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.
Shailza Singh, administrator

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.pdf Auto-generated PDF file 506.51 KB Preview | Download
BIOMD0000000477.sci Auto-generated Scilab file 244.00 Bytes Preview | Download
BIOMD0000000477-biopax3.owl Auto-generated BioPAX (Level 3) 160.70 KB Preview | Download
BIOMD0000000477.png Auto-generated Reaction graph (PNG) 319.30 KB Preview | Download
BIOMD0000000477.svg Auto-generated Reaction graph (SVG) 194.54 KB Preview | Download
BIOMD0000000477.vcml Auto-generated VCML file 150.49 KB Preview | Download
BIOMD0000000477_urn.xml Auto-generated SBML file with URNs 115.29 KB Preview | Download
BIOMD0000000477-biopax2.owl Auto-generated BioPAX (Level 2) 96.55 KB Preview | Download
BIOMD0000000477.m Auto-generated Octave file 40.11 KB Preview | Download
BIOMD0000000477.xpp Auto-generated XPP file 22.34 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

  • 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
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
mw32c21c39 237b 4d4c bb5d 117cb30ce68a

RAF proto-oncogene serine/threonine-protein kinase
1.2 1E-9*mol
mw3832f277 aef2 4f1d 87af abc2a3c1a7d5

Tyrosine-protein kinase JAK1
1.6 1E-9*mol
mw13651143 feb5 49a5 adab 9105c2647446

Signal transducer and activator of transcription 1-alpha/beta
1.1 1E-9*mol
mw8a358487 b18b 42df a646 cd75eb5bfcc2

Nuclear factor NF-kappa-B p105 subunit
0.2 1E-9*mol
mwd9e7a9b9 6f1b 4bbc afa5 6cb192b62ce8

Mitogen-activated protein kinase 8
0.6 1E-9*mol
mwfed5a135 c91b 4d20 91b2 3a61723544dd

Transcription factor AP-1
0.91 1E-9*mol
mw97345a67 a8e8 42aa 8e62 69e9d2b6cf45

mitogen-activated protein kinase p38 binding
0.8 1E-9*mol
mw5c67812a 17f5 43cf 8acb 9bde272c1911

Proto-oncogene c-Fos
0.5 1E-9*mol
mwda4716f1 ae00 4149 aec3 12531380425a

Tyrosine-protein kinase BTK
0.0 1E-9*mol
Reactions Rate Parameters
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 => 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
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
mw3832f277_aef2_4f1d_87af_abc2a3c1a7d5 => mw13651143_feb5_49a5_adab_9105c2647446; mw3832f277_aef2_4f1d_87af_abc2a3c1a7d5 mw66285193_607e_42b6_b726_c2409a2ce563*mw3832f277_aef2_4f1d_87af_abc2a3c1a7d5/(mwa4c28075_8524_4874_aee5_c38231bfbaae+mw3832f277_aef2_4f1d_87af_abc2a3c1a7d5) mwa4c28075_8524_4874_aee5_c38231bfbaae=1.5 nanomole; mw66285193_607e_42b6_b726_c2409a2ce563=1.0 nanomole/second
mw6939cefe_e7ff_4a3f_b45b_a9234d1b5573 => mw8a358487_b18b_42df_a646_cd75eb5bfcc2; mw6939cefe_e7ff_4a3f_b45b_a9234d1b5573 mwa68f7af3_30af_4fa0_9290_9e005c875763*mw6939cefe_e7ff_4a3f_b45b_a9234d1b5573 mwa68f7af3_30af_4fa0_9290_9e005c875763=1.4 1/second
mw8a358487_b18b_42df_a646_cd75eb5bfcc2 => mwc844b7c0_98f5_4d0d_8f0c_00dfe8b54e6d; mw8a358487_b18b_42df_a646_cd75eb5bfcc2 mwbad3f510_fbca_4aa7_a4c2_5c1b47297802*mw8a358487_b18b_42df_a646_cd75eb5bfcc2^mw4d5fd70d_8603_4056_adfa_5af26d657455/(mw2fa0d3fe_4e99_49d2_a339_089198589a1e+mw8a358487_b18b_42df_a646_cd75eb5bfcc2^mw4d5fd70d_8603_4056_adfa_5af26d657455) mwbad3f510_fbca_4aa7_a4c2_5c1b47297802=2.35 nanomole/second; mw2fa0d3fe_4e99_49d2_a339_089198589a1e=0.43 nanomole; mw4d5fd70d_8603_4056_adfa_5af26d657455=1.0
mwbee11634_55df_4a3f_998a_634dfaf46fd7 => mwd9e7a9b9_6f1b_4bbc_afa5_6cb192b62ce8; mwbee11634_55df_4a3f_998a_634dfaf46fd7 mwafa60fbe_9272_468d_94e7_b82b985f938c*mwbee11634_55df_4a3f_998a_634dfaf46fd7 mwafa60fbe_9272_468d_94e7_b82b985f938c=0.61 1/second
mwd9e7a9b9_6f1b_4bbc_afa5_6cb192b62ce8 => mwfed5a135_c91b_4d20_91b2_3a61723544dd; mwd9e7a9b9_6f1b_4bbc_afa5_6cb192b62ce8 mw1a1570ff_e786_473f_860b_2e7694acfcc2*mwd9e7a9b9_6f1b_4bbc_afa5_6cb192b62ce8/(mwf88d190e_a505_4f7e_ac8d_e43997c74b9c+mwd9e7a9b9_6f1b_4bbc_afa5_6cb192b62ce8) mwf88d190e_a505_4f7e_ac8d_e43997c74b9c=0.62 nanomole; mw1a1570ff_e786_473f_860b_2e7694acfcc2=1.14 nanomole/second
mwb71eb539_dca6_47ab_8df5_430d84af0bfb => mw97345a67_a8e8_42aa_8e62_69e9d2b6cf45; mwb71eb539_dca6_47ab_8df5_430d84af0bfb mw286a7792_09c4_443e_98f4_a68f66a1f380*mwb71eb539_dca6_47ab_8df5_430d84af0bfb mw286a7792_09c4_443e_98f4_a68f66a1f380=1.0 1/second
mw97345a67_a8e8_42aa_8e62_69e9d2b6cf45 => mw5c67812a_17f5_43cf_8acb_9bde272c1911; mw97345a67_a8e8_42aa_8e62_69e9d2b6cf45 mw2a0659f9_eab8_4ada_8f82_23068b9986eb*mw97345a67_a8e8_42aa_8e62_69e9d2b6cf45/(mw13b39522_0751_4041_a78e_871cd5d81592+mw97345a67_a8e8_42aa_8e62_69e9d2b6cf45) mw13b39522_0751_4041_a78e_871cd5d81592=0.2 nanomole; mw2a0659f9_eab8_4ada_8f82_23068b9986eb=1.5 nanomole/second
mw64453fc5_a275_4bba_84f0_2af249b31514 => mwda4716f1_ae00_4149_aec3_12531380425a; mw64453fc5_a275_4bba_84f0_2af249b31514 mwb336e12c_0e62_4fff_94c0_2771b1a19065*mw64453fc5_a275_4bba_84f0_2af249b31514 mwb336e12c_0e62_4fff_94c0_2771b1a19065=0.2 1/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.