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Computational Stem Cell Biology pp 3–35Cite as

Agent-Based Modelling to Delineate Spatiotemporal Control Mechanisms of the Stem Cell Niche

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1975))

Abstract

Agent-based modelling (ABM) offers a framework to realistically couple subcellular signaling pathways to cellular behavior and macroscopic tissue organization. However, these models have been previously inaccessible to many systems biologists due to the difficulties with formulating and simulating multi-scale behavior. In this chapter, a review of the Compucell3D framework is presented along with a general workflow for transitioning from a well-mixed ODE model to an ABM. These techniques are demonstrated through a case study on the simulation of a Notch-Delta Positive Feedback, Lateral Inhibition (PFLI) gene circuit in the intestinal crypts. Specifically, techniques for gene circuit-driven hypothesis formation, geometry construction, selection of simulation parameters, and simulation quantification are presented.

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References

  1. Bianconi E, Piovesan A, Facchin F, Beraudi A, Casadei R, Frabetti F, Vitale L, Pelleri MC, Tassani S, Piva F, Perez-Amodio S, Strippoli P, Canaider S (2013) An estimation of the number of cells in the human body. Ann Hum Biol 40:463–471. https://doi.org/10.3109/03014460.2013.807878

    Article  Google Scholar 

  2. Hatano A, Chiba H, Moesa HA, Taniguchi T, Nagaie S, Yamanegi K, Takai-Igarashi T, Tanaka H, Fujibuchi W (2011) CELLPEDIA: a repository for human cell information for cell studies and differentiation analyses. Database 2011:bar046. https://doi.org/10.1093/database/bar046

    Article  CAS  Google Scholar 

  3. Clamp M, Fry B, Kamal M, Xie X, Cuff J, Lin MF, Kellis M, Lindblad-Toh K, Lander ES (2007) Distinguishing protein-coding and noncoding genes in the human genome. Proc Natl Acad Sci 104:19428–19433. https://doi.org/10.1073/pnas.0709013104

    Article  CAS  Google Scholar 

  4. Church DM, Goodstadt L, Hillier LW, Zody MC, Goldstein S, She X, Bult CJ, Agarwala R, Cherry JL, DiCuccio M, Hlavina W, Kapustin Y, Meric P, Maglott D, Birtle Z, Marques AC, Graves T, Zhou S, Teague B, Potamousis K, Churas C, Place M, Herschleb J, Runnheim R, Forrest D, Amos-Landgraf J, Schwartz DC, Cheng Z, Lindblad-Toh K, Eichler EE, Ponting CP, Consortium TMGS (2009) Lineage-specific biology revealed by a finished genome assembly of the mouse. PLoS Biol 7:e1000112. https://doi.org/10.1371/journal.pbio.1000112

    Article  CAS  Google Scholar 

  5. Tsompana M, Buck MJ (2014) Chromatin accessibility: a window into the genome. Epigenetics Chromatin 7:33. https://doi.org/10.1186/1756-8935-7-33

    Article  Google Scholar 

  6. Kumar A, Garg S, Garg N (2014) Regulation of gene expression. In: Reviews in cell biology and molecular medicine. American Cancer Society, Atlanta, pp 1–59

    Google Scholar 

  7. Hernando-Herraez I, Garcia-Perez R, Sharp AJ, Marques-Bonet T (2015) DNA methylation: insights into human evolution. PLoS Genet 11:e1005661. https://doi.org/10.1371/journal.pgen.1005661

    Article  CAS  Google Scholar 

  8. Lambert SA, Jolma A, Campitelli LF, Das PK, Yin Y, Albu M, Chen X, Taipale J, Hughes TR, Weirauch MT (2018) The human transcription factors. Cell 172:650–665. https://doi.org/10.1016/j.cell.2018.01.029

