Skip to main content
SpringerLink
Log in

Case Studies

  • Chapter
  • First Online:
Modeling Methods for Medical Systems Biology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1069))

  • 832 Accesses

Abstract

The aim of this chapter is to illustrate the modeling procedures discussed in the previous chapter via three well-chosen examples.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Aberg, K. M., Man, M. Q., Gallo, R. L., Ganz, T., Crumrine, D., Brown, B. E., et al. (2008). Co-regulation and interdependence of the mammalian epidermal permeability and antimicrobial barriers. Journal of Investigative Dermatology, 128(4), 917–925.

    Article  CAS  Google Scholar 

  2. Abou-Jaoudé, W., Monteiro, P. T., Naldi, A., Grandclaudon, M., Soumelis, V., Chaouiya, C., et al. (2015). Model checking to assess T-helper cell plasticity. Frontiers in Bioengineering and Biotechnology, 2, 86.

    PubMed  PubMed Central  Google Scholar 

  3. Albert, R., & Barabási, A. L. (2002). Statistical mechanics of complex networks. Reviews of Modern Physics, 74(1), 47.

    Article  Google Scholar 

  4. Aliahmadi, E., Gramlich, R., Grützkau, A., Hitzler, M., Krüger, M., Baumgrass, R., et al. (2009). TLR2-activated human Langerhans cells promote Th17 polarization via IL-1β, TGF-β and IL-23. European Journal of Immunology, 39(5), 1221–1230.

    Article  PubMed  CAS  Google Scholar 

  5. Altrock, P. M., Liu, L. L., & Michor, F. (2015). The mathematics of cancer: Integrating quantitative models. Nature Reviews Cancer, 15(12), 730–745.

    Article  PubMed  CAS  Google Scholar 

  6. Álvarez-Buylla, E. R., Azpeitia, E., Barrio, R., Benítez, M., & Padilla-Longoria, P. (2010). From ABC genes to regulatory networks, epigenetic landscapes and flower morphogenesis: Making biological sense of theoretical approaches. Seminars in Cell & Developmental Biology, 21(1), 108–117.

    Article  Google Scholar 

  7. Álvarez-Buylla, E. R., Benítez, M., Davila, E. B., Chaos, A., Espinosa-Soto, C., & Padilla-Longoria, P. (2007). Gene regulatory network models for plant development. Current Opinion in Plant Biology, 10(1), 83–91.

    Article  PubMed  Google Scholar 

  8. Álvarez-Buylla, E. R., Chaos, Á., Aldana, M., Benítez, M., Cortes-Poza, Y., Espinosa-Soto, C., et al. (2008). Floral morphogenesis: Stochastic explorations of a gene network epigenetic landscape. PLoS One, 3(11), e3626.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Álvarez-Buylla, E. R., Dávila-Velderrain, J., & Martínez-García, J. C. (2016). Systems biology approaches to development beyond bioinformatics: Nonlinear mechanistic models using plant systems. BioScience, 66(5), 371–383.

    Article  Google Scholar 

  10. Anand, P., Kunnumakara, A. B., Sundaram, C., Harikumar, K. B., Tharakan, S. T., Lai, O. S., et al. (2008). Cancer is a preventable disease that requires major lifestyle changes. Pharmaceutical Research, 25(9), 2097–2116.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Antebi, Y. E., Nandagopal, N., & Elowitz, M. B. (2017). An operational view of intercellular signaling pathways. Current Opinion in Systems Biology, 1, 16–24.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Ao, P., Galas, D., Hood, L., & Zhu, X. (2008). Cancer as robust intrinsic state of endogenous molecular-cellular network shaped by evolution. Medical Hypotheses, 70(3), 678–684.

    Article  PubMed  CAS  Google Scholar 

  13. Azpeitia, E., Benítez, M., Padilla-Longoria, P., Espinosa-Soto, C., & Álvarez-Buylla, E. R. (2011). Dynamic network-based epistasis analysis: Boolean examples. Frontiers in Plant Science, 2, 92.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Azpeitia, E., Benítez, M., Vega, I., Villarreal, C., & Álvarez-buylla, E. R. (2010). Single-cell and coupled GRN models of cell patterning in the Arabidopsis thaliana root stem cell niche. BMC Systems Biology, 4, 134.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Azpeitia, E., Muñoz, S., González-Tokman, D., Martínez-Sánchez, M. E., Weinstein, N., Naldi, A., et al. (2017). The combination of the functionalities of feedback circuits is determinant for the attractors’ number and size in pathway-like Boolean networks. Scientific Reports, 7, 42023.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Bäckman, A., Ny, A., Edlund, M., Ekholm, E., Hammarström, B. E., Törnell, J., et al. (2002). Epidermal overexpression of stratum corneum chymotryptic enzyme in mice: A model for chronic itchy dermatitis. Journal of Investigative Dermatology, 118(3), 444–449.

    Article  Google Scholar 

  17. Baker, B. S. (2006). The role of microorganisms in atopic dermatitis. Clinical & Experimental Immunology, 144(1), 1–9.

    Article  CAS  Google Scholar 

  18. Balkwill, F., & Mantovani, A. (2001). Inflammation and cancer: Back to Virchow? The Lancet, 357(9255), 539–545.

    Article  CAS  Google Scholar 

  19. Balleza, E., Alvarez-Buylla, E. R., Chaos, A., Kauffman, S., Shmulevich, I., & Aldana, M. (2008). Critical dynamics in genetic regulatory networks: Examples from four kingdoms. PLoS One, 3(6), e2456.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Battula, V. L., Evans, K. W., Hollier, B. G., Shi, Y., Marini, F. C., Ayyanan, A., et al. (2010). Epithelial-mesenchymal transition-derived cells exhibit multilineage differentiation potential similar to mesenchymal stem cells. Stem Cells, 28(8), 1435–1445.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Benítez, M., Espinosa-Soto, C., Padilla-Longoria, P., Díaz, J., & Álvarez-Buylla, E. R. (2007). Equivalent genetic regulatory networks in different contexts recover contrasting spatial cell patterns that resemble those in Arabidopsis root and leaf epidermis: A dynamic model. The International Journal of Developmental Biology, 51, 139–155.

    Article  PubMed  CAS  Google Scholar 

  22. Ben-Porath, I., Thomson, M. W., Carey, V. J., Ge, R., Bell, G. W., Regev, A., et al. (2008). An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nature Genetics, 40(5), 499–507.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Bernard, F. X., Morel, F., Camus, M., Pedretti, N., Barrault, C., Garnier, J., et al. (2012). Keratinocytes under fire of proinflammatory cytokines: Bona fide innate immune cells involved in the physiopathology of chronic atopic dermatitis and psoriasis. Journal of Allergy, 2012, 10. Article ID 718725.

    Google Scholar 

  24. Bluestone, J. A., Mackay, C. R., O’shea, J. J., & Stockinger, B. (2009). The functional plasticity of T cell subsets. Nature Reviews Immunology, 9(11), 811–816.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Bonelli, M., Shih, H. Y., Hirahara, K., Singelton, K., Laurence, A., Poholek, A., et al. (2014). Helper T cell plasticity: Impact of extrinsic and intrinsic signals on transcriptomes and epigenomes. In Transcriptional control of lineage differentiation in immune cells (pp. 279–326). Berlin: Springer International Publishing.

    Google Scholar 

  26. Boveri, T. (1914). The origin of malignant tumors (M. Boveri (1929) Baillière, Tindall & Cox, Trans.). Baltimore: The Williams and Wilkins Company.

    Google Scholar 

  27. Brattsand, M., Stefansson, K., Lundh, C., Haasum, Y., & Egelrud, T. (2005). A proteolytic cascade of kallikreins in the stratum corneum. Journal of Investigative Dermatology, 124(1), 198–203.

    Article  CAS  Google Scholar 

  28. Breitfeld, D., Ohl, L., Kremmer, E., Ellwart, J., Sallusto, F., Lipp, M., et al. (2000). Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. Journal of Experimental Medicine, 192(11), 1545–1552.

    Article  CAS  Google Scholar 

  29. Briot, A., Deraison, C., Lacroix, M., Bonnart, C., Robin, A., Besson, C., et al. (2009). Kallikrein 5 induces atopic dermatitis-like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome. Journal of Experimental Medicine, 206(5), 1135–1147.

    Article  CAS  Google Scholar 

  30. Brown, S. J., Kroboth, K., Sandilands, A., Campbell, L. E., Pohler, E., Kezic, S., et al. (2012). Intragenic copy number variation within filaggrin contributes to the risk of atopic dermatitis with a dose-dependent effect. Journal of Investigative Dermatology, 132(1), 98–104.

