Skip to main content
Log in

Controllability and Its Applications to Biological Networks

  • Survey
  • Published:
Journal of Computer Science and Technology Aims and scope Submit manuscript

Abstract

Biological elements usually exert their functions through interactions with others to form various types of biological networks. The ability of controlling the dynamics of biological networks is of enormous benefits to pharmaceutical and medical industry as well as scientific research. Though there are many mathematical methods for steering dynamic systems towards desired states, the methods are usually not feasible for applying to complex biological networks. The difficulties come from the lack of accurate model that can capture the dynamics of interactions between biological elements and the fact that many mathematical methods are computationally intractable for large-scale networks. Recently, a concept in control theory — controllability, has been applied to investigate the dynamics of complex networks. In this article, recent advances on the controllability of complex networks and applications to biological networks are reviewed. Developing dynamic models is the prior concern for analyzing dynamics of biological networks. First, we introduce a widely used dynamic model for investigating controllability of complex networks. Then recent studies of theorems and algorithms for having complex biological networks controllable in general or specific application scenarios are reviewed. Finally, applications to real biological networks manifest that investigating the controllability of biological networks can shed lights on many critical physiological or medical problems, such as revealing biological mechanisms and identifying drug targets, from a systematic perspective.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Ito T, Chiba T, Ozawa R et al. A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proceedings of the National Academy of Sciences, 2001, 98(8): 4569-4574.

    Article  Google Scholar 

  2. Sprinzak E, Margalit H. Correlated sequence-signatures as markers of protein-protein interaction. Journal of Molecular Biology, 2001, 311(4): 681-692.

    Article  Google Scholar 

  3. Liu L Z, Wu F X, Zhang W J. Reverse engineering of gene regulatory networks from biological data. Wiley Interdisciplinary Reviews: Data Mining and Knowledge Discovery, 2012, 2(5): 365-385.

    Google Scholar 

  4. Gu S, Pasqualetti F, Cieslak M et al. Controllability of structural brain networks. Nature Communications, 2015, 6: Article No. 8414.

  5. Csermely P, Agoston V, Pongor S. The efficiency of multitarget drugs: The network approach might help drug design. Trends in Pharmacological Sciences, 2005, 26(4): 178-182.

    Article  Google Scholar 

  6. Dai Y F, Zhao X M. A survey on the computational approaches to identify drug targets in the postgenomic era. BioMed Research International, 2015, 2015: Article No. 239654.

  7. Wang X, Gulbahce N, Yu H. Network-based methods for human disease gene prediction. Briefings in Functional Genomics, 2011, 10(5): 280-293.

    Article  Google Scholar 

  8. Chen B, Fan W, Liu J et al. Identifying protein complexes and functional modules — From static PPI networks to dynamic PPI networks. Briefings in Bioinformatics, 2013, 15(2): 177-194.

    Article  Google Scholar 

  9. Kalman R E. Mathematical description of linear dynamical systems. Journal of the Society for Industrial and Applied Mathematics Control, Series A, 1963, 1(2): 152-192.

    Article  MathSciNet  MATH  Google Scholar 

  10. Lin C T. Structural controllability. IEEE Transactions on Automatic Control, 1974, 19(3): 201-208.

    Article  MathSciNet  MATH  Google Scholar 

  11. Liu Y Y, Slotine J J, Barabási A L. Controllability of complex networks. Nature, 2011, 473(7346): 167-173.

    Article  Google Scholar 

  12. Wang B, Gao L, Zhang Q et al. Diversified control paths: A significant way disease genes perturb the human regulatory network. PLoS One, 2015, 10(8): Article No. e0135491.

  13. Wu L, Shen Y, Li M et al. Network output controllabilitybased method for drug target identification. IEEE Transactions on Nano Bioscience, 2015, 14(2): 184-191.

    Article  Google Scholar 

  14. Yan G, Vértes P E, Towlson E K et al. Network control principles predict neuron function in the caenorhabditis elegans connectome. Nature, 2017, 550(7677): 519-523.

    Article  Google Scholar 

  15. D’haeseleer P, Wen X, Fuhrman S et al. Linear modeling of mRNA expression levels during CNS development and injury. Pacific Symposium on Biocomputing, 1999, 4: 41-52.

    Google Scholar 

  16. Slotine J J, Li W. Applied Nonlinear Control. Pearson, 1991.

  17. Liu Y Y, Barabási A L. Control principles of complex systems. Reviews of Modern Physics, 2016, 88(3): Article 035006.