    Article  CAS  Google Scholar 

  9. Chen K-Y, Srinivasan T, Tung K-L, Belmonte JM, Wang L, Murthy PKL, Choi J, Rakhilin N, King S, Varanko AK, Witherspoon M, Nishimura N, Glazier JA, Lipkin SM, Bu P, Shen X (2017) A Notch positive feedback in the intestinal stem cell niche is essential for stem cell self-renewal. Mol Syst Biol 13:927. https://doi.org/10.15252/msb.20167324

    Article  CAS  Google Scholar 

  10. Borggrefe T, Lauth M, Zwijsen A, Huylebroeck D, Oswald F, Giaimo BD (2016) The Notch intracellular domain integrates signals from Wnt, Hedgehog, TGFβ/BMP and hypoxia pathways. Biochim Biophys Acta 1863:303–313. https://doi.org/10.1016/j.bbamcr.2015.11.020

    Article  CAS  Google Scholar 

  11. Kay SK, Harrington HA, Shepherd S, Brennan K, Dale T, Osborne JM, Gavaghan DJ, Byrne HM (2017) The role of the Hes1 crosstalk hub in Notch-Wnt interactions of the intestinal crypt. PLoS Comput Biol 13:e1005400. https://doi.org/10.1371/journal.pcbi.1005400

    Article  CAS  Google Scholar 

  12. Ladyman J, Lambert J, Wiesner K (2013) What is a complex system? Eur J Philos Sci 3:33–67. https://doi.org/10.1007/s13194-012-0056-8

    Article  Google Scholar 

  13. Ross J, Arkin AP (2009) Complex systems: from chemistry to systems biology. Proc Natl Acad Sci 106:6433–6434. https://doi.org/10.1073/pnas.0903406106

    Article  Google Scholar 

  14. Whitesides GM, Ismagilov RF (1999) Complexity in chemistry. Science 284:89–92. https://doi.org/10.1126/science.284.5411.89F

    Article  CAS  Google Scholar 

  15. Weng G, Bhalla US, Iyengar R (1999) Complexity in biological signaling systems. Science 284:92–96. https://doi.org/10.1126/science.284.5411.92

    Article  CAS  Google Scholar 

  16. Koch C, Laurent G (1999) Complexity and the nervous system. Science 284:96–98. https://doi.org/10.1126/science.284.5411.96

    Article  CAS  Google Scholar 

  17. Cooke J (1973) Properties of the primary organization field in the embryo of Xenopus laevis: IV. Pattern formation and regulation following early inhibition of mitosis. Development 30:49–62

    CAS  Google Scholar 

  18. Lander AD, Kimble J, Clevers H, Fuchs E, Montarras D, Buckingham M, Calof AL, Trumpp A, Oskarsson T (2012) What does the concept of the stem cell niche really mean today? BMC Biol 10:19. https://doi.org/10.1186/1741-7007-10-19

    Article  Google Scholar 

  19. Rojas-Ríos P, González-Reyes A (2014) Concise review: the plasticity of stem cell niches: a general property behind tissue homeostasis and repair. Stem Cells 32:852–859. https://doi.org/10.1002/stem.1621

    Article  Google Scholar 

  20. Ferraro F, Celso CL, Scadden D (2010) Adult stem cells and their niches. Adv Exp Med Biol 695:155–168. https://doi.org/10.1007/978-1-4419-7037-4_11

    Article  CAS  Google Scholar 

  21. Morrison SJ, Spradling AC (2008) Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell 132:598–611. https://doi.org/10.1016/j.cell.2008.01.038

    Article  CAS  Google Scholar 

  22. Schofield R (1978) The relationship between the spleen colony-forming cell and the haematopoietic stem cell. Blood Cells 4:7–25

    CAS  Google Scholar 

  23. Snippert HJ, van der Flier LG, Sato T, van Es JH, van den Born M, Kroon-Veenboer C, Barker N, Klein AM, van Rheenen J, Simons BD, Clevers H (2010) Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Cell 143:134–144. https://doi.org/10.1016/j.cell.2010.09.016