    Article  CAS  Google Scholar 

  31. Buddenkotte, J., Stroh, C., Engels, I. H., Moormann, C., Shpacovitch, V. M., Seeliger, S., et al. (2005). Agonists of proteinase-activated receptor-2 stimulate upregulation of intercellular cell adhesion molecule-1 in primary human keratinocytes via activation of NF-κB. Journal of Investigative Dermatology, 124(1), 38–45.

    Article  CAS  Google Scholar 

  32. Campisi, J., Andersen, J. K., Kapahi, P., & Melov, S. (2011). Cellular senescence: A link between cancer and age-related degenerative disease? Seminars in Cancer Biology, 21(6), 354–359.

    PubMed  PubMed Central  CAS  Google Scholar 

  33. Cannons, J. L., Lu, K. T., & Schwartzberg, P. L. (2013). T follicular helper cell diversity and plasticity. Trends in Immunology, 34(5), 200–207.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Caubet, C., Jonca, N., Brattsand, M., Guerrin, M., Bernard, D., Schmidt, R., et al. (2004). Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7. Journal of Investigative Dermatology, 122(5), 1235–1244.

    Article  CAS  Google Scholar 

  35. Chen, C., & Wang, J. (2016). A physical mechanism of cancer heterogeneity. Scientific Reports, 6, 20679.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Choi, M., Shi, J., Jung, S. H., Chen, X., & Cho, K. H. (2012). Attractor landscape analysis reveals feedback loops in the p53 network that control the cellular response to DNA damage. Science Signaling, 5(251), ra83.

    Google Scholar 

  37. Christodoulides, P., Hirata, Y., Domínguez-Hüttinger, E., Danby, S. G., Cork, M. J., Williams, H. C., et al. (2017). Computational design of treatment strategies for proactive therapy on atopic dermatitis using optimal control theory. Philosophical Transactions of the Royal Society A, 375(2096), 20160285.

    Article  CAS  Google Scholar 

  38. Ciofani, M., Madar, A., Galan, C., Sellars, M., Mace, K., Pauli, F., et al. (2012). A validated regulatory network for Th17 cell specification. Cell, 151(2), 289–303.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Clark, W. H. (1995). The nature of cancer: Morphogenesis and progressive (self)-disorganization in neoplastic development and progression. Acta Oncologica, 34(1), 3–21.

    Article  PubMed  Google Scholar 

  40. Cookson, W. (2004). The immunogenetics of asthma and eczema: A new focus on the epithelium. Nature Reviews Immunology, 4(12), 978–988.

    Article  PubMed  CAS  Google Scholar 

  41. Coppé, J. P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., et al. (2008). Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biology, 6(12), e301.

    Article  PubMed Central  CAS  Google Scholar 

  42. Cork, M. J., Danby, S. G., Vasilopoulos, Y., Hadgraft, J., Lane, M. E., Moustafa, M., et al. (2009). Epidermal barrier dysfunction in atopic dermatitis. Journal of Investigative Dermatology, 129(8), 1892–1908.

    Article  CAS  Google Scholar 

  43. Cork, M. J., Robinson, D. A., Vasilopoulos, Y., Ferguson, A., Moustafa, M., MacGowan, A., et al. (2006). New perspectives on epidermal barrier dysfunction in atopic dermatitis: Gene–environment interactions. Journal of Allergy and Clinical Immunology, 118(1), 3–21.

    Article  CAS  Google Scholar 

  44. Creixell, P., Schoof, E. M., Erler, J. T., & Linding, R. (2012). Navigating cancer network attractors for tumor-specific therapy. Nature Biotechnology, 30(9), 842–848.

    Article  PubMed  CAS  Google Scholar 

  45. Crotty, S. (2011). Follicular helper CD4 T cells (Tfh). Annual Review of Immunology, 29, 621–663.

    Article  PubMed  CAS  Google Scholar 

  46. Cruickshanks, H. A., McBryan, T., Nelson, D. M., VanderKraats, N. D., Shah, P. P., Van Tuyn, J., et al. (2013). Senescent cells harbour features of the cancer epigenome. Nature Cell Biology, 15(12), 1495–1506.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Csermely, P., & Korcsmáros, T. (2013). Cancer-related networks: A help to understand, predict and change malignant transformation. Seminars in Cancer Biology, 23(4), 209–212.

    Article  PubMed  CAS  Google Scholar 

  48. Dai, L., Korolev, K. S., & Gore, J. (2013). Slower recovery in space before collapse of connected populations. Nature, 496(7445), 355–358.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Danby, S. G., Chittock, J., Brown, K., Albenali, L. H., & Cork, M. J. (2014). The effect of tacrolimus compared with betamethasone valerate on the skin barrier in volunteers with quiescent atopic dermatitis. British Journal of Dermatology, 170(4), 914–921.

    Article  CAS  Google Scholar 

  50. Das, J., Chen, C. H., Yang, L., Cohn, L., Ray, P., & Ray, A. (2001). A critical role for NF-κB in GATA3 expression and TH2 differentiation in allergic airway inflammation. Nature Immunology, 2(1), 45–50.

    Article  PubMed  CAS  Google Scholar 

  51. Davila-Velderrain, J., & Álvarez-Buylla, E. R. (2014). Bridging genotype and phenotype. In Frontiers in ecology, evolution and complexity (pp. 144–154). Mexico: EditoraC3 CopIt-arXives, UNAM.

    Google Scholar 

  52. Davila-Velderrain, J., Juarez-Ramiro, L., Martinez-Garcia, J. C., Alvarez-Buylla, E. R. (2015). Methods for characterizing the epigenetic attractors landscape associated with Boolean gene regulatory networks. arXiv preprint. arXiv:1510.04230.

    Google Scholar 

  53. Davila-Velderrain, J., Villarreal, C., & Álvarez-Buylla, E. R. (2015). Reshaping the epigenetic landscape during early flower development: Induction of attractor transitions by relative differences in gene decay rates. BMC Systems Biology, 9(1), 20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. De Benedetto, A., Kubo, A., & Beck, L. A. (2012). Skin barrier disruption: A requirement for allergen sensitization? Journal of Investigative Dermatology, 132(3), 949–963.

    Article  CAS  Google Scholar 

  55. De Craene, B., & Berx, G. (2013). Regulatory networks defining EMT during cancer initiation and progression. Nature Reviews Cancer, 13(2), 97–110.

    Article  PubMed  CAS  Google Scholar 

  56. de Luis Balaguer, M. A., Fisher, A. P., Clark, N. M., Fernandez-Espinosa, M. G., Moller, B., Weijers, D., et al. (2017). An inference approach combines spatial and temporal gene expression data to predict gene regulatory networks in Arabidopsis stem cells. bioRxiv, 140269.

    Google Scholar 

  57. Demerjian, M., Hachem, J. P., Tschachler, E., Denecker, G., Declercq, W., Vandenabeele, P., et al. (2008). Acute modulations in permeability barrier function regulate epidermal cornification: Role of caspase-14 and the protease-activated receptor type 2. The American Journal of Pathology, 172(1), 86–97.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Deraison, C., Bonnart, C., Lopez, F., Besson, C., Robinson, R., Jayakumar, A., et al. (2007). LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction. Molecular Biology of the Cell, 18(9), 3607–3619.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Domínguez Hüttinger, E. (2014). Mathematical modelling of epithelium homeostasis (Doctoral dissertation, Imperial College London).

    Google Scholar 

  60. Dominguez-Hüttinger, E., Boon, N. J., Clarke, T. B., & Tanaka, R. J. (2017). Mathematical modelling of colonization, invasive infection and treatment of Streptococcus pneumoniae. Frontiers in Physiology, 8, 115.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Domínguez-Hüttinger, E., Christodoulides, P., Miyauchi, K., Irvine, A. D., Okada-Hatakeyama, M., Kubo, M., et al. (2017). Mathematical modeling of atopic dermatitis reveals “double-switch” mechanisms underlying 4 common disease phenotypes. Journal of Allergy and Clinical Immunology, 139(6), 1861–1872.

    Article  Google Scholar 

  62. Domínguez-Hüttinger, E., Ono, M., Barahona, M., & Tanaka, R. J. (2013). Risk factor-dependent dynamics of atopic dermatitis: Modelling multi-scale regulation of epithelium homeostasis. Interface Focus, 3(2), 20120090.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Dommisch, H., Chung, W. O., Rohani, M. G., Williams, D., Rangarajan, M., Curtis, M. A., et al. (2007). Protease-activated receptor 2 mediates human beta-defensin 2 and CC chemokine ligand 20 mRNA expression in response to proteases secreted by Porphyromonas gingivalis. Infection and Immunity, 75(9), 4326–4333.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Duhen, T., Duhen, R., Lanzavecchia, A., Sallusto, F., & Campbell, D. J. (2012). Functionally distinct subsets of human FOXP3+ Treg cells that phenotypically mirror effector Th cells. Blood, 119(19), 4430–4440.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. DuPage, M., & Bluestone, J. A. (2016). Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease. Nature Reviews Immunology, 16(3), 149–163.

