Mol2013 - Immune Signal Transduction in Leishmaniasis

Model Identifier
BIOMD0000000477
Short description
Created by The MathWorks, Inc. SimBiology tool, Version 3.3
Format
SBML
(L2V4)
Related Publication
-
Immune signal transduction in leishmaniasis from natural to artificial systems: role of feedback loop insertion.
- Mol M, Patole MS, Singh S
- Biochimica et biophysica acta , 1/ 2014 , Volume 1840 , pages: 71-79 , PubMed ID: 23994140
- National Centre for Cell Science, NCCS Complex, Ganeshkhind, Pune University Campus, Pune 411007, India.
- Modulated immune signal (CD14-TLR and TNF) in leishmaniasis can be linked to EGFR pathway involved in wound healing, through crosstalk points. This signaling network can be further linked to a synthetic gene circuit acting as a positive feedback loop to elicit a synchronized intercellular communication among the immune cells which may contribute to a better understanding of signaling dynamics in leishmaniasis.Network reconstruction with positive feedback loop, simulation (ODE 15s solver) and sensitivity analysis of CD14-TLR, TNF and EGFR was done in SimBiology (MATLAB 7.11.1). Cytoscape and adjacency matrix were used to calculate network topology. PCA was extracted by using sensitivity coefficient in MATLAB. Model reduction was done using time, flux and sensitivity score.Network has five crosstalk points: NIK, IκB-NFκB and MKK (4/7, 3/6, 1/2) which show high flux and sensitivity. PI3K in EGFR pathway shows high flux and sensitivity. PCA score was high for cytoplasmic ERK1/2, PI3K, Atk, STAT1/3 and nuclear JNK. Of the 125 parameters, 20% are crucial as deduced by model reduction.EGFR can be linked to CD14-TLR and TNF through the MAPK crosstalk points. These pathways may be controlled through Ras and Raf that lie upstream of signaling components ERK ½ (c) and JNK (n) that have a high PCA score via a synthetic gene circuit for activating cell-cell communication to elicit an inflammatory response. Also a disease resolving effect may be achieved through PI3K in the EGFR pathway.The reconstructed signaling network can be linked to a gene circuit with a positive feedback loop, for cell-cell communication resulting in synchronized response in the immune cell population, for disease resolving effect in leishmaniasis.
Contributors
administrator, Shailza Singh
Metadata information
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Curation status
Curated
Tags
Name | Description | Size | Actions |
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Model files |
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BIOMD0000000477_url.xml | SBML L2V4 representation of Mol2013 - Immune Signal Transduction in Leishmaniasis | 116.58 KB | Preview | Download |
Additional files |
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BIOMD0000000477.sci | Auto-generated Scilab file | 244.00 Bytes | Preview | Download |
BIOMD0000000477-biopax2.owl | Auto-generated BioPAX (Level 2) | 96.55 KB | Preview | Download |
BIOMD0000000477.vcml | Auto-generated VCML file | 150.49 KB | Preview | Download |
BIOMD0000000477-biopax3.owl | Auto-generated BioPAX (Level 3) | 160.70 KB | Preview | Download |
MODEL1308080000_figure5.cps | Reaction fluxes of signalling components that are at the crosstalk point and that show high PCA score. | 149.15 KB | Preview | Download |
BIOMD0000000477.png | Auto-generated Reaction graph (PNG) | 319.30 KB | Preview | Download |
