- Oral presentation
- Open Access
Metabolic Network Analysis: Implication And Application
BMC Bioinformatics volume 6, Article number: S12 (2005)
Pathway Alignment Tool (PAT) executables are available upon request; Pathway Hunter Tool (PHT) is available on http://www.pht.uni-koeln.de
Local metabolic demand and supply regulate network components and control their activity globally. The use of metabolite structural information to calculate the shortest path generates valid biochemical connectivity . We introduce a new concept of "load points" for identifying and empirically ranking the important points (metabolites/enzymes) in the network. The load point analysis provides a global insight into the metabolic network, which cannot be obtained from connectivity information or metabolic concentration data. We propose a new computational model based on extended graph theory to find "Choke point (CP)" and "Load point" enzymes (enzymes that uniquely consume or produce a certain metabolite in the network) . Identifying such enzymes is the key to network-based potential drug targeting . We obtained few potential drug targets based on the "choke point" analysis of the network in the malarial parasite Plasmodium falciparum and pathogenic bacterium Helicobacter pylori. A comparative study was performed between human network and pathogenic network. Each potential target is ranked by its load value and results were divided in sub-classes based on the homology. This was done in order to make our results biologically more meaningful. Since this method screens the entire pathogenic network, it is more valuable than other existing methods which report the potential target by looking at specific pathways or certain biological activity like reverse transcriptase in case of HIV. These modules are implemented in Pathway Hunter Tool (PHT) and available via web.
A new algorithm to perform metabolic pathway alignment (based on the shortest path) highlights the conserved (isoenzmes) and variable connectivity (alternate paths) in various genomes. Gibbs free energy (G°) §, enzyme connectivity and enzyme occurrence matrix was used to rank the aligned pathways. Gaps (insertion and deletion) can be allowed during the alignment for obtaining more flexible results since most of the annotated networks have missing links. This method highlights the application and implication of metabolic networks [5, 6] and it also suggests enzymes for "hole filling" in the metabolic network. This module is implemented in Pathway Alignment Tool (PAT).
§For bringing the molecules into the correct standard state at pH 7, see: ChemAxon Ltd., Máramaros köz 3/a, Budapest, 1037 Hungary.
Tel.: +361 4532658, e-mail: email@example.com, http://www.chemaxon.com
Rahman SA, Advani P, Schunk R, Schrader R, Schomburg D: Metabolic pathway analysis web service (Pathway Hunter Tool at CUBIC). Bioinformatics 2005,21(7):1189–1193. 10.1093/bioinformatics/bti116
Rahman SA, Schrader R, Schomburg D: Observing Local and Global Properties of Metabolic Pathways: "Load Points" and "Choke Points" in the Metabolic Networks. Communicated
Yeh I, Hanekamp T, Tsoka S, Karp PD, Altman RB: Computational analysis of Plasmodium falciparum metabolism: organizing genomic information to facilitate drug discovery. Genome Res 2004,14(5):917–924. 10.1101/gr.2050304
Mavrovouniotis ML: Estimation of standard Gibbs energy changes of biotransformations. J Biol Chem 1991,266(22):14440–14445.
Dandekar T, Schuster S, Snel B, Huynen M, Bork P: Pathway alignment: application to the comparative analysis of glycolytic enzymes. Biochem J 1999,343(Pt 1):115–124. 10.1042/0264-6021:3430115
Kelley BP, Sharan R, Karp RM, Sittler T, Root DE, Stockwell BR, Ideker T: Conserved pathways within bacteria and yeast as revealed by global protein network alignment. Proc Natl Acad Sci U S A 2003,100(20):11394–11399. 10.1073/pnas.1534710100
About this article
Cite this article
Rahman, S.A., Jonnalagadda, P.S., Padiadpu, J. et al. Metabolic Network Analysis: Implication And Application. BMC Bioinformatics 6, S12 (2005). https://doi.org/10.1186/1471-2105-6-S3-S12
- metabolic pathway alignment
- load point
- choke point
- drug target
- pathway analysis
- conserved pathways
- alternate paths
- shortest path