    Article  PubMed  CAS  Google Scholar 

  66. Ehlken, B., Mḧrenschlager, M., Kugland, B., Berger, K., Quednau, K., & Ring, J. (2005). Cost-of-illness study in patients suffering from atopic eczema in Germany. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete, 56(12), 1144–1151.

    Google Scholar 

  67. Elias, P. M., Ahn, S. K., Denda, M., Brown, B. E., Crumrine, D., Kimutai, L. K., et al. (2002). Modulations in epidermal calcium regulate the expression of differentiation-specific markers. Journal of Investigative Dermatology, 119(5), 1128–1136.

    Article  CAS  Google Scholar 

  68. Elias, P. M., Brown, B. E., Crumrine, D., Feingold, K. R., & Ahn, S. K. (2002). Origin of the epidermal calcium gradient: Regulation by barrier status and role of active vs passive mechanisms. Journal of Investigative Dermatology, 119(6), 1269–1274.

    Article  CAS  Google Scholar 

  69. Elias, P. M., & Schmuth, M. (2009). Abnormal skin barrier in the etiopathogenesis of atopic dermatitis. Current Allergy and Asthma Reports, 9(4), 265–272.

    Article  PubMed  CAS  Google Scholar 

  70. Elias, P. M., & Wakefield, J. S. (2011). Therapeutic implications of a barrier-based pathogenesis of atopic dermatitis. Clinical Reviews in Allergy & Immunology, 41(3), 282–295.

    Article  CAS  Google Scholar 

  71. Ellis, C. N., Drake, L. A., Prendergast, M. M., Abramovits, W., Boguniewicz, M., Daniel, C. R., et al. (2002). Cost of atopic dermatitis and eczema in the United States. Journal of the American Academy of Dermatology, 46(3), 361–370.

    Article  PubMed  Google Scholar 

  72. Ellmeier, W., & Taniuchi, I. (Eds.). (2014). Transcriptional control of lineage differentiation in immune cells (Vol. 381). Berlin: Springer.

    Google Scholar 

  73. Enciso, J., Álvarez-Buylla, E., & Pelayo, R. (2017). A multi-modular Boolean network for the study of acute lymphoblastic leukemia. Experimental Hematology, 53, S109.

    Article  Google Scholar 

  74. Espinosa-Soto, C., Padilla-Longoria, P., & Álvarez-Buylla, E. R. (2004). A gene regulatory network model for cell–fate determination during Arabidopsis thaliana flower development that is robust and recovers experimental gene expression profiles. Plant Cell, 16, 2923–2939.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Ewald, J. A., Desotelle, J. A., Wilding, G., & Jarrard, D. F. (2010). Therapy-induced senescence in cancer. Journal of the National Cancer Institute, 102(20), 1536–1546.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Fallon, P. G., Sasaki, T., Sandilands, A., Campbell, L. E., Saunders, S. P., Mangan, N. E., et al. (2009). A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming. Nature Genetics, 41(5), 602–608.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Feinberg, A. P., Koldobskiy, M. A., & Göndör, A. (2016). Epigenetic modulators, modifiers and mediators in cancer aetiology and progression. Nature Reviews Genetics, 17(5), 284–299.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Foo, J., Leder, K., & Michor, F. (2011). Stochastic dynamics of cancer initiation. Physical Biology, 8(1), 015002.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Fortugno, P., Furio, L., Teson, M., Berretti, M., El Hachem, M., Zambruno, G., et al. (2012). The 420K LEKTI variant alters LEKTI proteolytic activation and results in protease deregulation: Implications for atopic dermatitis. Human Molecular Genetics, 21(19), 4187–4200.

    Article  PubMed  CAS  Google Scholar 

  80. Friend, S. H., Dryja, T. P., & Weinberg, R. A. (1988). Oncogenes and tumor-suppressing genes. New England Journal of Medicine, 318(10), 618–622.

    Article  CAS  Google Scholar 

  81. Fry, L. (2003). An atlas of atopic eczema. Boca Raton: Parthenon.

    Book  Google Scholar 

  82. Galic, S., Sachithanandan, N., Kay, T. W., & Steinberg, G. R. (2014). Suppressor of cytokine signalling (SOCS) proteins as guardians of inflammatory responses critical for regulating insulin sensitivity. Biochemical Journal, 461(2), 177–188.

    Article  CAS  Google Scholar 

  83. Galli, S. J., Tsai, M., & Piliponsky, A. M. (2008). The development of allergic inflammation. Nature, 454(7203), 445–454.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Garbe, J. C., Vrba, L., Sputova, K., Fuchs, L., Novak, P., Brothman, A. R., et al. (2014). Immortalization of normal human mammary epithelial cells in two steps by direct targeting of senescence barriers does not require gross genomic alterations. Cell Cycle, 13(21), 3423–3435.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Garraway, L. A., & Lander, E. S. (2013). Lessons from the cancer genome. Cell, 153(1), 17–37.

    Article  PubMed  CAS  Google Scholar 

  86. Geginat, J., Paroni, M., Facciotti, F., Gruarin, P., Kastirr, I., Caprioli, F., et al. (2013). The CD4-centered universe of human T cell subsets. Seminars in Immunology, 25(4), 252–262. New York: Academic.

    Google Scholar 

  87. Gene Ontology Consortium. (2004). The Gene Ontology (GO) database and informatics resource. Nucleic Acids Research, 32(Suppl. 1), D258–D261.

    Article  CAS  Google Scholar 

  88. Gittler, J. K., Shemer, A., Suárez-Fariñas, M., Fuentes-Duculan, J., Gulewicz, K. J., Wang, C. Q., et al. (2012). Progressive activation of T H 2/T H 22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. Journal of Allergy and Clinical Immunology, 130(6), 1344–1354.

    Article  CAS  Google Scholar 

  89. Goswami, R., & Kaplan, M. H. (2011). A brief history of IL-9. The Journal of Immunology, 186(6), 3283–3288.

    Article  PubMed  CAS  Google Scholar 

  90. Gould, H. J., & Sutton, B. J. (2008). IgE in allergy and asthma today. Nature Reviews Immunology, 8(3), 205–217.

    Article  PubMed  CAS  Google Scholar 

  91. Grazia Roncarolo, M., Gregori, S., Battaglia, M., Bacchetta, R., Fleischhauer, K., & Levings, M. K. (2006). Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunological Reviews, 212(1), 28–50.

    Article  Google Scholar 

  92. Grosso, G., Bella, F., Godos, J., Sciacca, S., Del Rio, D., Ray, S., et al. (2017). Possible role of diet in cancer: Systematic review and multiple meta-analyses of dietary patterns, lifestyle factors, and cancer risk. Nutrition Reviews, 75(6), 405–419.

    Article  PubMed  Google Scholar 

  93. Hachem, J. P., Crumrine, D., Fluhr, J., Brown, B. E., Feingold, K. R., & Elias, P. M. (2003). pH directly regulates epidermal permeability barrier homeostasis, and stratum corneum integrity/cohesion. Journal of Investigative Dermatology, 121(2), 345–353.

    Article  CAS  Google Scholar 

  94. Hachem, J. P., Houben, E., Crumrine, D., Man, M. Q., Schurer, N., Roelandt, T., et al. (2006). Serine protease signaling of epidermal permeability barrier homeostasis. Journal of Investigative Dermatology, 126(9), 2074–2086.

    Article  CAS  Google Scholar 

  95. Hahn, W. C., & Weinberg, R. A. (2002). Rules for making human tumor cells. New England Journal of Medicine, 347(20), 1593–1603.

    Article  CAS  Google Scholar 

  96. Ham, H. J., Andeweg, A. C., & Boer, R. J. (2013). Induction of appropriate Th-cell phenotypes: Cellular decision-making in heterogeneous environments. Parasite Immunology, 35(11), 318–330.

    PubMed  Google Scholar 

  97. Hammad, H., & Lambrecht, B. N. (2008). Dendritic cells and epithelial cells: Linking innate and adaptive immunity in asthma. Nature Reviews Immunology, 8(3), 193–204.

    Article  PubMed  CAS  Google Scholar 

  98. Han, J. M., Patterson, S. J., Speck, M., Ehses, J. A., & Levings, M. K. (2014). Insulin inhibits IL-10-mediated regulatory T cell function: Implications for obesity. The Journal of Immunology, 192(2), 623–629.