    Article  CAS  Google Scholar 

  24. Clevers H (2013) The intestinal crypt, a prototype stem cell compartment. Cell 154:274–284. https://doi.org/10.1016/j.cell.2013.07.004

    Article  CAS  Google Scholar 

  25. Barker N (2014) Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration. Nat Rev Mol Cell Biol 15:19–33. https://doi.org/10.1038/nrm3721

    Article  CAS  Google Scholar 

  26. Meran L, Baulies A, Li VSW (2017) Intestinal stem cell niche: the extracellular matrix and cellular components. Stem Cells Int 2017:7970385. https://www.hindawi.com/journals/sci/2017/7970385/. Accessed 8 Apr 2018

    Article  Google Scholar 

  27. Gjorevski N, Ordóñez-Morán P (2017) Intestinal stem cell niche insights gathered from both in vivo and novel in vitro models. Stem Cells Int 2017:8387297. https://www.hindawi.com/journals/sci/2017/8387297/. Accessed 8 Apr 2018

    Article  Google Scholar 

  28. Durand A, Donahue B, Peignon G, Letourneur F, Cagnard N, Slomianny C, Perret C, Shroyer NF, Romagnolo B (2012) Functional intestinal stem cells after Paneth cell ablation induced by the loss of transcription factor Math1 (Atoh1). Proc Natl Acad Sci 109:8965–8970. https://doi.org/10.1073/pnas.1201652109

    Article  Google Scholar 

  29. Farin HF, Jordens I, Mosa MH, Basak O, Korving J, Tauriello DVF, de Punder K, Angers S, Peters PJ, Maurice MM, Clevers H (2016) Visualization of a short-range Wnt gradient in the intestinal stem-cell niche. Nature 530:340–343. https://doi.org/10.1038/nature16937

    Article  CAS  Google Scholar 

  30. Collier JR, Monk NAM, Maini PK, Lewis JH (1996) Pattern formation by lateral inhibition with feedback: a mathematical model of delta-notch intercellular signalling. J Theor Biol 183:429–446. https://doi.org/10.1006/jtbi.1996.0233

    Article  CAS  Google Scholar 

  31. Du H, Nie Q, Holmes WR (2015) The Interplay between Wnt mediated expansion and negative regulation of growth promotes robust intestinal crypt structure and homeostasis. PLoS Comput Biol 11:e1004285. https://doi.org/10.1371/journal.pcbi.1004285

    Article  CAS  Google Scholar 

  32. Qi Z, Li Y, Zhao B, Xu C, Liu Y, Li H, Zhang B, Wang X, Yang X, Xie W, Li B, Han J-DJ, Chen Y-G (2017) BMP restricts stemness of intestinal Lgr5+ stem cells by directly suppressing their signature genes. Nat Commun 8:13824. https://doi.org/10.1038/ncomms13824

    Article  CAS  Google Scholar 

  33. Walton KD, Whidden M, Kolterud Å, Shoffner SK, Czerwinski MJ, Kushwaha J, Parmar N, Chandhrasekhar D, Freddo AM, Schnell S, Gumucio DL (2016) Vilification in the mouse: Bmp signals control intestinal villus patterning. Development 143:427–436. https://doi.org/10.1242/dev.130112

    Article  CAS  Google Scholar 

  34. Turing AM (1952) The chemical basis of morphogenesis. Phil Trans R Soc Lond B 237:37–72. https://doi.org/10.1098/rstb.1952.0012

    Article  Google Scholar 

  35. Loeffler M, Stein R, Wichmann H-E, Potten CS, Kaur P, Chwalinski S (1986) Intestinal cell proliferation. I. A comprehensive model of steady-state proliferation in the crypt. Cell Prolif 19:627–645. https://doi.org/10.1111/j.1365-2184.1986.tb00763.x

    Article  CAS  Google Scholar 

  36. Potten CS, Loeffler M (1987) A comprehensive model of the crypts of the small intestine of the mouse provides insight into the mechanisms of cell migration and the proliferation hierarchy. J Theor Biol 127:381–391. https://doi.org/10.1016/S0022-5193(87)80136-4

