incomplete interactome. Science 347(6224):1257601. https://doi.org/10.1126/science.1257601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Tyanova S, Temu T, Cox J (2016) The MaxQuant computational platform for mass spectrometry-based shotgun proteomics. Nat Protoc 11(12):2301–2319. https://doi.org/10.1038/nprot.2016.136

    Article  CAS  PubMed  Google Scholar 

  54. Cox J, Neuhauser N, Michalski A, Scheltema RA, Olsen JV, Mann M (2011) Andromeda: a peptide search engine integrated into the MaxQuant environment. J Proteome Res 10(4):1794–1805. https://doi.org/10.1021/pr101065j

    Article  CAS  PubMed  Google Scholar 

  55. Tyanova S, Temu T, Sinitcyn P, Carlson A, Hein MY, Geiger T, Mann M, Cox J (2016) The Perseus computational platform for comprehensive analysis of (prote)omics data. Nat Methods 13(9):731–740. https://doi.org/10.1038/nmeth.3901

    Article  CAS  PubMed  Google Scholar 

  56. Chawade A, Alexandersson E, Levander F (2014) Normalyzer: a tool for rapid evaluation of normalization methods for omics data sets. J Proteome Res 13(6):3114–3120. https://doi.org/10.1021/pr401264n

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. van Buuren S, Groothuis-Oudshoorn K (2011) Mice: multivariate imputation by chained equations in R. J Stat Softw 45(3):1–67. https://doi.org/10.18637/jss.v045.i03

    Article  Google Scholar 

  58. Stark C, Breitkreutz BJ, Reguly T, Boucher L, Breitkreutz A, Tyers M (2006) BioGRID: a general repository for interaction datasets. Nucleic Acids Res 34(Database issue):D535–D539. https://doi.org/10.1093/nar/gkj109

    Article  CAS  PubMed  Google Scholar 

  59. Dittrich MT, Klau GW, Rosenwald A, Dandekar T, Muller T (2008) Identifying functional modules in protein-protein interaction networks: an integrated exact approach. Bioinformatics 24(13):i223–i231. https://doi.org/10.1093/bioinformatics/btn161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Beisser D, Klau GW, Dandekar T, Muller T, Dittrich MT (2010) BioNet: an R-package for the functional analysis of biological networks. Bioinformatics 26(8):1129–1130. https://doi.org/10.1093/bioinformatics/btq089

    Article  CAS  PubMed  Google Scholar 

  61. Csardi G, Nepusz T (2006) The igraph software package for complex network research. InterJournal Complex Syst 1695:1–9

    Google Scholar 

  62. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504. https://doi.org/10.1101/gr.1239303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Ono K, Muetze T, Kolishovski G, Shannon P, Demchak B (2015) CyREST: turbocharging cytoscape access for external tools via a RESTful API. F1000Res 4:478. https://doi.org/10.12688/f1000research.6767.1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Wang X, Shen S, Rasam SS, Qu J (2019) MS1 ion current-based quantitative proteomics: a promising solution for reliable analysis of large biological cohorts. Mass Spectrom Rev 38(6):461–482. https://doi.org/10.1002/mas.21595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Karpievitch YV, Dabney AR, Smith RD (2012) Normalization and missing value imputation for label-free LC-MS analysis. BMC Bioinformatics 13(Suppl 16):S5. https://doi.org/10.1186/1471-2105-13-S16-S5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Haukoos JS, Newgard CD (2007) Advanced statistics: missing data in clinical research—Part 1: An introduction and conceptual framework. Acad Emerg Med Off J Soc Acad Emerg Med 14(7):662–668. https://doi.org/10.1197/j.aem.2006.11.037

    Article  Google Scholar 

  67. Webb-Robertson BJ, Wiberg HK, Matzke MM, Brown JN, Wang J, McDermott JE, Smith RD, Rodland KD, Metz TO, Pounds JG, Waters KM (2015) Review, evaluation, and discussion of the challenges of missing value imputation for mass spectrometry-based label-free global proteomics. J Proteome Res 14(5):1993–2001. https://doi.org/10.1021/pr501138h

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Lazar C, Gatto L, Ferro M, Bruley C, Burger T (2016) Accounting for the multiple natures of missing values in label-free quantitative proteomics data sets to compare imputation strategies. J Proteome Res 15(4):1116–1125. https://doi.org/10.1021/acs.jproteome.5b00981

    Article  CAS  PubMed  Google Scholar 

  69. Byron A (2008) Proteomic analyses of integrin-based adhesion complexes. ProQuest Dissertations & Theses, Ann Arbor

    Google Scholar 

  70. Jeong H, Mason SP, Barabasi AL, Oltvai ZN (2001) Lethality and centrality in protein networks. Nature 411(6833):41–42. https://doi.org/10.1038/35075138