    Article  PubMed  CAS  Google Scholar 

  99. Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: The next generation. Cell, 144(5), 646–674.

    Article  CAS  PubMed  Google Scholar 

  100. Hansemann, D. (1890). Ueber asymmetrische Zelltheilung in Epithelkrebsen und deren biologische Bedeutung. Virchows Archiv, 119(2), 299–326.

    Article  Google Scholar 

  101. Hirata, Y., Bruchovsky, N., & Aihara, K. (2010). Development of a mathematical model that predicts the outcome of hormone therapy for prostate cancer. Journal of Theoretical Biology, 264(2), 517–527.

    Article  PubMed  CAS  Google Scholar 

  102. Hirata, Y., Morino, K., Akakura, K., Higano, C. S., Bruchovsky, N., Gambol, T., et al. (2015). Intermittent androgen suppression: Estimating parameters for individual patients based on initial PSA data in response to androgen deprivation therapy. PloS One, 10(6), e0130372.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Höfer, T., Nathansen, H., Löhning, M., Radbruch, A., & Heinrich, R. (2002). GATA-3 transcriptional imprinting in Th2 lymphocytes: A mathematical model. Proceedings of the National Academy of Sciences, 99(14), 9364–9368.

    Article  CAS  Google Scholar 

  104. Hoffman, D. R., Kroll, L. M., Basehoar, A., Reece, B., Cunningham, C. T., & Koenig, D. W. (2014). Immediate and extended effects of sodium lauryl sulphate exposure on stratum corneum natural moisturizing factor. International Journal of Cosmetic Science, 36(1), 93–101.

    Article  PubMed  CAS  Google Scholar 

  105. Hoffman, D. R., Kroll, L. M., Basehoar, A., Reece, B., Cunningham, C. T., & Koenig, D. W. (2015). Immediate and extended effects of abrasion on stratum corneum natural moisturizing factor. Skin Research and Technology, 21(3), 366–372.

    Article  PubMed  CAS  Google Scholar 

  106. Hollstein, M., Sidransky, D., Vogelstein, B., & Harris, C. C. (1991). p53 mutations in human cancers. Science, 253(5015), 49–53.

    Article  PubMed  CAS  Google Scholar 

  107. Horimukai, K., Morita, K., Narita, M., Kondo, M., Kitazawa, H., Nozaki, M., et al. (2014). Application of moisturizer to neonates prevents development of atopic dermatitis. Journal of Allergy and Clinical Immunology, 134(4), 824–830.

    Article  Google Scholar 

  108. Horn, H., Lawrence, M. S., Chouinard, C. R., Shrestha, Y., Hu, J. X., Worstell, E., et al. (2017). Expanding discovery from cancer genomes by integrating protein network analyses with in vivo tumorigenesis assays. bioRxiv, 151977.

    Google Scholar 

  109. Hovnanian, A. (2013). Netherton syndrome: Skin inflammation and allergy by loss of protease inhibition. Cell and Tissue Research, 351(2), 289–300.

    Article  PubMed  CAS  Google Scholar 

  110. Howell, M. D., Kim, B. E., Gao, P., Grant, A. V., Boguniewicz, M., DeBenedetto, A., et al. (2007). Cytokine modulation of atopic dermatitis filaggrin skin expression. Journal of Allergy and Clinical Immunology, 120(1), 150–155.

    Article  CAS  Google Scholar 

  111. Howes, A., Stimpson, P., Redford, P., Gabrysova, L., & O’Garra, A. (2014). Interleukin-10: Cytokines in anti-inflammation and tolerance. In Cytokine frontiers (pp. 327–352). Tokyo: Springer.

    Chapter  Google Scholar 

  112. Huang, S. (2011). Systems biology of stem cells: Three useful perspectives to help overcome the paradigm of linear pathways. Philosophical Transactions of the Royal Society of London B: Biological Sciences, 366(1575), 2247–2259.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. Huang, S. (2011). On the intrinsic inevitability of cancer: From foetal to fatal attraction. Seminars in Cancer Biology, 21(3), 183–199.

    Article  PubMed  Google Scholar 

  114. Huang, S. (2013). Genetic and non-genetic instability in tumor progression: Link between the fitness landscape and the epigenetic landscape of cancer cells. Cancer and Metastasis Reviews, 32(3–4), 423–448.

    Article  PubMed  CAS  Google Scholar 

  115. Huang, S., Eichler, G., Bar-Yam, Y., & Ingber, D. E. (2005). Cell fates as high-dimensional attractor states of a complex gene regulatory network. Physical Review Letters, 94(12), 128701.

    Article  PubMed  CAS  Google Scholar 

  116. Huang, S., & Ingber, D. E. (2007). A non-genetic basis for cancer progression and metastasis: Self-organizing attractors in cell regulatory networks. Breast Disease, 26(1), 27–54.

    Article  Google Scholar 

  117. Huang, S., & Kauffman, S. A. (2009). Complex GRN regulatory networks: From structure to biological observables: Cell fate determination. In Encyclopedia of complexity and systems science (pp. 1180–1213). New York: Springer.

    Chapter  Google Scholar 

  118. Hudson, T. J., Anderson, W., Aretz, A., Barker, A. D., Bell, C., Bernabé, R. R., et al. (2010). International network of cancer genome projects. Nature, 464(7291), 993–998.

    Article  PubMed  CAS  Google Scholar 

  119. Irvine, A. D., McLean, W. I., & Leung, D. Y. (2011). Filaggrin mutations associated with skin and allergic diseases. New England Journal of Medicine, 365(14), 1315–1327.

    Article  CAS  Google Scholar 

  120. Ivanova, E. A., & Orekhov, A. N. (2015). T helper lymphocyte subsets and plasticity in autoimmunity and cancer: An overview. BioMed Research International, 2015, 9. Article ID 327470.

    Google Scholar 

  121. Kanehisa, M., Furumichi, M., Tanabe, M., Sato, Y., & Morishima, K. (2017). KEGG: New perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Research, 45(D1), D353–D361.

    Article  PubMed  CAS  Google Scholar 

  122. Kaneko, K. (2011). Characterization of stem cells and cancer cells on the basis of gene expression profile stability, plasticity, and robustness. Bioessays, 33(6), 403–413.

    Article  PubMed  CAS  Google Scholar 

  123. Kanno, Y., Vahedi, G., Hirahara, K., Singleton, K., & O’Shea, J. J. (2012). Transcriptional and epigenetic control of T helper cell specification: Molecular mechanisms underlying commitment and plasticity. Annual Review of Immunology, 30, 707–731.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Kaplan, D. H., Igyártó, B. Z., & Gaspari, A. A. (2012). Early immune events in the induction of allergic contact dermatitis. Nature Reviews Immunology, 12(2), 114–124.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  125. Kaplan, M. H. (2013). Th9 cells: Differentiation and disease. Immunological Reviews, 252(1), 104–115.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  126. Kauffman, S. (1971). Gene regulation networks: A theory for their global structure and behaviors. Current Topics in Developmental Biology, 6, 145–182.

    Article  PubMed  CAS  Google Scholar 

  127. Kauffman, S. A. (1969). Metabolic stability and epigenesis in randomly constructed genetic nets. Journal of Theoretical Biology, 22(3), 437–467.

    Article  PubMed  CAS  Google Scholar 

  128. Kawasaki, H., Nagao, K., Kubo, A., Hata, T., Shimizu, A., Mizuno, H., et al. (2012). Altered stratum corneum barrier and enhanced percutaneous immune responses in filaggrin-null mice. Journal of Allergy and Clinical Immunology, 129(6), 1538–1546.

    Article  CAS  Google Scholar 

  129. Kezic, S., O’regan, G. M., Yau, N., Sandilands, A., Chen, H., Campbell, L. E., et al. (2011). Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity. Allergy, 66(7), 934–940.

    Article  PubMed  CAS  Google Scholar 

  130. Kleinewietfeld, M., & Hafler, D. A. (2013). The plasticity of human Treg and Th17 cells and its role in autoimmunity. Seminars in Immunology, 25(4), 305–312.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  131. Knosp, C. A., & Johnston, J. A. (2012). Regulation of CD4+ T-cell polarization by suppressor of cytokine signalling proteins. Immunology, 135(2), 101–111.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Komatsu, N., Saijoh, K., Kuk, C., Liu, A. C., Khan, S., Shirasaki, F., et al. (2007). Human tissue kallikrein expression in the stratum corneum and serum of atopic dermatitis patients. Experimental Dermatology, 16(6), 513–519.