    Article  CAS  Google Scholar 

  37. Meinzer HP, Sandblad B, Baur HJ (2008) Generation-dependent control mechanisms in cell proliferation and differentiation—the power of two. Cell Prolif 25:125–140. https://doi.org/10.1111/j.1365-2184.1992.tb01486.x

    Article  Google Scholar 

  38. Finney KJ, Appleton DR, Ince P, Sunter JP, Watson AJ (1988) Proliferative status of colonic mucosa in organ culture: 3H-thymidine-labelling studies and computer modelling. Virchows Arch B 56:397–405. https://doi.org/10.1007/BF02890043

    Article  Google Scholar 

  39. Lee E, Salic A, Krüger R, Heinrich R, Kirschner MW (2003) The roles of APC and axin derived from experimental and theoretical analysis of the Wnt pathway. PLoS Biol 1:e10. https://doi.org/10.1371/journal.pbio.0000010

    Article  Google Scholar 

  40. Cho K-H, Baek S, Sung M-H (2006) Wnt pathway mutations selected by optimal β-catenin signaling for tumorigenesis. FEBS Lett 580:3665–3670. https://doi.org/10.1016/j.febslet.2006.05.053

    Article  CAS  Google Scholar 

  41. Schmitz Y, Wolkenhauer O, Rateitschak K (2011) Nucleo-cytoplasmic shuttling of APC can maximize β-catenin/TCF concentration. J Theor Biol 279:132–142. https://doi.org/10.1016/j.jtbi.2011.03.018

    Article  CAS  Google Scholar 

  42. van Leeuwen IMM, Byrne HM, Jensen OE, King JR (2007) Elucidating the interactions between the adhesive and transcriptional functions of β-catenin in normal and cancerous cells. J Theor Biol 247:77–102. https://doi.org/10.1016/j.jtbi.2007.01.019

    Article  CAS  Google Scholar 

  43. Van Leeuwen IMM, Mirams GR, Walter A, Fletcher A, Murray P, Osborne J, Varma S, Young SJ, Cooper J, Doyle B, Pitt-Francis J, Momtahan L, Pathmanathan P, Whiteley JP, Chapman SJ, Gavaghan DJ, Jensen OE, King JR, Maini PK, Waters SL, Byrne HM (2009) An integrative computational model for intestinal tissue renewal. Cell Prolif 42:617–636. https://doi.org/10.1111/j.1365-2184.2009.00627.x

    Article  Google Scholar 

  44. Meineke FA, Potten CS, Loeffler M (2001) Cell migration and organization in the intestinal crypt using a lattice-free model. Cell Prolif 34:253–266. https://doi.org/10.1046/j.0960-7722.2001.00216.x

    Article  CAS  Google Scholar 

  45. Mirams GR, Byrne HM, King JR (2010) A multiple timescale analysis of a mathematical model of the Wnt/β-catenin signalling pathway. J Math Biol 60:131–160. https://doi.org/10.1007/s00285-009-0262-y

    Article  Google Scholar 

  46. Osborne JM, Walter A, Kershaw SK, Mirams GR, Fletcher AG, Pathmanathan P, Gavaghan D, Jensen OE, Maini PK, Byrne HM (2010) A hybrid approach to multi-scale modelling of cancer. Philos Trans R Soc Lond Math Phys Eng Sci 368:5013–5028. https://doi.org/10.1098/rsta.2010.0173

    Article  CAS  Google Scholar 

  47. Murray PJ, Walter A, Fletcher AG, Edwards CM, Tindall MJ, Maini PK (2011) Comparing a discrete and continuum model of the intestinal crypt. Phys Biol 8:026011. https://doi.org/10.1088/1478-3975/8/2/026011