    Article  CAS  PubMed  Google Scholar 

  71. Blondel VD, Guillaume J-L, Lambiotte R, Lefebvre E (2008) Fast unfolding of communities in large networks. J Stat Mech Theory Exp 2008(10):P10008. https://doi.org/10.1088/1742-5468/2008/10/p10008

    Article  Google Scholar 

  72. Rosvall M, Bergstrom CT (2008) Maps of random walks on complex networks reveal community structure. Proc Natl Acad Sci U S A 105(4):1118–1123. https://doi.org/10.1073/pnas.0706851105

    Article  PubMed  PubMed Central  Google Scholar 

  73. Traag VA, Van Dooren P, Nesterov Y (2011) Narrow scope for resolution-limit-free community detection. Phys Rev E 84(1 Pt 2):016114. https://doi.org/10.1103/PhysRevE.84.016114

    Article  CAS  Google Scholar 

  74. Guimera R, Amaral LA (2005) Cartography of complex networks: modules and universal roles. J Stat Mech 2005(P02001):nihpa35573. https://doi.org/10.1088/1742-5468/2005/02/P02001

    Article  PubMed  Google Scholar 

  75. Guimera R, Nunes Amaral LA (2005) Functional cartography of complex metabolic networks. Nature 433(7028):895–900. https://doi.org/10.1038/nature03288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Reuter JA, Ortiz-Urda S, Kretz M, Garcia J, Scholl FA, Pasmooij AM, Cassarino D, Chang HY, Khavari PA (2009) Modeling inducible human tissue neoplasia identifies an extracellular matrix interaction network involved in cancer progression. Cancer Cell 15(6):477–488. https://doi.org/10.1016/j.ccr.2009.04.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Han JD, Bertin N, Hao T, Goldberg DS, Berriz GF, Zhang LV, Dupuy D, Walhout AJ, Cusick ME, Roth FP, Vidal M (2004) Evidence for dynamically organized modularity in the yeast protein-protein interaction network. Nature 430(6995):88–93. https://doi.org/10.1038/nature02555

    Article  CAS  PubMed  Google Scholar 

  78. Taylor IW, Linding R, Warde-Farley D, Liu Y, Pesquita C, Faria D, Bull S, Pawson T, Morris Q, Wrana JL (2009) Dynamic modularity in protein interaction networks predicts breast cancer outcome. Nat Biotechnol 27(2):199–204. https://doi.org/10.1038/nbt.1522

    Article  CAS  PubMed  Google Scholar 

  79. Chang X, Xu T, Li Y, Wang K (2013) Dynamic modular architecture of protein-protein interaction networks beyond the dichotomy of ‘date’ and ‘party’ hubs. Sci Rep 3:1691. https://doi.org/10.1038/srep01691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Willforss J, Chawade A, Levander F (2019) NormalyzerDE: online tool for improved normalization of omics expression data and high-sensitivity differential expression analysis. J Proteome Res 18(2):732–740. https://doi.org/10.1021/acs.jproteome.8b00523

    Article  CAS  PubMed  Google Scholar 

  81. Huber W, von Heydebreck A, Sultmann H, Poustka A, Vingron M (2002) Variance stabilization applied to microarray data calibration and to the quantification of differential expression. Bioinformatics 18(Suppl 1):S96–S104. https://doi.org/10.1093/bioinformatics/18.suppl_1.s96

    Article  PubMed  Google Scholar 

  82. Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK (2015) Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 43(7):e47. https://doi.org/10.1093/nar/gkv007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Templ M, Alfons A, Filzmoser P (2012) Exploring incomplete data using visualization techniques. ADAC 6(1):29–47. https://doi.org/10.1007/s11634-011-0102-y

    Article  Google Scholar 

  84. Aldecoa R, Marin I (2013) Surprise maximization reveals the community structure of complex networks. Sci Rep 3:1060. https://doi.org/10.1038/srep01060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Traag VA, Aldecoa R, Delvenne JC (2015) Detecting communities using asymptotical surprise. Phys Rev E 92(2):022816. https://doi.org/10.1103/PhysRevE.92.022816

    Article  CAS  Google Scholar 

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Acknowledgments

We thank J.D. Armstrong and C. McLean (University of Edinburgh) for discussions. A.B. was funded by Cancer Research UK (grants C157/A15703 and C157/A24837 to M.C. Frame, University of Edinburgh).

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  1. Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK

    Frederic Li Mow Chee & Adam Byron

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Correspondence to Adam Byron .

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  1. Molecular Mechanisms Program, Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Cientóficas (CSIC)-University of Salamanca, Salamanca, Spain

    Miguel Vicente-Manzanares

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Li Mow Chee, F., Byron, A. (2021). Network Analysis of Integrin Adhesion Complexes. In: Vicente-Manzanares, M. (eds) The Integrin Interactome. Methods in Molecular Biology, vol 2217. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0962-0_10

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  • DOI: https://doi.org/10.1007/978-1-0716-0962-0_10

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0961-3

  • Online ISBN: 978-1-0716-0962-0

  • eBook Packages: Springer Protocols

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