    Article  PubMed  CAS  Google Scholar 

  133. Kong, H. H., Oh, J., Deming, C., Conlan, S., Grice, E. A., Beatson, M. A., et al. (2012). Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Research, 22(5), 850–859.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  134. Krogan, N. J., Lippman, S., Agard, D. A., Ashworth, A., & Ideker, T. (2015). The cancer cell map initiative: Defining the hallmark networks of cancer. Molecular Cell, 58(4), 690–698.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  135. Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., et al. (2015). Integrative analysis of 111 reference human epigenomes. Nature, 518(7539), 317–330.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  136. Kundu, J. K., & Surh, Y. J. (2008). Inflammation: Gearing the journey to cancer. Mutation Research/Reviews in Mutation Research, 659(1), 15–30.

    Article  CAS  Google Scholar 

  137. Kuo, I. H., Yoshida, T., De Benedetto, A., & Beck, L. A. (2013). The cutaneous innate immune response in patients with atopic dermatitis. Journal of Allergy and Clinical Immunology, 131(2), 266–278.

    Article  CAS  Google Scholar 

  138. Lambrecht, B. N., & Hammad, H. (2010). The role of dendritic and epithelial cells as master regulators of allergic airway inflammation. The Lancet, 376(9743), 835–843.

    Article  CAS  Google Scholar 

  139. Land, H., Parada, L. F., & Weinberg, R. A. (1983). Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature, 304(5927), 596–602.

    Article  PubMed  CAS  Google Scholar 

  140. Lasry, A., & Ben-Neriah, Y. (2015). Senescence-associated inflammatory responses: Aging and cancer perspectives. Trends in Immunology, 36(4), 217–228.

    Article  PubMed  CAS  Google Scholar 

  141. Lathia, J. D., Mack, S. C., Mulkearns-Hubert, E. E., Valentim, C. L., & Rich, J. N. (2015). Cancer stem cells in glioblastoma. Genes & Development, 29(12), 1203–1217.

    Article  CAS  Google Scholar 

  142. Lee, S. E., Kim, J. M., Jeong, S. K., Jeon, J. E., Yoon, H. J., Jeong, M. K., et al. (2010). Protease-activated receptor-2 mediates the expression of inflammatory cytokines, antimicrobial peptides, and matrix metalloproteinases in keratinocytes in response to Propionibacterium acnes. Archives of Dermatological Research, 302(10), 745–756.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  143. Lee, Y. K., Mukasa, R., Hatton, R. D., & Weaver, C. T. (2009). Developmental plasticity of Th17 and Treg cells. Current Opinion in Immunology, 21(3), 274–280.

    Article  PubMed  CAS  Google Scholar 

  144. Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1998). Genetic instabilities in human cancers. Nature, 396(6712), 643–649.

    Article  PubMed  CAS  Google Scholar 

  145. Leung, D. Y. (2000). Atopic dermatitis: New insights and opportunities for therapeutic intervention. Journal of Allergy and Clinical Immunology, 105(5), 860–876.

    Article  CAS  Google Scholar 

  146. Li, C., & Wang, J. (2013). Quantifying cell fate decisions for differentiation and reprogramming of a human stem cell network: Landscape and biological paths. PLoS Computational Biology, 9(8), e1003165.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  147. Li, C., & Wang, J. (2014). Quantifying the underlying landscape and paths of cancer. Journal of the Royal Society Interface, 11(100), 20140774.

    Article  PubMed Central  CAS  Google Scholar 

  148. Li, C. W., Xia, W., Huo, L., Lim, S. O., Wu, Y., Hsu, J. L., et al. (2012). Epithelial–mesenchymal transition induced by TNF-α requires NF-κB-mediated transcriptional upregulation of Twist1. Cancer Research, 72(5), 1290–1300.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  149. Liston, A., & Gray, D. H. (2014). Homeostatic control of regulatory T cell diversity. Nature Reviews Immunology, 14(3), 154–165.

    Article  PubMed  CAS  Google Scholar 

  150. Liu, Z., Li, Z., Mao, K., Zou, J., Wang, Y., Tao, Z., et al. (2009). Dec2 promotes Th2 cell differentiation by enhancing IL-2R signaling. The Journal of Immunology, 183(10), 6320–6329.

    Article  PubMed  CAS  Google Scholar 

  151. Loeb, L. A., & Harris, C. C. (2008). Advances in chemical carcinogenesis: A historical review and prospective. Cancer Research, 68(17), 6863–6872.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  152. Longo, V. D., & Fontana, L. (2010). Calorie restriction and cancer prevention: Metabolic and molecular mechanisms. Trends in Pharmacological Sciences, 31(2), 89–98.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  153. Longo, V. D., & Mattson, M. P. (2014). Fasting: Molecular mechanisms and clinical applications. Cell Metabolism, 19(2), 181–192.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  154. Lu, Y., Hong, S., Li, H., Park, J., Hong, B., Wang, L., et al. (2012). Th9 cells promote antitumor immune responses in vivo. The Journal of Clinical Investigation, 122(11), 4160.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  155. MacIver, N. J., Michalek, R. D., & Rathmell, J. C. (2013). Metabolic regulation of T lymphocytes. Annual Review of Immunology, 31, 259–283.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  156. Magi, S., Iwamoto, K., & Okada-Hatakeyama, M. (2017). Current status of mathematical modeling of cancer – From the viewpoint of cancer hallmarks. Current Opinion in Systems Biology, 2, 39–48.

    Article  Google Scholar 

  157. Mahalingam, D., Kong, C. M., Lai, J., Tay, L. L., Yang, H., & Wang, X. (2012). Reversal of aberrant cancer methylome and transcriptome upon direct reprogramming of lung cancer cells. Scientific Reports, 2, 592.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  158. Man, M. Q., Hatano, Y., Lee, S. H., Man, M., Chang, S., Feingold, K. R., et al. (2008). Characterization of a hapten-induced, murine model with multiple features of atopic dermatitis: Structural, immunologic, and biochemical changes following single versus multiple oxazolone challenges. Journal of Investigative Dermatology, 128(1), 79–86.

    Article  CAS  Google Scholar 

  159. Mancini, A. J., Kaulback, K., & Chamlin, S. L. (2008). The socioeconomic impact of atopic dermatitis in the United States: A systematic review. Pediatric Dermatology, 25(1), 1–6.

    Article  PubMed  Google Scholar 

  160. Mani, S. A., Guo, W., Liao, M. J., Eaton, E. N., Ayyanan, A., Zhou, A. Y., et al. (2008). The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell, 133(4), 704–715.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  161. Martinez-Sanchez, M. E., Mendoza, L., Villarreal, C., & Álvarez-Buylla, E. R. (2015). A minimal regulatory network of extrinsic and intrinsic factors recovers observed patterns of CD4+ T cell differentiation and plasticity. PLoS Computational Biology, 11(6), e1004324.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  162. McAleer, M. A., & Irvine, A. D. (2013). The multifunctional role of filaggrin in allergic skin disease. Journal of Allergy and Clinical Immunology, 131(2), 280–291.

    Article  CAS  Google Scholar 

  163. McGirt, L. Y., & Beck, L. A. (2006). Innate immune defects in atopic dermatitis. Journal of Allergy and Clinical Immunology, 118(1), 202–208.

    Article  CAS  Google Scholar 

  164. McLaughlin, T., Liu, L. F., Lamendola, C., Shen, L., Morton, J., Rivas, H., et al. (2014). T-cell profile in adipose tissue is associated with insulin resistance and systemic inflammation in humans. Arteriosclerosis, Thrombosis, and Vascular Biology, 34(12), 2637–2643.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  165. Méndez-López, L. F., Davila-Velderrain, J., Domínguez-Hüttinger, E., Enríquez-Olguín, C., Martínez-García, J. C., & Álvarez-Buylla, E. R. (2017). Gene regulatory network underlying the immortalization of epithelial cells. BMC Systems Biology, 11(1), 24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  167. Mendoza, L., & Álvarez-Buylla, E. R. (1998). Dynamics of the genetic regulatory network for arabidopsis thaliana flower morphogenesis. Journal of Theoretical Biology, 193(2), 307–319.

    Article  PubMed  CAS  Google Scholar 

  168. Mendoza, L., Thieffry, D., & Álvarez-Buylla, E. R. (1999). Genetic control of flower morphogenesis in Arabidopsis thaliana: A logical analysis. Bioinformatics, 15, 593–606.

    Article  PubMed  CAS  Google Scholar 

  169. Micalizzi, D. S., Farabaugh, S. M., & Ford, H. L. (2010). Epithelial-mesenchymal transition in cancer: Parallels between normal development and tumor progression. Journal of Mammary Gland Biology and Neoplasia, 15(2), 117–134.