  18. Shields R, Pearson J. Structural controllability of multiinput linear systems. IEEE Transactions on Automatic Control, 1976, 21(2): 203-212.

    Article  MathSciNet  MATH  Google Scholar 

  19. Glover K, Silverman L. Characterization of structural controllability. IEEE Transactions on Automatic Control, 1976, 21(4): 534-537.

    Article  MathSciNet  MATH  Google Scholar 

  20. Hosoe S, Matsumoto K. On the irreducibility condition in the structural controllability theorem. IEEE Transactions on Automatic Control, 1979, 24(6): 963-966.

    Article  MathSciNet  MATH  Google Scholar 

  21. Linnemann A. A further simplification in the proof of the structural controllability theorem. IEEE Transactions on Automatic Control, 1986, 31(7): 638-639.

    Article  MathSciNet  MATH  Google Scholar 

  22. Hosoe S. Determination of generic dimensions of controllable subspaces and its application. IEEE Transactions on Automatic Control, 1980, 25(6): 1192-1196.

    Article  MathSciNet  MATH  Google Scholar 

  23. Poljak S. On the generic dimension of controllable subspaces. IEEE Transactions on Automatic Control, 1990, 35(3): 367-369.

    Article  MathSciNet  MATH  Google Scholar 

  24. Murota K, Poljak S. Note on a graph-theoretic criterion for structural output controllability. IEEE Transactions on Automatic Control, 1990, 35(8): 939-942.

    Article  MathSciNet  MATH  Google Scholar 

  25. Wu F X,Wu L,Wang J et al. Transittability of complex networks and its applications to regulatory biomolecular networks. Scientific Reports, 2014, 4: Article No. 4819.

  26. Mayeda H, Yamada T. Strong structural controllability. SIAM Journal on Control and Optimization, 1979, 17(1): 123-138.

    Article  MathSciNet  MATH  Google Scholar 

  27. Tu C. Strong structural control centrality of a complex network. Physica Scripta, 2015, 90(3): Article No. 035202.

  28. Nepusz T, Vicsek T. Controlling edge dynamics in complex networks. Nature Physics, 2012, 8(7): 568-573.

    Article  Google Scholar 

  29. Cowan N J, Chastain E J, Vilhena D A et al. Nodal dynamics, not degree distributions, determine the structural controllability of complex networks. PLoS One, 2012, 7(6): Article No. e38398.

  30. Nie S, Wang X, Zhang H et al. Robustness of controllability for networks based on edge-attack. PLoS One, 2014, 9(2): Article No. e89066.

  31. Wang W X, Ni X, Lai Y C et al. Optimizing controllability of complex networks by minimum structural perturbations. Physical Review E, 2012, 85(2): Article No. 026115.

  32. Wu L, Li M, Wang J et al. CytoCtrlAnalyser: A cytoscape app for biomolecular network controllability analysis. Bioinformatics, 2018, 34(8): 1428-1430.

    Article  Google Scholar 

  33. Wu L, Li M, Wang J et al. Minimum steering node set of complex networks and its applications to biomolecular networks. IET Systems Biology, 2016, 10(3): 116-123.

    Article  Google Scholar 

  34. Liu Y Y, Slotine J J, Barab´asi A L. Control centrality and hierarchical structure in complex networks. PLoS One, 2012, 7(9): Article No. e44459.

  35. Iudice F L, Garofalo F, Sorrentino F. Structural permeability of complex networks to control signals. Nature Communications, 2015, 6: Article No. 8349.

  36. Liu X, Pan L. Controllability of the better chosen partial networks. Physica A: Statistical Mechanics and Its Applications, 2016, 456: 120-127.

    Article  MathSciNet  MATH  Google Scholar 

  37. Commault C, van der Woude J, Boukhobza T. On the fixed controllable subspace in linear structured systems. Systems & Control Letters, 2017, 102: 42-47.

    Article  MathSciNet  MATH  Google Scholar 

  38. Wu L, Shen Y, Li M et al. Drug target identification based on structural output controllability of complex networks. In Proc. the 10th International Symposium Bioinformatics Research and Applications, June 2014, pp.188-199.

  39. Gao J, Liu Y Y, D’Souza R M et al. Target control of complex networks. Nature Communications, 2014, 5: Article No. 5415.

