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Extended CADLIVE: a novel graphical notation for design of biochemical network maps and computational pathway analysis.

Kurata H, Inoue K, Maeda K, Masaki K, Shimokawa Y, Zhao Q - Nucleic Acids Res. (2007)

Bottom Line: Furthermore, we developed a pathway search module for virtual knockout mutants as a built-in application of CADLIVE.This module analyzes gene function in the same way as molecular genetics, which simulates a change in mutant phenotypes or confirms the validity of the network map.The extended CADLIVE with the newly proposed notation is demonstrated to be feasible for computational simulation and analysis.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, Iizuka, 820-8502, Fukuoka, Japan. kurata@bio.kyutech.ac.jp

ABSTRACT
Biochemical network maps are helpful for understanding the mechanism of how a collection of biochemical reactions generate particular functions within a cell. We developed a new and computationally feasible notation that enables drawing a wide resolution map from the domain-level reactions to phenomenological events and implemented it as the extended GUI network constructor of CADLIVE (Computer-Aided Design of LIVing systEms). The new notation presents 'Domain expansion' for proteins and RNAs, 'Virtual reaction and nodes' that are responsible for illustrating domain-based interaction and 'InnerLink' that links real complex nodes to virtual nodes to illustrate the exact components of the real complex. A modular box is also presented that packs related reactions as a module or a subnetwork, which gives CADLIVE a capability to draw biochemical maps in a hierarchical modular architecture. Furthermore, we developed a pathway search module for virtual knockout mutants as a built-in application of CADLIVE. This module analyzes gene function in the same way as molecular genetics, which simulates a change in mutant phenotypes or confirms the validity of the network map. The extended CADLIVE with the newly proposed notation is demonstrated to be feasible for computational simulation and analysis.

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A biochemical network map of the mammalian translation initiation system. This map is drawn by the extended CADLIVE GUI editor.
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Figure 5: A biochemical network map of the mammalian translation initiation system. This map is drawn by the extended CADLIVE GUI editor.

Mentions: A biochemical network map in a mammalian translation initiation system is successfully drawn at the domain level as shown in Figure 5. An mRNA is expanded into the cap structure, initiation site and poly(A) tail. The complex (filled circle) 〈1〉 points to the virtual node (white circle) through the InnerLink arrow, indicating that the cap of the mRNA binds the 40S ribosome complex with eIF3:eIF1A and the Met-tRNAi:eIF2:GTP. The complex 〈2〉 points to the virtual node through InnerLink, indicating that the initiation site of the mRNA binds the 40S complex with eIF3:eIF1A and Met-tRNAi:eIF2:GTP. The complex 〈3〉 is linked to the virtual node by InnerLink, indicating that the complex consists of 40S, 60S, the initiation site of the mRNA and Met-tRNAi. This initiation complex is produced by eIF5. The protein complex of eIF4F 〈4〉 has the eIF4E and eIF4G subunits. These subunits are drawn in the same manner as the domain expansion method. The modified molecule of eIF4-P 〈5〉 points to the virtual node by InnerLink, indicating that the subunit eIF4E is phosphorylated. The binding complex of eIF4:BP 〈6〉 is linked to the virtual node by InnerLink, indicating that the eIF4E subunit binds to BP. The protein complex of eIF2 is expanded into three subunits: eIF2α, eIF2β and eIF2γ. The modified protein of eIF2-P 〈7〉 points to the virtual node by InnerLink, indicating that the serine 51 site of the eIF2α subunit is phosphorylated by GCN2. The GCN2 protein 〈8〉 has two domains: a kinase domain and RNA-binding domain. The phosphorylation activity of GCN2 is activated by the complex 〈9〉, which is linked to the virtual node by InnerLink, indicating that the tRNA binds to the binding domain of GCN2.Figure 5.


Extended CADLIVE: a novel graphical notation for design of biochemical network maps and computational pathway analysis.

Kurata H, Inoue K, Maeda K, Masaki K, Shimokawa Y, Zhao Q - Nucleic Acids Res. (2007)

A biochemical network map of the mammalian translation initiation system. This map is drawn by the extended CADLIVE GUI editor.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2175333&req=5

Figure 5: A biochemical network map of the mammalian translation initiation system. This map is drawn by the extended CADLIVE GUI editor.
Mentions: A biochemical network map in a mammalian translation initiation system is successfully drawn at the domain level as shown in Figure 5. An mRNA is expanded into the cap structure, initiation site and poly(A) tail. The complex (filled circle) 〈1〉 points to the virtual node (white circle) through the InnerLink arrow, indicating that the cap of the mRNA binds the 40S ribosome complex with eIF3:eIF1A and the Met-tRNAi:eIF2:GTP. The complex 〈2〉 points to the virtual node through InnerLink, indicating that the initiation site of the mRNA binds the 40S complex with eIF3:eIF1A and Met-tRNAi:eIF2:GTP. The complex 〈3〉 is linked to the virtual node by InnerLink, indicating that the complex consists of 40S, 60S, the initiation site of the mRNA and Met-tRNAi. This initiation complex is produced by eIF5. The protein complex of eIF4F 〈4〉 has the eIF4E and eIF4G subunits. These subunits are drawn in the same manner as the domain expansion method. The modified molecule of eIF4-P 〈5〉 points to the virtual node by InnerLink, indicating that the subunit eIF4E is phosphorylated. The binding complex of eIF4:BP 〈6〉 is linked to the virtual node by InnerLink, indicating that the eIF4E subunit binds to BP. The protein complex of eIF2 is expanded into three subunits: eIF2α, eIF2β and eIF2γ. The modified protein of eIF2-P 〈7〉 points to the virtual node by InnerLink, indicating that the serine 51 site of the eIF2α subunit is phosphorylated by GCN2. The GCN2 protein 〈8〉 has two domains: a kinase domain and RNA-binding domain. The phosphorylation activity of GCN2 is activated by the complex 〈9〉, which is linked to the virtual node by InnerLink, indicating that the tRNA binds to the binding domain of GCN2.Figure 5.

Bottom Line: Furthermore, we developed a pathway search module for virtual knockout mutants as a built-in application of CADLIVE.This module analyzes gene function in the same way as molecular genetics, which simulates a change in mutant phenotypes or confirms the validity of the network map.The extended CADLIVE with the newly proposed notation is demonstrated to be feasible for computational simulation and analysis.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, Iizuka, 820-8502, Fukuoka, Japan. kurata@bio.kyutech.ac.jp

ABSTRACT
Biochemical network maps are helpful for understanding the mechanism of how a collection of biochemical reactions generate particular functions within a cell. We developed a new and computationally feasible notation that enables drawing a wide resolution map from the domain-level reactions to phenomenological events and implemented it as the extended GUI network constructor of CADLIVE (Computer-Aided Design of LIVing systEms). The new notation presents 'Domain expansion' for proteins and RNAs, 'Virtual reaction and nodes' that are responsible for illustrating domain-based interaction and 'InnerLink' that links real complex nodes to virtual nodes to illustrate the exact components of the real complex. A modular box is also presented that packs related reactions as a module or a subnetwork, which gives CADLIVE a capability to draw biochemical maps in a hierarchical modular architecture. Furthermore, we developed a pathway search module for virtual knockout mutants as a built-in application of CADLIVE. This module analyzes gene function in the same way as molecular genetics, which simulates a change in mutant phenotypes or confirms the validity of the network map. The extended CADLIVE with the newly proposed notation is demonstrated to be feasible for computational simulation and analysis.

Show MeSH