    Article  PubMed  PubMed Central  Google Scholar 

  170. Milanovic, M., Fan, D. N., Belenki, D., Däbritz, J. H. M., Zhao, Z., Yu, Y., et al. (2018). Senescence-associated reprogramming promotes cancer stemness. Nature, 553, 96–100.

    Article  PubMed  CAS  Google Scholar 

  171. Milo, R., Shen-Orr, S., Itzkovitz, S., Kashtan, N., Chklovskii, D., & Alon, U. (2002). Network motifs: Simple building blocks of complex networks. Science, 298(5594), 824–827.

    Article  PubMed  CAS  Google Scholar 

  172. Morel, A. P., Lièvre, M., Thomas, C., Hinkal, G., Ansieau, S., & Puisieux, A. (2008). Generation of breast cancer stem cells through epithelial-mesenchymal transition. PloS One, 3(8), e2888.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  173. Mosmann, T. R., Cherwinski, H., Bond, M. W., Giedlin, M. A., & Coffman, R. L. (1986). Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. The Journal of Immunology, 136(7), 2348–2357.

    PubMed  CAS  Google Scholar 

  174. Muñoz-Espín, D., Cañamero, M., Maraver, A., Gómez-López, G., Contreras, J., Murillo-Cuesta, S., et al. (2013). Programmed cell senescence during mammalian embryonic development. Cell, 155(5), 1104–1118.

    Article  PubMed  CAS  Google Scholar 

  175. Murphy, K. M., & Stockinger, B. (2010). Effector T cell plasticity: Flexibility in the face of changing circumstances. Nature Immunology, 11(8), 674–680.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  176. Myers, J. M. B., Martin, L. J., Kovacic, M. B., Mersha, T. B., He, H., Pilipenko, V., et al. (2014). Epistasis between serine protease inhibitor Kazal-type 5 (SPINK5) and thymic stromal lymphopoietin (TSLP) genes contributes to childhood asthma. Journal of Allergy and Clinical Immunology, 134(4), 891–899.

    Article  CAS  Google Scholar 

  177. Nakamura, Y., Oscherwitz, J., Cease, K. B., Chan, S. M., Muñoz-Planillo, R., Hasegawa, M., et al. (2013). Staphylococcus δ-toxin induces allergic skin disease by activating mast cells. Nature, 503(7476), 397–401.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  178. Nakayamada, S., Takahashi, H., Kanno, Y., & O’Shea, J. J. (2012). Helper T cell diversity and plasticity. Current Opinion in Immunology, 24(3), 297–302.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  179. Naldi, A., Berenguier, D., Fauré, A., Lopez, F., Thieffry, D., & Chaouiya, C. (2009). Logical modelling of regulatory networks with GINsim 2.3. Biosystems, 97(2), 134–139.

    Article  PubMed  CAS  Google Scholar 

  180. Naldi, A., Carneiro, J., Chaouiya, C., & Thieffry, D. (2010). Diversity and plasticity of Th cell types predicted from regulatory network modelling. PLoS Computational Biology, 6(9), e1000912.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  181. Naldi, A., Monteiro, P. T., Müssel, C., Consortium for Logical Models and Tools, Kestler, H. A., Thieffry, D., et al. (2015). Cooperative development of logical modelling standards and tools with CoLoMoTo. Bioinformatics, 31(7), 1154–1159.

    Article  CAS  Google Scholar 

  182. Nestle, F. O., Di Meglio, P., Qin, J. Z., & Nickoloff, B. J. (2009). Skin immune sentinels in health and disease. Nature Reviews Immunology, 9(10), 679–691.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  183. Newell, L., Polak, M. E., Perera, J., Owen, C., Boyd, P., Pickard, C., et al. (2013). Sensitization via healthy skin programs Th2 responses in individuals with atopic dermatitis. Journal of Investigative Dermatology, 133(10), 2372–2380.

    Article  CAS  Google Scholar 

  184. Nnoruka, E. N., & Dermatology London Clinic. (2004). Tropical medicine rounds current epidemiology of atopic dermatitis in south-eastern Nigeria International Journal of Dermatology, 43(10), 739–744. Wiley online library, ISSN:1365-4632.

    Google Scholar 

  185. Nograles, K. E., Zaba, L. C., Guttman-Yassky, E., Fuentes-Duculan, J., Suárez-Fariñas, M., Cardinale, I., et al. (2008). Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. British Journal of Dermatology, 159(5), 1092–1102.

    CAS  Google Scholar 

  186. Norris, D. A. (2005). Mechanisms of action of topical therapies and the rationale for combination therapy. Journal of the American Academy of Dermatology, 53(1), S17–S25.

    Article  PubMed  Google Scholar 

  187. Nuorti, J. P., Butler, J. C., Crutcher, J. M., Guevara, R., Welch, D., Holder, P., et al. (1998). An outbreak of multidrug-resistant pneumococcal pneumonia and bacteremia among unvaccinated nursing home residents. New England Journal of Medicine, 338(26), 1861–1868.

    Article  CAS  Google Scholar 

  188. Olefsky, J. M., & Glass, C. K. (2010). Macrophages, inflammation, and insulin resistance. Annual Review of Physiology, 72, 219–246.

    Article  PubMed  CAS  Google Scholar 

  189. O’regan, G. M., Sandilands, A., McLean, W. I., & Irvine, A. D. (2009). Filaggrin in atopic dermatitis. Journal of Allergy and Clinical Immunology, 124(3), R2–R6.

    Article  CAS  Google Scholar 

  190. O’Shea, J. J., Gadina, M., & Kanno, Y. (2011). Cytokine signaling: Birth of a pathway. The Journal of Immunology, 187(11), 5475–5478.

    Article  PubMed  CAS  Google Scholar 

  191. O’Shea, J. J., & Paul, W. E. (2010). Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science, 327(5969), 1098–1102.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  192. Palmer, C. N., Irvine, A. D., Terron-Kwiatkowski, A., Zhao, Y., Liao, H., Lee, S. P., et al. (2006). Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nature Genetics, 38(4), 441–446.

    Article  PubMed  CAS  Google Scholar 

  193. Paternoster, L., Standl, M., Waage, J., Baurecht, H., Hotze, M., Strachan, D. P., et al. (2015). Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nature Genetics, 47(12), 1449–1456.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  194. Pearson, K. J., Baur, J. A., Lewis, K. N., Peshkin, L., Price, N. L., Labinskyy, N., et al. (2008). Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metabolism, 8(2), 157–168.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  195. Pérez-Ruiz, R. V., García-Ponce, B., Marsch-Martínez, N., Ugartechea-Chirino, Y., Villajuana-Bonequi, M., de Folter, S., et al. (2015). XAANTAL2 (AGL14) is an important component of the complex gene regulatory network that underlies Arabidopsis shoot apical meristem transitions. Molecular Plant, 8(5), 796–813.

    Article  PubMed  CAS  Google Scholar 

  196. Polak, P., Karlić, R., Koren, A., Thurman, R., Sandstrom, R., Lawrence, M. S., et al. (2015). Cell-of-origin chromatin organization shapes the mutational landscape of cancer. Nature, 518(7539), 360–364.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  197. Prina, E., Ranzani, O. T., & Torres, A. (2015). Community-acquired pneumonia. The Lancet, 386(9998), 1097–1108.

    Article  Google Scholar 

  198. Quail, D. F., Olson, O. C., Bhardwaj, P., Walsh, L. A., Akkari, L., Quick, M. L., et al. (2017). Obesity alters the lung myeloid cell landscape to enhance breast cancer metastasis through IL5 and GM-CSF. Nature Cell Biology, 19(8), ncb3578.

    Google Scholar 

  199. Radisky, D. C., & LaBarge, M. A. (2008). Epithelial-mesenchymal transition and the stem cell phenotype. Cell Stem Cell, 2(6), 511–512.

    Article  PubMed  CAS  Google Scholar 

  200. Ring, J., Alomar, A., Bieber, T., Deleuran, M., Fink-Wagner, A., Gelmetti, C., et al. (2012). Guidelines for treatment of atopic eczema (atopic dermatitis) Part I. Journal of the European Academy of Dermatology and Venereology, 26(8), 1045–1060.

    Article  PubMed  CAS  Google Scholar 

  201. Rivera, C. M., & Ren, B. (2013). Mapping human epigenomes. Cell, 155(1), 39–55.

    Article  PubMed  CAS  Google Scholar 

  202. Roedl, D., Traidl-Hoffmann, C., Ring, J., Behrendt, H., & Braun-Falco, M. (2009). Serine protease inhibitor lymphoepithelial Kazal type-related inhibitor tends to be decreased in atopic dermatitis. Journal of the European Academy of Dermatology and Venereology, 23(11), 1263.