BIOMD0000000477.m | Auto-generated Octave file | 40.11 KB | Preview | Download |
BIOMD0000000477_urn.xml | Auto-generated SBML file with URNs | 115.29 KB | Preview | Download |
BIOMD0000000477.xpp | Auto-generated XPP file | 22.34 KB | Preview | Download |
BIOMD0000000477.svg | Auto-generated Reaction graph (SVG) | 194.54 KB | Preview | Download |
BIOMD0000000477.pdf | Auto-generated PDF file | 506.51 KB | Preview | Download |
- Model originally submitted by : Shailza Singh
- Submitted: 08-Aug-2013 12:13:47
- Last Modified: 21-Dec-2018 17:21:27
Revisions
-
Version: 3
- Submitted on: 21-Dec-2018 17:21:27
- Submitted by: administrator
- With comment: Include the additional files provided by the submitter in the original submission: MODEL1308080000_figure5.cps
-
Version: 2
- Submitted on: 10-Oct-2014 12:11:26
- Submitted by: Shailza Singh
- With comment: Current version of Mol2013 - Immune Signal Transduction in Leishmaniasis
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Version: 1
- Submitted on: 08-Aug-2013 12:13:47
- Submitted by: Shailza Singh
- With comment: Original import of network
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Legends
: Variable used inside SBML models
: Variable used inside SBML models
Species
Species | Initial Concentration/Amount |
---|---|
mw3832f277 aef2 4f1d 87af abc2a3c1a7d5 Tyrosine-protein kinase JAK1 |
1.6 1E-9*mol |
mw8cc67de0 64e6 428f ab09 4c2825cc172c Tumor necrosis factor receptor superfamily member 1A |
1.3 1E-9*mol |
mw05469f51 73f7 4ba1 9f1a bce5fea143c2 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate |
1.45 1E-9*mol |
mwf20834c8 a115 460b 859c 4e3ca1ffd953 diglyceride |
0.9 1E-9*mol |
mwb4633da9 f9d6 4ad8 a7e5 da075c830e17 Protein kinase C alpha type ; Putative serine/threonine-protein kinase-like protein CCR3 |
1.5 1E-9*mol |
mw9bb804c9 3e4e 4684 9f6b 4e6f6706a58e Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha |
1.6 1E-9*mol |
mw9a5baf6d 0285 4ad3 9499 059c553d9cf6 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 ; cytokine-mediated signaling pathway |
1.6 1E-9*mol |
mw64453fc5 a275 4bba 84f0 2af249b31514 Tyrosine-protein kinase BTK |
1.2 1E-9*mol |
Reactions
Reactions | Rate | Parameters |
---|---|---|
mw280197c8_98de_43f0_bf01_0f332a1ab689 => mw3832f277_aef2_4f1d_87af_abc2a3c1a7d5; mw280197c8_98de_43f0_bf01_0f332a1ab689 | mw234b354b_eb7b_4af6_a678_9339f6b5eb8d*mw280197c8_98de_43f0_bf01_0f332a1ab689/(mw18baeb4d_ad18_4c22_95c4_2ada0f618c65+mw280197c8_98de_43f0_bf01_0f332a1ab689) | mw18baeb4d_ad18_4c22_95c4_2ada0f618c65=1.8 nanomole; mw234b354b_eb7b_4af6_a678_9339f6b5eb8d=0.01 nanomole/second |
mw8cc67de0_64e6_428f_ab09_4c2825cc172c => mw6ee00a71_ab68_454b_b1cd_60c1ebd19cfa; mw8cc67de0_64e6_428f_ab09_4c2825cc172c | mw6834a7ac_63c4_4741_b0fc_069c665f1de2*mw8cc67de0_64e6_428f_ab09_4c2825cc172c | mw6834a7ac_63c4_4741_b0fc_069c665f1de2=1.18 1/second |
mw05469f51_73f7_4ba1_9f1a_bce5fea143c2 => mwf20834c8_a115_460b_859c_4e3ca1ffd953; mw05469f51_73f7_4ba1_9f1a_bce5fea143c2 | mweaee0b65_7c40_4c9e_bd70_c5454eeb41fa*mw05469f51_73f7_4ba1_9f1a_bce5fea143c2/(mw84020ddc_e419_4aa4_ab12_e84989ad461d+mw05469f51_73f7_4ba1_9f1a_bce5fea143c2) | mweaee0b65_7c40_4c9e_bd70_c5454eeb41fa=0.9 nanomole/second; mw84020ddc_e419_4aa4_ab12_e84989ad461d=0.3 nanomole |
mwf20834c8_a115_460b_859c_4e3ca1ffd953 => mwb4633da9_f9d6_4ad8_a7e5_da075c830e17; mwf20834c8_a115_460b_859c_4e3ca1ffd953 | mw9d566811_669e_4b95_8452_c4853f54a2de*mwf20834c8_a115_460b_859c_4e3ca1ffd953 | mw9d566811_669e_4b95_8452_c4853f54a2de=0.35 1/second |
