Systems Biology in Immunology: a Computational Modeling Perspective

Overview

Journal Annu Rev Immunol

Specialty Allergy & Immunology

Date 2011 Jan 12

PMID 21219182

Citations 94

Authors

Ronald N Germain

Martin Meier-Schellersheim

Aleksandra Nita-Lazar

Iain D C Fraser

Affiliations

Soon will be listed here.

Abstract

Systems biology is an emerging discipline that combines high-content, multiplexed measurements with informatic and computational modeling methods to better understand biological function at various scales. Here we present a detailed review of the methods used to create computational models and to conduct simulations of immune function. We provide descriptions of the key data-gathering techniques employed to generate the quantitative and qualitative data required for such modeling and simulation and summarize the progress to date in applying these tools and techniques to questions of immunological interest, including infectious disease. We include comments on what insights modeling can provide that complement information obtained from the more familiar experimental discovery methods used by most investigators and the reasons why quantitative methods are needed to eventually produce a better understanding of immune system operation in health and disease.

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References

Zeng Y, Cullen B . Sequence requirements for micro RNA processing and function in human cells. RNA. 2003; 9(1):112-23. PMC: 1370375. DOI: 10.1261/rna.2780503. View

Germain R . The art of the probable: system control in the adaptive immune system. Science. 2001; 293(5528):240-5. DOI: 10.1126/science.1062946. View

Hattne J, Fange D, Elf J . Stochastic reaction-diffusion simulation with MesoRD. Bioinformatics. 2005; 21(12):2923-4. DOI: 10.1093/bioinformatics/bti431. View

Cemerski S, Das J, Locasale J, Arnold P, Giurisato E, Markiewicz M . The stimulatory potency of T cell antigens is influenced by the formation of the immunological synapse. Immunity. 2007; 26(3):345-55. PMC: 2763191. DOI: 10.1016/j.immuni.2007.01.013. View

Campi G, Varma R, Dustin M . Actin and agonist MHC-peptide complex-dependent T cell receptor microclusters as scaffolds for signaling. J Exp Med. 2005; 202(8):1031-6. PMC: 1373686. DOI: 10.1084/jem.20051182. View

Smith C, Joseph N, Rieger B, Lidke K . Fast, single-molecule localization that achieves theoretically minimum uncertainty. Nat Methods. 2010; 7(5):373-5. PMC: 2862147. DOI: 10.1038/nmeth.1449. View

Krutzik P, Nolan G . Intracellular phospho-protein staining techniques for flow cytometry: monitoring single cell signaling events. Cytometry A. 2003; 55(2):61-70. DOI: 10.1002/cyto.a.10072. View

Celada F, Seiden P . A computer model of cellular interactions in the immune system. Immunol Today. 1992; 13(2):56-62. DOI: 10.1016/0167-5699(92)90135-T. View

Yates A, Callard R, Stark J . Combining cytokine signalling with T-bet and GATA-3 regulation in Th1 and Th2 differentiation: a model for cellular decision-making. J Theor Biol. 2004; 231(2):181-96. DOI: 10.1016/j.jtbi.2004.06.013. View

10.

Cabantous S, Terwilliger T, Waldo G . Protein tagging and detection with engineered self-assembling fragments of green fluorescent protein. Nat Biotechnol. 2004; 23(1):102-7. DOI: 10.1038/nbt1044. View

11.

Li S, Armstrong C, Bertin N, Ge H, Milstein S, Boxem M . A map of the interactome network of the metazoan C. elegans. Science. 2004; 303(5657):540-3. PMC: 1698949. DOI: 10.1126/science.1091403. View

12.

Takahashi K, Ishikawa N, Sadamoto Y, Sasamoto H, Ohta S, Shiozawa A . E-Cell 2: multi-platform E-Cell simulation system. Bioinformatics. 2004; 19(13):1727-9. DOI: 10.1093/bioinformatics/btg221. View

13.

Burczynski M, Peterson R, Twine N, Zuberek K, Brodeur B, Casciotti L . Molecular classification of Crohn's disease and ulcerative colitis patients using transcriptional profiles in peripheral blood mononuclear cells. J Mol Diagn. 2006; 8(1):51-61. PMC: 1867573. DOI: 10.2353/jmoldx.2006.050079. View

14.

Spooner C, Cheng J, Pujadas E, Laslo P, Singh H . A recurrent network involving the transcription factors PU.1 and Gfi1 orchestrates innate and adaptive immune cell fates. Immunity. 2009; 31(4):576-86. PMC: 4373467. DOI: 10.1016/j.immuni.2009.07.011. View

15.

Chaussabel D, Tolouei Semnani R, McDowell M, Sacks D, Sher A, Nutman T . Unique gene expression profiles of human macrophages and dendritic cells to phylogenetically distinct parasites. Blood. 2003; 102(2):672-81. DOI: 10.1182/blood-2002-10-3232. View

16.

Tolar P, Sohn H, Pierce S . The initiation of antigen-induced B cell antigen receptor signaling viewed in living cells by fluorescence resonance energy transfer. Nat Immunol. 2005; 6(11):1168-76. DOI: 10.1038/ni1262. View

17.

Kruger M, Moser M, Ussar S, Thievessen I, Luber C, Forner F . SILAC mouse for quantitative proteomics uncovers kindlin-3 as an essential factor for red blood cell function. Cell. 2008; 134(2):353-64. DOI: 10.1016/j.cell.2008.05.033. View

18.

Kim J, White F . Quantitative analysis of phosphotyrosine signaling networks triggered by CD3 and CD28 costimulation in Jurkat cells. J Immunol. 2006; 176(5):2833-43. DOI: 10.4049/jimmunol.176.5.2833. View

19.

Karlas A, Machuy N, Shin Y, Pleissner K, Artarini A, Heuer D . Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication. Nature. 2010; 463(7282):818-22. DOI: 10.1038/nature08760. View

20.

Callard R, Hodgkin P . Modeling T- and B-cell growth and differentiation. Immunol Rev. 2007; 216:119-29. DOI: 10.1111/j.1600-065X.2006.00498.x. View