    Article  PubMed  CAS  Google Scholar 

  203. Roekevisch, E., Spuls, P. I., Kuester, D., Limpens, J., & Schmitt, J. (2014). Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: A systematic review. Journal of Allergy and Clinical Immunology, 133(2), 429–438.

    Article  CAS  Google Scholar 

  204. Rubin, H. (1985). Cancer as a dynamic developmental disorder. Cancer Research, 45(7), 2935–2942.

    PubMed  CAS  Google Scholar 

  205. Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M., & Toda, M. (1995). Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. The Journal of Immunology, 155(3), 1151–1164.

    PubMed  CAS  Google Scholar 

  206. Sandilands, A., Sutherland, C., Irvine, A. D., & McLean, W. I. (2009). Filaggrin in the frontline: Role in skin barrier function and disease. Journal of Cell Science, 122(9), 1285–1294.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  207. Saraiva, M., & O’garra, A. (2010). The regulation of IL-10 production by immune cells. Nature Reviews Immunology, 10(3), 170–181.

    Article  PubMed  CAS  Google Scholar 

  208. Savignac, M., Edir, A., Simon, M., & Hovnanian, A. (2011). Darier disease: A disease model of impaired calcium homeostasis in the skin. Biochimica et Biophysica Acta—Molecular Cell Research, 1813(5), 1111–1117.

    Article  CAS  Google Scholar 

  209. Schaerli, P., Willimann, K., Lang, A. B., Lipp, M., Loetscher, P., & Moser, B. (2000). CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. Journal of Experimental Medicine, 192(11), 1553–1562.

    Article  CAS  Google Scholar 

  210. Scharschmidt, T. C., Man, M. Q., Hatano, Y., Crumrine, D., Gunathilake, R., Sundberg, J. P., et al. (2009). Filaggrin deficiency confers a paracellular barrier abnormality that reduces inflammatory thresholds to irritants and haptens. Journal of Allergy and Clinical Immunology, 124(3), 496–506.

    Article  CAS  Google Scholar 

  211. Schmitt, E., Klein, M., & Bopp, T. (2014). Th9 cells, new players in adaptive immunity. Trends in Immunology, 35(2), 61–68.

    Article  PubMed  CAS  Google Scholar 

  212. Schoepe, S., Schäcke, H., May, E., & Asadullah, K. (2006). Glucocorticoid therapy-induced skin atrophy. Experimental Dermatology, 15(6), 406–420.

    Article  PubMed  CAS  Google Scholar 

  213. Schrag, S. J., Peña, C., Fernández, J., Sánchez, J., Gómez, V., Pérez, E., et al. (2001). Effect of short-course, high-dose amoxicillin therapy on resistant pneumococcal carriage: A randomized trial. JAMA, 286(1), 49–56.

    Article  PubMed  CAS  Google Scholar 

  214. Sharlow, E. R., Paine, C. S., Babiarz, L., Eisinger, M., Shapiro, S., & Seiberg, M. (2000). The protease-activated receptor-2 upregulates keratinocyte phagocytosis. Journal of Cell Science, 113(17), 3093–3101.

    PubMed  CAS  Google Scholar 

  215. Shih, C., Padhy, L. C., Murray, M., & Weinberg, R. A. (1981). Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature, 290, 261–264.

    Article  PubMed  CAS  Google Scholar 

  216. Shih, C., & Weinberg, R. A. (1982). Isolation of a transforming sequence from a human bladder carcinoma cell line. Cell, 29(1), 161–169.

    Article  PubMed  CAS  Google Scholar 

  217. Sidbury, R., Davis, D. M., Cohen, D. E., Cordoro, K. M., Berger, T. G., Bergman, J. N., et al. (2014). Guidelines of care for the management of atopic dermatitis: Section 3. Management and treatment with phototherapy and systemic agents. Journal of the American Academy of Dermatology, 71(2), 327–349.

    Article  PubMed  PubMed Central  Google Scholar 

  218. Simpson, E. L., Chalmers, J. R., Hanifin, J. M., Thomas, K. S., Cork, M. J., McLean, W. I., et al. (2014). Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention. Journal of Allergy and Clinical Immunology, 134(4), 818–823.

    Article  Google Scholar 

  219. Sotiropoulou, G., & Pampalakis, G. (2010). Kallikrein-related peptidases: Bridges between immune functions and extracellular matrix degradation. Biological Chemistry, 391(4), 321–331.

    Article  PubMed  CAS  Google Scholar 

  220. Soto, A. M., & Sonnenschein, C. (2004). The somatic mutation theory of cancer: Growing problems with the paradigm?. Bioessays, 26(10), 1097–1107.

    Article  PubMed  CAS  Google Scholar 

  221. Storer, M., Mas, A., Robert-Moreno, A., Pecoraro, M., Ortells, M. C., Di Giacomo, V., et al. (2013). Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell, 155(5), 1119–1130.

    Article  PubMed  CAS  Google Scholar 

  222. Stratton, M. R., Campbell, P. J., & Futreal, P. A. (2009). The cancer genome. Nature, 458(7239), 719–724.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  223. Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., et al. (2005). Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proceedings of the National Academy of Sciences, 102(43), 15545–15550.

    Article  CAS  Google Scholar 

  224. Sugiura, A., Nomura, T., Mizuno, A., & Imokawa, G. (2014). Reevaluation of the non-lesional dry skin in atopic dermatitis by acute barrier disruption: An abnormal permeability barrier homeostasis with defective processing to generate ceramide. Archives of Dermatological Research, 306(5), 427–440.

    Article  PubMed  CAS  Google Scholar 

  225. Taïeb, A., Seneschal, J., & Mossalayi, M. D. (2012). Biologics in atopic dermatitis. JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 10(3), 174–178.

    PubMed  Google Scholar 

  226. Takai, T., & Ikeda, S. (2011). Barrier dysfunction caused by environmental proteases in the pathogenesis of allergic diseases. Allergology International, 60(1), 25–35.

    Article  PubMed  CAS  Google Scholar 

  227. Tanaka, G., Christodoulides, P., Domínguez-Hüttinger, E., Aihara, K., & Tanaka, R. J. (2018). Bifurcation analysis of a mathematical model of atopic dermatitis to determine patient-specific effects of treatments on dynamic phenotypes. Journal of Theoretical Biology, 448, 66–79.

    Article  PubMed  CAS  Google Scholar 

  228. Tanaka, R. J., Ono, M., & Harrington, H. A. (2011). Skin barrier homeostasis in atopic dermatitis: Feedback regulation of kallikrein activity. PloS One, 6(5), e19895.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  229. Tang, T. S., Bieber, T., & Williams, H. C. (2014). Are the concepts of induction of remission and treatment of subclinical inflammation in atopic dermatitis clinically useful?. Journal of Allergy and Clinical Immunology, 133(6), 1615–1625.

    Article  Google Scholar 

  230. Terui, T., Hirao, T., Sato, Y., Uesugi, T., Honda, M., Iguchi, M., et al. (1998). An increased ratio of interleukin-1 receptor antagonist to interleukin-1α in inflammatory skin diseases. Experimental Dermatology, 7(6), 327–334.

    Article  PubMed  CAS  Google Scholar 

  231. Thyssen, J. P., & Kezic, S. (2014). Causes of epidermal filaggrin reduction and their role in the pathogenesis of atopic dermatitis. Journal of Allergy and Clinical Immunology, 134(4), 792–799.

    Article  CAS  Google Scholar 

  232. Tu, C. L., Crumrine, D. A., Man, M. Q., Chang, W., Elalieh, H., You, M., et al. (2012). Ablation of the calcium-sensing receptor in keratinocytes impairs epidermal differentiation and barrier function. Journal of Investigative Dermatology, 132(10), 2350–2359.

    Article  CAS  Google Scholar 

  233. Van Kruijsdijk, R. C., van der Wall, E., & Visseren, F. L. (2009). Obesity and cancer: The role of dysfunctional adipose tissue. Cancer Epidemiology and Prevention Biomarkers, 18(10), 2569–2578.

    Article  CAS  Google Scholar 

  234. Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M., & Stockinger, B. (2006). TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity, 24(2), 179–189.

    Article  CAS  PubMed  Google Scholar 

  235. Villarreal, C., Padilla-Longoria, P., & Álvarez-Buylla, E. R. (2012). General theory of genotype to phenotype mapping: Derivation of epigenetic landscapes from N-node complex gene regulatory networks. Physical Review Letters, 109(11), 118102.

    Article  PubMed  CAS  Google Scholar 

  236. Vinuesa, C. G., Fagarasan, S., & Dong, C. (2013). New territory for T follicular helper cells. Immunity, 39(3), 417–420.

