Mol2013 - Immune Signal Transduction in Leishmaniasis

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Created by The MathWorks, Inc. SimBiology tool, Version 3.3

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.
administrator, Shailza Singh

Metadata information

BioModels Database MODEL1308080000
BioModels Database BIOMD0000000477
PubMed 23994140
Taxonomy Homo sapiens
Human Disease Ontology leishmaniasis

Curation status

Name Description Size Actions

Model files

BIOMD0000000477_url.xml SBML L2V4 representation of Mol2013 - Immune Signal Transduction in Leishmaniasis 116.58 KB Preview | Download

Additional files

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
  • Version: 3 public model Download this version
    • 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 public model Download this version
    • Submitted on: 10-Oct-2014 12:11:26
    • Submitted by: Shailza Singh
    • With comment: Current version of Mol2013 - Immune Signal Transduction in Leishmaniasis
  • Version: 1 public model Download this version
    • Submitted on: 08-Aug-2013 12:13:47
    • Submitted by: Shailza Singh
    • With comment: Original import of network

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

: Variable used inside SBML models

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

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 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)
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.