  40. Ogata K. Modern Control Engineering (3rd edition). Prentice Hall, 1996.

  41. Hopcroft J E, Karp R M. An n5/2 algorithm for maximum matchings in bipartite graphs. SIAM Journal on Computing, 1973, 2(4): 225-231.

    Article  MathSciNet  MATH  Google Scholar 

  42. Zhang X, Lv T, Yang X et al. Structural controllability of complex networks based on preferential matching. PLoS One, 2014, 9(11): Article No. e112039.

  43. Goodrich M T, Tamassia R. Algorithm Design: Foundation, Analysis and Internet Examples. John Wiley & Sons, 2006.

  44. Wu L, Tang L, Li M et al. The MSS of complex networks with centrality based preference and its application to biomolecular networks. In Proc. the 2016 IEEE International Conference on Bioinformatics and Biomedicine, December 2016, pp.229-234.

  45. Pequito S, Kar S, Aguiar A P. On the complexity of the constrained input selection problem for structural linear systems. Automatica, 2015, 62: 193-199.

    Article  MathSciNet  MATH  Google Scholar 

  46. Lindmark G, Altafini C. Controllability of complex networks with unilateral inputs. Scientific Reports, 2017, 7: Article No. 1824.

  47. Rugh W J, Kailath T. Linear System Theory (2nd edition). Pearson, 1995.

  48. Wang L Z, Chen Y Z, Wang W X et al. Physical controllability of complex networks. Scientific Reports, 2017, 7: Article No. 40198.

  49. Li G, Tang P, Wen C et al. Boundary constraints for minimum cost control of directed networks. IEEE Transactions on Cybernetics, 2017, 47(12): 4196-4207.

    Article  Google Scholar 

  50. Czeizler E, Gratie C, Chiu W K et al. Target controllability of linear networks. In Proc. the 14th International Conference on Computational Methods in Systems Biology, September 2016, pp.67-81.

  51. Kuhn H W. The Hungarian method for the assignment problem. Naval Research Logistics Quarterly, 1955, 2(1/2): 83-97.

    Article  MathSciNet  MATH  Google Scholar 

  52. Zhang X, Wang H, Lv T. Efficient target control of complex networks based on preferential matching. PLoS One, 2017, 12(4): Article No. e0175375.

  53. Liu X, Pan L, Stanley H E et al. Controllability of giant connected components in a directed network. Physical Review E, 2017, 95(4): Article No. 042318.

  54. Piao X, Lv T, Zhang X et al. Strategy for community control of complex networks. Physica A: Statistical Mechanics and Its Applications, 2015, 421: 98-108.

    Article  Google Scholar 

  55. Guo W F, Zhang S W, Wei Z G et al. Constrained target controllability of complex networks. Journal of Statistical Mechanics: Theory and Experiment, 2017, 2017(6): Article No. 063402.

  56. Khazanchi R, Dempsey K, Thapa I et al. On identifying and analyzing significant nodes in protein-protein interaction networks. In Proc. the 23rd IEEE International Conference on Data Mining Workshops, December 2013, pp.343-348.

  57. Badhwar R, Bagler G. Control of neuronal network in caenorhabditis elegans. PLoS One, 2015, 10(9): Article No. e0139204.

  58. Noori H R, Schöttler J, Ercsey-Ravasz M et al. A multiscale cerebral neurochemical connectome of the rat brain. PLoS Biology, 2017, 15(7): Article No. e2002612.

  59. Deisseroth K. Circuit dynamics of adaptive and maladaptive behaviour. Nature, 2014, 505(7483): 309-317.

    Article  Google Scholar 

  60. Kringelbach M L, Jenkinson N, Owen S L et al. Translational principles of deep brain stimulation. Nature Reviews Neuroscience, 2007, 8(8): 623-635.

    Article  Google Scholar 

  61. Li F, Long T, Lu Y et al. The yeast cell-cycle network is robustly designed. Proceedings of the National Academy of Sciences of the United States of America, 2004, 101(14): 4781-4786.

    Article  Google Scholar 

  62. Davidich M I, Bornholdt S. Boolean network model predicts cell cycle sequence of fission yeast. PLoS One, 2008, 3(2): Article No. e1672.

  63. Moes M, Le Béchec A, Crespo I et al. A novel network integrating a miRNA-203/SNAI1 feedback loop which regulates epithelial to mesenchymal transition. PLoS One, 2012, 7(4): Article No. e35440.