    Article  PubMed  CAS  Google Scholar 

  237. Virchow, R. (1858). Die Cellularpathologie in ihrer Begründung auf physiologische und pathologische Gewebelehre: zwanzig Vorlesungen, gehalten während der Monate Februar, März und April 1858 im pathologischen Institute zu Berlin. Hirschwald.

    Google Scholar 

  238. Vogelstein, B., Fearon, E. R., Hamilton, S. R., Kern, S. E., Preisinger, A. C., Leppert, M., et al. (1988). Genetic alterations during colorectal-tumor development. New England Journal of Medicine, 319(9), 525–532.

    Article  CAS  Google Scholar 

  239. Wadonda-Kabondo, N., Sterne, J. A. C., Golding, J., Kennedy, C. T. C., Archer, C. B., Dunnill, M. G. S., et al. (2003). A prospective study of the prevalence and incidence of atopic dermatitis in children aged 0–42 months. British Journal of Dermatology, 149(5), 1023–1028. Epidemiology and Health Services Research.

    Google Scholar 

  240. Wang, G., Yuan, R., Zhu, X., & Ao, P. (2018). Endogenous molecular-cellular network cancer theory: A systems biology approach. In M. Bizzarri (Ed.), Systems biology. Methods in molecular biology (Vol. 1702). New York: Humana Press.

    Google Scholar 

  241. Wang, G., Zhu, X., Gu, J., & Ao, P. (2014). Quantitative implementation of the endogenous molecular–cellular network hypothesis in hepatocellular carcinoma. Interface Focus, 4(3), 20130064.

    Article  PubMed  PubMed Central  Google Scholar 

  242. Warrell, M. J. (2011). Intradermal rabies vaccination: The evolution and future of pre-and post-exposure prophylaxis. In Intradermal immunization (pp. 139–157). Berlin: Springer.

    Chapter  Google Scholar 

  243. Watson, I. R., Takahashi, K., Futreal, P. A., & Chin, L. (2013). Emerging patterns of somatic mutations in cancer. Nature Reviews Genetics, 14(10), 703–718.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  244. Weinberg, R. A. (1991). Tumor suppressor genes. Science, 254(5035), 1138–1146.

    Article  PubMed  CAS  Google Scholar 

  245. Weiner, H. L., da Cunha, A. P., Quintana, F., & Wu, H. (2011). Oral tolerance. Immunological Reviews, 241(1), 241–259.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  246. Weinstein, J. N., Collisson, E. A., Mills, G. B., Shaw, K. R. M., Ozenberger, B. A., Ellrott, K., et al. (2013). The cancer genome atlas pan-cancer analysis project. Nature Genetics, 45(10), 1113–1120.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  247. Willhauck, M. J., Mirancea, N., Vosseler, S., Pavesio, A., Boukamp, P., Mueller, M. M., et al. (2007). Reversion of tumor phenotype in surface transplants of skin SCC cells by scaffold-induced stroma modulation. Carcinogenesis, 28(3), 595–610.

    Article  PubMed  CAS  Google Scholar 

  248. Wills-Karp, M., Santeliz, J., & Karp, C. L. (2001). The germless theory of allergic disease: Revisiting the hygiene hypothesis. Nature Reviews Immunology, 1(1), 69–75.

    Article  PubMed  CAS  Google Scholar 

  249. Wuensche, A. (1998, January). Genomic regulation modeled as a network with basins of attraction. In Pacific Symposium on Biocomputing (Vol. 3, pp. 89–102).

    Google Scholar 

  250. Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., et al. (2003). Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. Journal of Clinical Investigation, 112(12), 1821.

    Article  PubMed Central  CAS  Google Scholar 

  251. Xu, J., Lamouille, S., & Derynck, R. (2009). TGF-β-induced epithelial to mesenchymal transition. Cell Research, 19(2), 156–172.

    Article  PubMed  CAS  Google Scholar 

  252. Xu, L., Kitani, A., Fuss, I., & Strober, W. (2007). Cutting edge: Regulatory T cells induce CD4+ CD25- Foxp3-T cells or are self-induced to become Th17 cells in the absence of exogenous TGF-β. The Journal of Immunology, 178(11), 6725–6729.

    Article  PubMed  CAS  Google Scholar 

  253. Yaffe, M. B. (2013). The scientific drunk and the lamppost: Massive sequencing efforts in cancer discovery and treatment. Science Signaling, 6(269), pe13.

    Google Scholar 

  254. Yamane, H., Zhu, J., & Paul, W. E. (2005). Independent roles for IL-2 and GATA-3 in stimulating naive CD4+ T cells to generate a Th2-inducing cytokine environment. Journal of Experimental Medicine, 202(6), 793–804.

    Article  CAS  Google Scholar 

  255. Yates, A., Bergmann, C., Van Hemmen, J. L., Stark, J., & Callard, R. (2000). Cytokine-modulated regulation of helper T cell populations. Journal of Theoretical Biology, 206(4), 539–560.

    Article  PubMed  CAS  Google Scholar 

  256. Ye, X., & Weinberg, R. A. (2015). Epithelial–mesenchymal plasticity: A central regulator of cancer progression. Trends in Cell Biology, 25(11), 675–686.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  257. Yoshimura, A., Naka, T., & Kubo, M. (2007). SOCS proteins, cytokine signalling and immune regulation. Nature Reviews Immunology, 7(6), 454–465.

    Article  PubMed  CAS  Google Scholar 

  258. Yoshimura, A., Suzuki, M., Sakaguchi, R., Hanada, T., & Yasukawa, H. (2012). SOCS, inflammation, and autoimmunity. Frontiers in Immunology, 3, 20.

    Article  PubMed  PubMed Central  Google Scholar 

  259. Yuan, R., Zhu, X., Radich, J. P., & Ao, P. (2016). From molecular interaction to acute promyelocytic leukemia: Calculating leukemogenesis and remission from endogenous molecular-cellular network. Scientific Reports, 6, 24307.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  260. Zhang, Y. (2013). Cancer embryonic stem cell-like attractors alongside deficiency of regulatory restraints of cell-division and cell-cycle. Journal of Genetic Syndromes and Gene Therapy, 4(130), 2.

    Google Scholar 

  261. Zhang, Z., Clarke, T. B., & Weiser, J. N. (2009). Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice. The Journal of Clinical Investigation, 119(7), 1899.

    PubMed  PubMed Central  CAS  Google Scholar 

  262. Zheng, T., Yu, J., Oh, M. H., & Zhu, Z. (2011). The atopic march: Progression from atopic dermatitis to allergic rhinitis and asthma. Allergy, Asthma & Immunology Research, 3(2), 67–73.

    Article  Google Scholar 

  263. Zhou, J. X., & Huang, S. (2011). Understanding gene circuits at cell-fate branch points for rational cell reprogramming. Trends in Genetics, 27(2), 55–62.

    Article  PubMed  CAS  Google Scholar 

  264. Zhu, J., Yamane, H., & Paul, W. E. (2009). Differentiation of effector CD4 T cell populations. Annual Review of Immunology, 28, 445–489.

    Article  CAS  Google Scholar 

  265. Zhu, X., Yuan, R., Hood, L., & Ao, P. (2015). Endogenous molecular-cellular hierarchical modeling of prostate carcinogenesis uncovers robust structure. Progress in Biophysics and Molecular Biology, 117(1), 30–42.

    Article  PubMed  CAS  Google Scholar 

  266. Zitvogel, L., Pietrocola, F., & Kroemer, G. (2017). Nutrition, inflammation and cancer. Nature Immunology, 18(8), 843–850.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Ciudad Universitaria, UNAM, Instituto de Ecología, Ciudad de México, Distrito Federal, Mexico

    María Elena Álvarez-Buylla Roces & Mariana Esther Martínez-Sánchez

  2. Departamento de Control Automático, CINVESTAV, Ciudad de México, Distrito Federal, Mexico

    Juan Carlos Martínez-García

  3. CSIL, Massachusetts Institute of Technology, Cambridge, MA, USA

    José Dávila-Velderrain

  4. Centro de Ciencias Matemáticas, UNAM, Morelia, México

    Elisa Domínguez-Hüttinger

Authors
  1. María Elena Álvarez-Buylla Roces
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juan Carlos Martínez-García
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. José Dávila-Velderrain
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elisa Domínguez-Hüttinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mariana Esther Martínez-Sánchez
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Álvarez-Buylla Roces, M.E., Martínez-García, J.C., Dávila-Velderrain, J., Domínguez-Hüttinger, E., Martínez-Sánchez, M.E. (2018). Case Studies. In: Modeling Methods for Medical Systems Biology. Advances in Experimental Medicine and Biology, vol 1069. Springer, Cham. https://doi.org/10.1007/978-3-319-89354-9_3

Download citation

Publish with us

Policies and ethics

Search

Navigation