Modelovanje metaboličkih mreža — разлика између измена

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Верзија на датум 18. април 2018. у 01:07

Metabolička mreža prikazuje interakcije imeđu enzima i metabolita u ciklusu mlečne kiseline biljke Arabidopsis thaliana. Enzimi i metaboliti su označeni crvenim tačkama, a interakcije među njima linijama.
Model metabolička mreža za bakteriju Escherichia coli.

Rekonstrukcija i simulacija metaboličkih mreža omogućava iscrpni uvidi u molekularne mehanizme specifičnih organizama. In particular, these models correlate the genome with molecular physiology.[1] A reconstruction breaks down metabolic pathways (such as glycolysis and the citric acid cycle) into their respective reactions and enzymes, and analyzes them within the perspective of the entire network. In simplified terms, a reconstruction collects all of the relevant metabolic information of an organism and compiles it in a mathematical model. Validation and analysis of reconstructions can allow identification of key features of metabolism such as growth yield, resource distribution, network robustness, and gene essentiality. This knowledge can then be applied to create novel biotechnology.

In general, the process to build a reconstruction is as follows:

  1. Draft a reconstruction
  2. Refine the model
  3. Convert model into a mathematical/computational representation
  4. Evaluate and debug model through experimentation

Metabolička rekonstrukcija na genomskoj skali

A metabolic reconstruction provides a highly mathematical, structured platform on which to understand the systems biology of metabolic pathways within an organism.[2] The integration of biochemical metabolic pathways with rapidly available, unannotated genome sequences has developed what are called genome-scale metabolic models. Simply put, these models correspond metabolic genes with metabolic pathways. In general, the more information about physiology, biochemistry and genetics is available for the target organism, the better the predictive capacity of the reconstructed models. Mechanically speaking, the process of reconstructing prokaryotic and eukaryotic metabolic networks is essentially the same. Having said this, eukaryote reconstructions are typically more challenging because of the size of genomes, coverage of knowledge, and the multitude of cellular compartments.[2] The first genome-scale metabolic model was generated in 1995 for Haemophilus influenzae.[3] The first multicellular organism, C. elegans, was reconstructed in 1998.[4] Since then, many reconstructions have been formed. For a list of reconstructions that have been converted into a model and experimentally validated, see http://sbrg.ucsd.edu/InSilicoOrganisms/OtherOrganisms.

Organizam Gena u genomu Gena u modelu Reakcije Metaboliti Datum rekonstrukcije Reference
Haemophilus influenzae 1,775 296 488 343 jun 1999 [3]
Escherichia coli 4,405 660 627 438 maj 2000 [5]
Saccharomyces cerevisiae 6,183 708 1,175 584 februar 2003 [6]
Mus musculus 28,287 473 1220 872 januar 2005 [7]
Homo sapiens 21,090[8] 3,623 3,673 -- januar 2007 [9]
Mycobacterium tuberculosis 4,402 661 939 828 jun 2007 [10]
Bacillus subtilis 4,114 844 1,020 988 septembar 2007 [11]
Synechocystis sp. PCC6803 3,221 633 831 704 oktobar 2008 [12]
Salmonella typhimurium 4,489 1,083 1,087 774 april 2009 [13]
Arabidopsis thaliana 27,379 1,419 1,567 1,748 februar 2010 [14]