    Article  Google Scholar 

  48. Murray PJ, Kang J-W, Mirams GR, Shin S-Y, Byrne HM, Maini PK, Cho K-H (2010) Modelling spatially regulated beta-catenin dynamics and invasion in intestinal crypts. Biophys J 99:716–725. https://doi.org/10.1016/j.bpj.2010.05.016

    Article  CAS  Google Scholar 

  49. Zhang L, Lander AD, Nie Q (2012) A reaction–diffusion mechanism influences cell lineage progression as a basis for formation, regeneration, and stability of intestinal crypts. BMC Syst Biol 6:93. https://doi.org/10.1186/1752-0509-6-93

    Article  CAS  Google Scholar 

  50. Buske P, Galle J, Barker N, Aust G, Clevers H, Loeffler M (2011) A comprehensive model of the spatio-temporal stem cell and tissue organisation in the intestinal crypt. PLoS Comput Biol 7:e1001045. https://doi.org/10.1371/journal.pcbi.1001045

    Article  CAS  Google Scholar 

  51. Pin C, Watson AJM, Carding SR (2012) Modelling the spatio-temporal cell dynamics reveals novel insights on cell differentiation and proliferation in the small intestinal crypt. PLoS One 7:e37115. https://doi.org/10.1371/journal.pone.0037115

    Article  CAS  Google Scholar 

  52. Swat MH, Thomas GL, Belmonte JM, Shirinifard A, Hmeljak D, Glazier JA (2012) Multi-scale modeling of tissues using CompuCell3D. Methods Cell Biol 110:325–366. https://doi.org/10.1016/B978-0-12-388403-9.00013-8

    Article  Google Scholar 

  53. Glazier JA, Balter A, Popławski NJ (2007) Magnetization to morphogenesis: a brief history of the glazier-Graner-Hogeweg model. In: Single-cell-based models in biology and medicine. Birkhäuser Basel, pp 79–9

    Google Scholar 

  54. Marée AFM, Grieneisen VA, Hogeweg P (2007) The cellular potts model and biophysical properties of cells, tissues and morphogenesis. In: Single-cell-based models in biology and medicine. Birkhäuser, Basel, pp 107–136

    Chapter  Google Scholar 

  55. Savill NJ, Merks RMH (2007) The cellular potts model in biomedicine. In: Single-cell-based models in biology and medicine. Birkhäuser, Basel, pp 137–150

    Chapter  Google Scholar 

  56. Chen N, Glazier JA, Izaguirre JA, Alber MS (2007) A parallel implementation of the Cellular Potts Model for simulation of cell-based morphogenesis. Comput Phys Commun 176:670–681. https://doi.org/10.1016/j.cpc.2007.03.007

    Article  CAS  Google Scholar 

  57. Swat MH, Thomas GL, Shirinifard A, Clendenon SG, Glazier JA (2015) Emergent stratification in solid tumors selects for reduced cohesion of tumor cells: a multi-cell, virtual-tissue model of tumor evolution using CompuCell3D. PLoS One 10:e0127972. https://doi.org/10.1371/journal.pone.0127972

    Article  CAS  Google Scholar 

  58. Abdulla T, Luna-Zurita L, de la Pompa JL, Schleich J-M, Summers R (2013) Epithelial to mesenchymal transition—The roles of cell morphology, labile adhesion and junctional coupling. Comput Methods Prog Biomed 111:435–446. https://doi.org/10.1016/j.cmpb.2013.05.018

    Article  Google Scholar 

  59. Boas SEM, Merks RMH (2015) Tip cell overtaking occurs as a side effect of sprouting in computational models of angiogenesis. BMC Syst Biol 9:86. https://doi.org/10.1186/s12918-015-0230-7

    Article  CAS  Google Scholar 

  60. Sluka JP, Fu X, Swat M, Belmonte JM, Cosmanescu A, Clendenon SG, Wambaugh JF, Glazier JA (2016) A liver-centric multiscale modeling framework for xenobiotics. PLoS One 11:e0162428. https://doi.org/10.1371/journal.pone.0162428

