A methodology for performing global uncertainty and sensitivity analysis in systems biology.

Simeone Marino, Ian B Hogue, Christian J Ray, Denise E Kirschner
Author Information
  1. Simeone Marino: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA.

Abstract

Accuracy of results from mathematical and computer models of biological systems is often complicated by the presence of uncertainties in experimental data that are used to estimate parameter values. Current mathematical modeling approaches typically use either single-parameter or local sensitivity analyses. However, these methods do not accurately assess uncertainty and sensitivity in the system as, by default, they hold all other parameters fixed at baseline values. Using techniques described within we demonstrate how a multi-dimensional parameter space can be studied globally so all uncertainties can be identified. Further, uncertainty and sensitivity analysis techniques can help to identify and ultimately control uncertainties. In this work we develop methods for applying existing analytical tools to perform analyses on a variety of mathematical and computer models. We compare two specific types of global sensitivity analysis indexes that have proven to be among the most robust and efficient. Through familiar and new examples of mathematical and computer models, we provide a complete methodology for performing these analyses, in both deterministic and stochastic settings, and propose novel techniques to handle problems encountered during these types of analyses.

References

  1. Risk Anal. 2002 Jun;22(3):591-622 [PMID: 12088236]
  2. Science. 1990 Dec 7;250(4986):1359-64 [PMID: 2255906]
  3. J Immunol. 2004 Jul 1;173(1):494-506 [PMID: 15210810]
  4. Infect Immun. 2008 Jul;76(7):3221-32 [PMID: 18443099]
  5. Regul Toxicol Pharmacol. 1994 Aug;20(1 Pt 1):15-36 [PMID: 7838990]
  6. Math Biosci Eng. 2007 Apr;4(2):261-88 [PMID: 17658927]
  7. J Theor Biol. 2004 Dec 7;231(3):357-76 [PMID: 15501468]
  8. Chem Rev. 2005 Jul;105(7):2811-28 [PMID: 16011325]
  9. Immunol Rev. 2007 Apr;216:93-118 [PMID: 17367337]
  10. Math Biosci. 1993 Mar;114(1):81-125 [PMID: 8096155]
  11. Theor Biol Med Model. 2008 Feb 27;5:4 [PMID: 18304361]
  12. J Theor Biol. 2004 Apr 21;227(4):463-86 [PMID: 15038983]
  13. J Theor Biol. 2008 Feb 21;250(4):732-51 [PMID: 18068193]

Grants

  1. R01 HL068526-03/NHLBI NIH HHS
  2. R01 HL068526-02/NHLBI NIH HHS
  3. R01 HL072682-05/NHLBI NIH HHS
  4. R01 HL072682-02/NHLBI NIH HHS
  5. R01 LM009027-02/NLM NIH HHS
  6. R01 HL068526-05/NHLBI NIH HHS
  7. R01 HL072682-04/NHLBI NIH HHS
  8. T32 GM007544/NIGMS NIH HHS
  9. R01 HL068526/NHLBI NIH HHS
  10. LM 009027/NLM NIH HHS
  11. HL68526/NHLBI NIH HHS
  12. R01 LM009027-01/NLM NIH HHS
  13. R01 HL072682-01/NHLBI NIH HHS
  14. R33 HL092853-01/NHLBI NIH HHS
  15. R01 LM009027/NLM NIH HHS
  16. R33 HL092853/NHLBI NIH HHS
  17. R01 HL072682/NHLBI NIH HHS
  18. R01 LM009027-03/NLM NIH HHS
  19. R01 HL068526-04/NHLBI NIH HHS
  20. R01 HL068526-01/NHLBI NIH HHS
  21. R01 HL072682-03/NHLBI NIH HHS

MeSH Term

Computational Biology
Computer Simulation
Models, Statistical
Numerical Analysis, Computer-Assisted
Sensitivity and Specificity
Systems Biology
Uncertainty

Word Cloud

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