Reference

  1. ^ Franke; Siezen, Teusink (2005). „Reconstructing the metabolic network of a bacterium from its genome.”. Trends in Microbiology. 13 (11): 550—558. PMID 16169729. doi:10.1016/j.tim.2005.09.001. 
  2. ^ а б Thiele, Ines; Bernhard Ø Palsson (јануар 2010). „A protocol for generating a high-quality genome-scale metabolic reconstruction”. Nature Protocols. 5 (1): 93—121. PMC 3125167 Слободан приступ. PMID 20057383. doi:10.1038/nprot.2009.203. 
  3. ^ а б Fleischmann, R. D.; Adams, M. D.; White, O; Clayton, R. A.; Kirkness, E. F.; Kerlavage, A. R.; Bult, C. J.; Tomb, J. F.; Dougherty, B. A.; Merrick, J. M. (1995). „Whole-genome random sequencing and assembly of Haemophilus influenzae Rd”. Science. 269 (1995): 496—512. PMID 7542800. doi:10.1126/science.7542800. 
  4. ^ The C. elegans Sequencing Consortium (1998). „Genome Sequence of the Nematode C. elegans: A Platform for Investigating Biology”. Science. 282 (5396): 2012—2018. PMID 9851916. doi:10.1126/science.282.5396.2012. 
  5. ^ Edwards, J. S.; et al. (мај 2000). „The Escherichia coli MG1655 in silico metabolic genotype: Its definition, characteristics, and capabilities”. PNAS. 97 (10): 5528—5533. PMC 25862 Слободан приступ. PMID 10805808. doi:10.1073/pnas.97.10.5528. 
  6. ^ Förster J, Famili I, Fu P, Palsson BØ, Nielsen J (фебруар 2003). „Genome-Scale Reconstruction of the Saccharomyces cerevisiae Metabolic Network”. Genome Research. 13 (2): 244—253. PMC 420374 Слободан приступ. PMID 12566402. doi:10.1101/gr.234503. 
  7. ^ Sheikh, Kashif; et al. (јануар 2005). „Modeling Hybridoma Cell Metabolism Using a Generic Genome-Scale Metabolic Model of Mus musculus”. Biotechnology Resources. 21 (1): 112—121. doi:10.1021/bp0498138. 
  8. ^ Romero, Pedro; Jonathan Wagg; Michelle L Green; Dale Kaiser; Markus Krummenacker; Peter D Karp (јун 2004). „Computational prediction of human metabolic pathways from the complete human genome”. Genome Biology. 6 (1): R2. PMC 549063 Слободан приступ. PMID 15642094. doi:10.1186/gb-2004-6-1-r2. 
  9. ^ Duarte, N. C.; et al. (јануар 2007). „Global reconstruction of the human metabolic network based on genomic and bibliomic data”. PNAS. 104 (6): 1777—1782. PMC 1794290 Слободан приступ. PMID 17267599. doi:10.1073/pnas.0610772104. 
  10. ^ Jamshidi, Neema; B. O. Palsson (јун 2007). „Investigating the metabolic capabilities of Mycobacterium tuberculosis H”. BMC Systems Biology. 1: 26. PMC 1925256 Слободан приступ. PMID 17555602. doi:10.1186/1752-0509-1-26. 
  11. ^ Oh, Y.-K.; et al. (септембар 2007). „Genome-scale Reconstruction of Metabolic Network in Bacillus subtilis Based on High-throughput Phenotyping and Gene Essentiality Data”. Journal of Biological Chemistry. 282 (39): 28791—28799. PMID 17573341. doi:10.1074/jbc.M703759200. 
  12. ^ Fu, Pengcheng (октобар 2008). „Genome-scale modeling of Synechocystis sp. PCC 6803 and prediction of pathway insertion”. Journal of Chemical Technology and Biotechnology. 84 (4): 473—483. doi:10.1002/jctb.2065. 
  13. ^ Raghunathan, Anu; et al. (април 2009). „Constraint-based analysis of metabolic capacity of Salmonella typhimurium during host-pathogen interaction”. BMC Systems Biology. 3: 38. PMC 2678070 Слободан приступ. PMID 19356237. doi:10.1186/1752-0509-3-38. 
  14. ^ de Oliveira Dal'Molin, C. G.; Quek, L.-E.; Palfreyman, R. W.; Brumbley, S. M.; Nielsen, L. K. (фебруар 2010). „AraGEM, a Genome-Scale Reconstruction of the Primary Metabolic Network in Arabidopsis”. Plant Physiology. 152 (2): 579—589. PMC 2815881 Слободан приступ. PMID 20044452. doi:10.1104/pp.109.148817. 

Literatura

  1. Overbeek R, Larsen N, Walunas T, D'Souza M, Pusch G, Selkov Jr, Liolios K, Joukov V, Kaznadzey D, Anderson I, Bhattacharyya A, Burd H, Gardner W, Hanke P, Kapatral V, Mikhailova N, Vasieva O, Osterman A, Vonstein V, Fonstein M, Ivanova N, Kyrpides N. (2003) The ERGO genome analysis and discovery system. Nucleic Acids Res. 31(1):164-71
  2. Whitaker, J.W., Letunic, I., McConkey, G.A. and Westhead, D.R. metaTIGER: a metabolic evolution resource. Nucleic Acids Res. 2009 37: D531-8.

Spoljašnje veze

Преузето из „https://sr.wikipedia.org/w/index.php?title=Modelovanje_metaboličkih_mreža&oldid=19811293”