    Article  CAS  Google Scholar 

  61. Hutson MS, Leung MCK, Baker NC, Spencer RM, Knudsen TB (2017) Computational model of secondary palate fusion and disruption. Chem Res Toxicol 30:965–979. https://doi.org/10.1021/acs.chemrestox.6b00350

    Article  CAS  Google Scholar 

  62. Balter A, Merks RMH, Popławski NJ, Swat M, Glazier JA (2007) The glazier-Graner-Hogeweg model: extensions, future directions, and opportunities for further study. In: Single-cell-based models in biology and medicine. Birkhäuser, Basel, pp 151–167

    Chapter  Google Scholar 

  63. Ising E (1925) Beitrag zur Theorie des Ferromagnetismus. Z Für Phys 31:253–258. https://doi.org/10.1007/BF02980577

    Article  CAS  Google Scholar 

  64. Potts RB (1951) The mathematical investigation of some cooperative phenomena. Thesis

    Google Scholar 

  65. Weaire D, Kermode JP (1983) Computer simulation of a two-dimensional soap froth. Philos Mag B 48:245–259. https://doi.org/10.1080/13642818308228287

    Article  CAS  Google Scholar 

  66. Wealire D, Kermode JP (1984) Computer simulation of a two-dimensional soap froth II. Analysis of results. Philos Mag B 50:379–395. https://doi.org/10.1080/13642818408238863

    Article  Google Scholar 

  67. Steinberg MS (1963) Reconstruction of tissues by dissociated CELLS. Science 141:401–408. https://doi.org/10.1126/science.141.3579.401

    Article  CAS  Google Scholar 

  68. Steinberg MS (1970) Does differential adhesion govern self-assembly processes in histogenesis? Equilibrium configurations and the emergence of a hierarchy among populations of embryonic cells. J Exp Zool 173:395–433. https://doi.org/10.1002/jez.1401730406

    Article  CAS  Google Scholar 

  69. Glazier JA, Graner F (1993) Simulation of the differential adhesion driven rearrangement of biological cells. Phys Rev E 47:2128–2154. https://doi.org/10.1103/PhysRevE.47.2128

    Article  CAS  Google Scholar 

  70. Graner F, Glazier JA (1992) Simulation of biological cell sorting using a two-dimensional extended Potts model. Phys Rev Lett 69:2013–2016. https://doi.org/10.1103/PhysRevLett.69.2013

    Article  CAS  Google Scholar 

  71. Marée AFM, Hogeweg P (2002) Modelling Dictyostelium discoideum morphogenesis: the culmination. Bull Math Biol 64:327–353. https://doi.org/10.1006/bulm.2001.0277

    Article  CAS  Google Scholar 

  72. Marée AFM, Hogeweg P (2001) How amoeboids self-organize into a fruiting body: Multicellular coordination in Dictyostelium discoideum. Proc Natl Acad Sci 98:3879–3883. https://doi.org/10.1073/pnas.061535198

    Article  Google Scholar 

  73. Savill NJ, Hogeweg P (1997) Modelling morphogenesis: from single cells to crawling slugs. J Theor Biol 184:229–235. https://doi.org/10.1006/jtbi.1996.0237

    Article  Google Scholar 

  74. Merks RMH, Glazier JA (2006) Dynamic mechanisms of blood vessel growth. Nonlinearity 19:C1–C10. https://doi.org/10.1088/0951-7715/19/1/000

    Article  Google Scholar 

  75. Mombach JCM, de Almeida RMC, Iglesias JR (1993) Mitosis and growth in biological tissues. Phys Rev E 48:598–602. https://doi.org/10.1103/PhysRevE.48.598

    Article  CAS  Google Scholar 

  76. Manuals - CompuCell3D. http://www.compucell3d.org/Manuals. Accessed 10 Apr 2018

  77. Izaguirre JA, Chaturvedi R, Huang C, Cickovski T, Coffland J, Thomas G, Forgacs G, Alber M, Hentschel G, Newman SA, Glazier JA (2004) CompuCell, a multi-model framework for simulation of morphogenesis. Bioinformatics 20:1129–1137. https://doi.org/10.1093/bioinformatics/bth050

