Display options
Share it on

Front Microbiol. 2016 Jun 17;7:907. doi: 10.3389/fmicb.2016.00907. eCollection 2016.

From DNA to FBA: How to Build Your Own Genome-Scale Metabolic Model.

Frontiers in microbiology

Daniel A Cuevas, Janaka Edirisinghe, Chris S Henry, Ross Overbeek, Taylor G O'Connell, Robert A Edwards

Affiliations

  1. Computational Science Research Center, San Diego State University, San Diego CA, USA.
  2. Mathematics and Computer Science Division, Argonne National Laboratory, Argonne IL, USA.
  3. Fellowship for Interpretation of Genomes, Burr Ridge IL, USA.
  4. Biological and Medical Informatics Research Center, San Diego State University, San Diego CA, USA.
  5. Computational Science Research Center, San Diego State University, San DiegoCA, USA; Biological and Medical Informatics Research Center, San Diego State University, San DiegoCA, USA; Department of Computer Science, San Diego State University, San DiegoCA, USA; Department of Biology, San Diego State University, San DiegoCA, USA.

PMID: 27379044 PMCID: PMC4911401 DOI: 10.3389/fmicb.2016.00907

Abstract

Microbiological studies are increasingly relying on in silico methods to perform exploration and rapid analysis of genomic data, and functional genomics studies are supplemented by the new perspectives that genome-scale metabolic models offer. A mathematical model consisting of a microbe's entire metabolic map can be rapidly determined from whole-genome sequencing and annotating the genomic material encoded in its DNA. Flux-balance analysis (FBA), a linear programming technique that uses metabolic models to predict the phenotypic responses imposed by environmental elements and factors, is the leading method to simulate and manipulate cellular growth in silico. However, the process of creating an accurate model to use in FBA consists of a series of steps involving a multitude of connections between bioinformatics databases, enzyme resources, and metabolic pathways. We present the methodology and procedure to obtain a metabolic model using PyFBA, an extensible Python-based open-source software package aimed to provide a platform where functional annotations are used to build metabolic models (http://linsalrob.github.io/PyFBA). Backed by the Model SEED biochemistry database, PyFBA contains methods to reconstruct a microbe's metabolic map, run FBA upon different media conditions, and gap-fill its metabolism. The extensibility of PyFBA facilitates novel techniques in creating accurate genome-scale metabolic models.

Keywords: flux-balance analysis; genome annotation; in silico modeling; metabolic modeling; metabolic reconstruction; model SEED

References

  1. Bioinformatics. 2004 Aug 4;20 Suppl 1:i178-85 - PubMed
  2. Nature. 2015 Jan 15;517(7534):369-72 - PubMed
  3. J Vis Exp. 2015 Jun 11;(100):e52854 - PubMed
  4. Biosystems. 2011 Aug;105(2):162-8 - PubMed
  5. Sci Rep. 2015 Feb 10;5:8365 - PubMed
  6. Trends Biotechnol. 2003 Apr;21(4):162-9 - PubMed
  7. Curr Opin Biotechnol. 2003 Oct;14(5):491-6 - PubMed
  8. Proc Natl Acad Sci U S A. 2010 Oct 12;107(41):17845-50 - PubMed
  9. Bioinformatics. 2014 Jul 15;30(14):2068-9 - PubMed
  10. Nucleic Acids Res. 2014 Jan;42(Database issue):D206-14 - PubMed
  11. BMC Bioinformatics. 2011 Jan 22;12:28 - PubMed
  12. Nucleic Acids Res. 2014 Jan;42(Database issue):D581-91 - PubMed
  13. BMC Syst Biol. 2013 Aug 08;7:74 - PubMed
  14. Brief Bioinform. 2014 Jan;15(1):108-22 - PubMed
  15. Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W455-9 - PubMed
  16. Trends Biochem Sci. 1993 Jan;18(1):13-20 - PubMed
  17. BMC Syst Biol. 2008 Jun 29;2:55 - PubMed
  18. Methods Mol Biol. 2015;1231:177-89 - PubMed
  19. Mol Syst Biol. 2013 Oct 01;9:693 - PubMed
  20. Nucleic Acids Res. 2004 Jan 1;32(Database issue):D277-80 - PubMed
  21. Genome Biol. 2012 Nov 29;13(11):R111 - PubMed
  22. BMC Bioinformatics. 2007 Apr 26;8:139 - PubMed
  23. Bioinformatics. 2005 Sep 15;21(18):3674-6 - PubMed
  24. BMC Bioinformatics. 2007 Jun 20;8:212 - PubMed
  25. BMC Genomics. 2008 Feb 08;9:75 - PubMed
  26. Nucleic Acids Res. 2002 Jan 1;30(1):47-9 - PubMed
  27. Brief Bioinform. 2006 Jun;7(2):140-50 - PubMed
  28. Nat Protoc. 2011 Aug 04;6(9):1290-307 - PubMed
  29. Biotechnol Bioeng. 2003 Jun 20;82(6):670-7 - PubMed
  30. Methods Mol Biol. 2013;985:17-45 - PubMed
  31. Nucleic Acids Res. 2000 Jan 1;28(1):123-5 - PubMed
  32. Biotechnol Prog. 2001 Sep-Oct;17(5):791-7 - PubMed
  33. Environ Microbiol. 2014 Jan;16(1):49-59 - PubMed
  34. Nucleic Acids Res. 2014 Jan;42(Database issue):D459-71 - PubMed
  35. PLoS Comput Biol. 2006 Jul 7;2(7):e72 - PubMed
  36. Nucleic Acids Res. 2003 Jul 1;31(13):3784-8 - PubMed
  37. Microbiol Rev. 1994 Mar;58(1):71-93 - PubMed
  38. J Exp Bot. 2012 Mar;63(6):2247-58 - PubMed
  39. Nat Biotechnol. 2010 Mar;28(3):245-8 - PubMed
  40. PLoS Comput Biol. 2011 Mar;7(3):e1001116 - PubMed
  41. Nucleic Acids Res. 2012 Jan;40(Database issue):D109-14 - PubMed
  42. Nucleic Acids Res. 2003 Jan 1;31(1):164-71 - PubMed
  43. Proc Natl Acad Sci U S A. 2000 May 9;97(10):5528-33 - PubMed
  44. Environ Microbiol. 2002 Mar;4(3):133-40 - PubMed
  45. Brief Bioinform. 2009 Jul;10(4):435-49 - PubMed
  46. PLoS Comput Biol. 2009 Mar;5(3):e1000308 - PubMed
  47. Mol Syst Biol. 2014 Jul 01;10:735 - PubMed
  48. Nat Biotechnol. 2000 Nov;18(11):1147-50 - PubMed
  49. PLoS Comput Biol. 2014 Oct 16;10(10):e1003882 - PubMed
  50. BMC Bioinformatics. 2010 Sep 29;11:489 - PubMed
  51. BMC Syst Biol. 2014 Sep 18;8:110 - PubMed

Publication Types