  64. Krumsiek J, Marr C, Schroeder T et al. Hierarchical differentiation of myeloid progenitors is encoded in the transcription factor network. PLoS One, 2011, 6(8): Article No. e22649.

  65. Mendoza L. A network model for the control of the differentiation process in Th cells. Biosystems, 2006, 84(2): 101-114.

    Article  Google Scholar 

  66. Lee H J, Takemoto N, Kurata H et al. Gata-3 induces T helper cell type 2 (Th2) cytokine expression and chromatin remodeling in committed Th1 cells. Journal of Experimental Medicine, 2000, 192(1): 105-116.

    Article  Google Scholar 

  67. Szabo S J, Kim S T, Costa G L et al. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell, 2000, 100(6): 655-669.

    Article  Google Scholar 

  68. Hwang E S, Szabo S J, Schwartzberg P L et al. T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science, 2005, 307(5708): 430-433.

    Article  Google Scholar 

  69. Kanhaiya K, Czeizler E, Gratie C et al. Controlling directed protein interaction networks in cancer. Technical Report, Turku Centre for Computer Science, 2017. http://tucs.fi/publications/attachment.php?fname=tKaCzGrPe16a.full.pdf, Nov. 2018.

  70. Wu L, Tang L, Li M et al. Biomolecular network controllability with drug binding information. IEEE Transactions on Nano Bioscience, 2017, 16(5): 326-332.

    Article  Google Scholar 

  71. Jia T, Liu Y Y, Csóka E et al. Emergence of bimodality in controlling complex networks. Nature Communications, 2013, 4: Article No. 2002.

  72. Liu X, Pan L. Identifying driver nodes in the human signaling network using structural controllability analysis. IEEE/ACM Transactions on Computational Biology and Bioinformatics, 2015, 12(2): 467-472.

    Article  Google Scholar 

  73. Jia T, Barabási A L. Control capacity and a random sampling method in exploring controllability of complex networks. Scientific Reports, 2013, 3: Article No. 2354.

  74. Liu X, Pan L. Detection of driver metabolites in the human liver metabolic network using structural controllability analysis. BMC Systems Biology, 2014, 8(1): Article No. 51.

  75. Vinayagam A, Gibson T E, Lee H J et al. Controllability analysis of the directed human protein interaction network identifies disease genes and drug targets. Proceedings of the National Academy of Sciences of the United States of America, 2016, 113(18): 4976-4981.

    Article  Google Scholar 

  76. Matsuoka Y, Matsumae H, Katoh M et al. A comprehensive map of the influenza A virus replication cycle. BMC Systems Biology, 2013, 7(1): Article No. 97.

  77. Uhart M, Flores G, Bustos D. M. Controllability of proteinprotein interaction phosphorylation-based networks: Participation of the hub 14-3-3 protein family. Scientific Reports, 2016, 6: Article No. 26234.

  78. Ravindran V, Sunitha V, Bagler G. Identification of critical regulatory genes in cancer signaling network using controllability analysis. Physica A: Statistical Mechanics and Its Applications, 2017, 474: 134-143.

    Article  Google Scholar 

  79. Ruths J, Ruths D. Control profiles of complex networks. Science, 2014, 343(6177): 1373-1376.

    Article  MathSciNet  MATH  Google Scholar 

  80. Tu C, Rocha R P, Corbetta M et al. Warnings and caveats in brain controllability. Neuroimage, 2017, 176: 83-91.

    Article  Google Scholar 

  81. Vanunu O, Magger O, Ruppin E et al. Associating genes and protein complexes with disease via network propagation. PLoS Computational Biology, 2010, 6(1): Article No. e1000641.

  82. Wang B, Gao L, Gao Y. Control range: A controllabilitybased index for node significance in directed networks. Journal of Statistical Mechanics: Theory and Experiment, 2012, 2012(04): Article No. P04011.

  83. Wang B, Gao L, Gao Y et al. Controllability and observability analysis for vertex domination centrality in directed networks. Scientific Reports, 2014, 4: Article No. 5399.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fang-Xiang Wu.

Electronic supplementary material

ESM 1

(PDF 124 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, L., Li, M., Wang, JX. et al. Controllability and Its Applications to Biological Networks. J. Comput. Sci. Technol. 34, 16–34 (2019). https://doi.org/10.1007/s11390-019-1896-x

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11390-019-1896-x

Keywords

Navigation