mwb4633da9_f9d6_4ad8_a7e5_da075c830e17 => mw7204ab72_2ee5_4b92_b420_2583dacc4343; mwb4633da9_f9d6_4ad8_a7e5_da075c830e17 | mw99befd62_975f_49e1_bfaf_22a482ce44ea*mwb4633da9_f9d6_4ad8_a7e5_da075c830e17/(mwb38e4258_82d9_4b48_8059_eccf9fd6f8e3+mwb4633da9_f9d6_4ad8_a7e5_da075c830e17) | mwb38e4258_82d9_4b48_8059_eccf9fd6f8e3=0.2 nanomole; mw99befd62_975f_49e1_bfaf_22a482ce44ea=1.2 nanomole/second |
mwb4633da9_f9d6_4ad8_a7e5_da075c830e17 => mw173d8585_5817_4b4c_932a_cf7d673680ac; mwb4633da9_f9d6_4ad8_a7e5_da075c830e17 | mwdeab2870_570e_4b2c_b73d_84c1ad8c2262*mwb4633da9_f9d6_4ad8_a7e5_da075c830e17/(mw4945db3d_e20c_4870_b96b_6fb98c4b12f6+mwb4633da9_f9d6_4ad8_a7e5_da075c830e17) | mw4945db3d_e20c_4870_b96b_6fb98c4b12f6=1.0 nanomole; mwdeab2870_570e_4b2c_b73d_84c1ad8c2262=1.0 nanomole/second |
mw280197c8_98de_43f0_bf01_0f332a1ab689 => mw9bb804c9_3e4e_4684_9f6b_4e6f6706a58e; mw280197c8_98de_43f0_bf01_0f332a1ab689 | mw78df1f4c_2a96_4d8f_a009_c19ba0ec406a*mw280197c8_98de_43f0_bf01_0f332a1ab689/(mw6a74caa7_9d44_449b_854b_c1678b36ac1d+mw280197c8_98de_43f0_bf01_0f332a1ab689) | mw6a74caa7_9d44_449b_854b_c1678b36ac1d=0.8 nanomole; mw78df1f4c_2a96_4d8f_a009_c19ba0ec406a=0.2 nanomole/second |
mw9bb804c9_3e4e_4684_9f6b_4e6f6706a58e => mw64453fc5_a275_4bba_84f0_2af249b31514; mw9bb804c9_3e4e_4684_9f6b_4e6f6706a58e | mw3690266b_c916_4ba1_a98a_b589dc75c1cd*mw9bb804c9_3e4e_4684_9f6b_4e6f6706a58e/(mwb69d510c_dcde_4bfb_9e4a_89954f6a7bf5+mw9bb804c9_3e4e_4684_9f6b_4e6f6706a58e) | mwb69d510c_dcde_4bfb_9e4a_89954f6a7bf5=1.5 nanomole; mw3690266b_c916_4ba1_a98a_b589dc75c1cd=0.8 nanomole/second |
mw280197c8_98de_43f0_bf01_0f332a1ab689 => mw9a5baf6d_0285_4ad3_9499_059c553d9cf6; mw280197c8_98de_43f0_bf01_0f332a1ab689 | mwb3751ef8_2226_4ec3_9ac9_f92f5771a1a4*mw280197c8_98de_43f0_bf01_0f332a1ab689/(mw244e346b_4442_45db_864e_0442ceca94d1+mw280197c8_98de_43f0_bf01_0f332a1ab689) | mw244e346b_4442_45db_864e_0442ceca94d1=0.5 nanomole; mwb3751ef8_2226_4ec3_9ac9_f92f5771a1a4=2.0E-4 nanomole/second |
mw9a5baf6d_0285_4ad3_9499_059c553d9cf6 => mw05469f51_73f7_4ba1_9f1a_bce5fea143c2; mw9a5baf6d_0285_4ad3_9499_059c553d9cf6 | mw18e075a4_dde4_42be_9315_e0e90d461b99*mw9a5baf6d_0285_4ad3_9499_059c553d9cf6/(mw6d4dc2a5_6fe8_4d80_93f4_b9f438b6eb0e+mw9a5baf6d_0285_4ad3_9499_059c553d9cf6) | mw6d4dc2a5_6fe8_4d80_93f4_b9f438b6eb0e=1.0 nanomole; mw18e075a4_dde4_42be_9315_e0e90d461b99=0.6 nanomole/second |
mwb4633da9_f9d6_4ad8_a7e5_da075c830e17 => mw32c21c39_237b_4d4c_bb5d_117cb30ce68a; mwb4633da9_f9d6_4ad8_a7e5_da075c830e17 | mw0f1ee85e_95a3_42c7_94ae_71f36061aaf0*mwb4633da9_f9d6_4ad8_a7e5_da075c830e17/(mw933afd80_4eff_4c6c_967b_d15b2244e55d+mwb4633da9_f9d6_4ad8_a7e5_da075c830e17) | mw933afd80_4eff_4c6c_967b_d15b2244e55d=1.0 nanomole; mw0f1ee85e_95a3_42c7_94ae_71f36061aaf0=1.0 nanomole/second |
Curator's comment:
(added: 10 Sep 2013, 15:50:35, updated: 10 Sep 2013, 15:50:35)
(added: 10 Sep 2013, 15:50:35, updated: 10 Sep 2013, 15:50:35)
The paper has a Flux V/s Sensitivity bar chart (figure 5) of the signalling components that are at the crosstalk points and those that show high PCA (Principal component analysis) score. Here, time-course of the fluxes of the corresponding components (components at the crosstalk points and the components that show high PCA score) of figure 5 of the papers is produced. Simulation was done using Copasi v4.10 (Build 55). The plots were generated using Gnuplot.