    Article  CAS  Google Scholar 

  78. Chandler D (1987) Introduction to modern statistical mechanics. Oxford University Press, Oxford

    Google Scholar 

  79. Metropolis N, Rosenbluth AW, Rosenbluth MN, Teller AH, Teller E (1953) Equation of state calculations by fast computing machines. J Chem Phys 21:1087–1092. https://doi.org/10.1063/1.1699114

    Article  CAS  Google Scholar 

  80. Hastings WK (1970) Monte Carlo sampling methods using Markov chains and their applications. Biometrika 57:97–109. https://doi.org/10.1093/biomet/57.1.97

    Article  Google Scholar 

  81. Hoff PD (2009) A first course in Bayesian statistical methods [electronic resource]. Springer, London, New York

    Book  Google Scholar 

  82. Hucka M, Finney A, Sauro HM, Bolouri H, Doyle JC, Kitano H, Arkin AP, Bornstein BJ, Bray D, Cornish-Bowden A, Cuellar AA, Dronov S, Gilles ED, Ginkel M, Gor V, Goryanin II, Hedley WJ, Hodgman TC, Hofmeyr J-H, Hunter PJ, Juty NS, Kasberger JL, Kremling A, Kummer U, Le Novère N, Loew LM, Lucio D, Mendes P, Minch E, Mjolsness ED, Nakayama Y, Nelson MR, Nielsen PF, Sakurada T, Schaff JC, Shapiro BE, Shimizu TS, Spence HD, Stelling J, Takahashi K, Tomita M, Wagner J, Wang J, Forum SBML (2003) The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models. Bioinforma Oxf Engl 19:524–531

    Article  CAS  Google Scholar 

  83. Main Page - SBML.caltech.edu. http://sbml.org/Main_Page. Accessed 10 Apr 2018

  84. Choi K, Medley JK, Cannistra C, Konig M, Smith L, Stocking K, Sauro HM (2016) Tellurium: a python based modeling and reproducibility platform for systems biology. bioR xiv:054601. https://doi.org/10.1101/054601

    Article  Google Scholar 

  85. Ingalls BP (2013) Mathematical modeling in systems biology: an introduction. MIT Press, Cambridge

    Google Scholar 

  86. Logan JD (2013) Applied mathematics. John Wiley & Sons, Hoboken

    Google Scholar 

  87. Bianchi C, Cirillo P, Gallegati M, Vagliasindi PA (2007) Validating and calibrating agent-based models: a case study. Comput Econ 30:245–264. https://doi.org/10.1007/s10614-007-9097-z

    Article  Google Scholar 

  88. Pope AJ, Gimblett R (2015) Linking Bayesian and agent-based models to simulate complex social-ecological systems in semi-arid regions. Front Environ Sci 3. https://doi.org/10.3389/fenvs.2015.00055

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Authors and Affiliations

  1. Department of Biomedical Engineering, Duke University, Durham, NC, USA

    Robert Mines, Kai-Yuan Chen & Xiling Shen

  2. Center for Genomic and Computational Biology, Duke University, Durham, NC, USA

    Kai-Yuan Chen & Xiling Shen

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  1. Robert Mines
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  2. Kai-Yuan Chen
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  3. Xiling Shen
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Correspondence to Xiling Shen .

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  1. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA

    Patrick Cahan

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Mines, R., Chen, KY., Shen, X. (2019). Agent-Based Modelling to Delineate Spatiotemporal Control Mechanisms of the Stem Cell Niche. In: Cahan, P. (eds) Computational Stem Cell Biology. Methods in Molecular Biology, vol 1975. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9224-9_1

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  • DOI: https://doi.org/10.1007/978-1-4939-9224-9_1

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