Add Models/

Author: NantiaL

arFramework3/Examples/Zeilfelder_IL6_CellSystems2024/Models/L1_model.def

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+#define BSA_LINK
+
+DESCRIPTION
+"IL6 induced STAT3 activation with SOCS3 feedback and APP transcription."
+
+PREDICTOR
+t T min time	0 200
+
+COMPARTMENTS
+cyt V pl vol.
+nuc V pl vol.
+
+STATES
+JAK1_gp130 C nmol/l conc. cyt 1 "Inactive receptor"
+pJAK1_pgp130 C nmol/l conc. cyt 1 "Total phosphorylated receptor"
+
+// cSTAT3 and nSTAT3 are subsumed in STAT3 which is the total unphosphorylated pool
+// This pool is defined w.r.t. cytoplasm.
+STAT3 C nmol/l conc. cyt 1 "Unphosphorylated STAT3"
+cpSTAT3 C nmol/l conc. cyt 1 "Active cytoplasmic STAT3"
+npSTAT3 C nmol/l conc. nuc 1 "Active nuclear STAT3"
+
+nSOCS3RNA1 C au conc. nuc 0 "SOCS3 transcriptional delay"
+nSOCS3RNA2 C au conc. nuc 0 "SOCS3 transcriptional delay"
+nSOCS3RNA3 C au conc. nuc 0 "SOCS3 transcriptional delay"
+nSOCS3RNA4 C au conc. nuc 0 "SOCS3 transcriptional delay"
+nSOCS3RNA5 C au conc. nuc 0 "SOCS3 transcriptional delay"
+SOCS3RNA C au conc. cyt 1 "Cytoplasmic SOCS3 mRNA"
+SOCS3 C nmol/l conc. cyt 1 "SOCS3 protein"
+
+INPUTS
+cycloHex C ng/ml conc. "step1(t, 0, 0, input_cyclo)" "Cycloheximid"
+ActD C ng/ml conc. "0" "Actinomycin D"
+IL6 C ng/ml conc. "step1(t, 0, 0, input_il6)" "Interleukin 6"
+
+DCF C uM conc. "step1(t,0,0,1) * input_dcf" "Diclofenac"
+APAP C mM conc. "step1(t,0,0,1) * input_apap" "Acetaminophen"
+
+REACTIONS
+#define DCF_func (DCF / 500)
+#define APAP_func (APAP / 10)
+
+ -> JAK1_gp130 CUSTOM "(1-ActD) * (1-cycloHex) * receptor_pro * ( 1 + dcf_receptor_pro * DCF_func ) * ( 1 + apap_receptor_pro * APAP_func )" "Receptor production"
+JAK1_gp130 -> CUSTOM "receptor_deg * JAK1_gp130 * ( 1 + dcf_receptor_deg * DCF_func ) * ( 1 + apap_receptor_deg * APAP_func )" "Receptor degradation"
+pJAK1_pgp130 -> CUSTOM "receptor_deg * pJAK1_pgp130 * ( 1 + dcf_receptor_deg * DCF_func ) * ( 1 + apap_receptor_deg * APAP_func )" "Phosphorylated receptor degradation"
+
+JAK1_gp130 -> pJAK1_pgp130 CUSTOM "il6_act * il6_basal * JAK1_gp130 * ( 1 + dcf_il6_basal * DCF_func ) * ( 1 + apap_il6_basal * APAP_func )" "Basal receptor phosphorylation"
+JAK1_gp130 -> pJAK1_pgp130 CUSTOM "il6_act * IL6 * JAK1_gp130 * ( 1 + dcf_il6_act * DCF_func ) * ( 1 + apap_il6_act * APAP_func )" "Receptor phosphorylation"
+
+pJAK1_pgp130 + SOCS3 -> SOCS3 CUSTOM "receptor_deg_socs3 * pJAK1_pgp130 * (SOCS3/(k_sat_SOCS3 + SOCS3)) * ( 1 + dcf_receptor_deg_socs3 * DCF_func ) * ( 1 + apap_receptor_deg_socs3 * APAP_func )" "SOCS3_Bound receptor degradation"
+
+STAT3 -> cpSTAT3 CUSTOM "stat3_act * cSTAT3 * pJAK1_pgp130 * ( 1 + dcf_stat3_act * DCF_func ) * ( 1 + apap_stat3_act * APAP_func )" "Phosphorylation STAT3" 
+cpSTAT3 -> npSTAT3 CUSTOM "pstat3_imp * cpSTAT3 * ( 1 + dcf_pstat3_imp * DCF_func ) * ( 1 + apap_pstat3_imp * APAP_func )" "Import phosphorylated STAT3" 
+npSTAT3 -> STAT3 CUSTOM "stat3_dea * npSTAT3 * ( 1 + dcf_stat3_dea * DCF_func ) * ( 1 + apap_stat3_dea * APAP_func )" "STAT3 dephosphorylation (cytoplasm)"
+
+
+0 -> nSOCS3RNA1 CUSTOM "(1-ActD) * (f_SOCS3_STAT3*(npSTAT3)^n_STAT3) * ( 1 + dcf_f_SOCS3_STAT3 * DCF_func ) * ( 1 + apap_f_SOCS3_STAT3 * APAP_func )" "SOCS3 transcription"
+nSOCS3RNA1 -> nSOCS3RNA2 CUSTOM "socs3rna_delay * nSOCS3RNA1 * ( 1 + dcf_socs3rna_delay * DCF_func ) * ( 1 + apap_socs3rna_delay * APAP_func )" "SOCS3 transcriptional delay"
+nSOCS3RNA2 -> nSOCS3RNA3 CUSTOM "socs3rna_delay * nSOCS3RNA2 * ( 1 + dcf_socs3rna_delay * DCF_func ) * ( 1 + apap_socs3rna_delay * APAP_func )" "SOCS3 transcriptional delay"
+nSOCS3RNA3 -> nSOCS3RNA4 CUSTOM "socs3rna_delay * nSOCS3RNA3 * ( 1 + dcf_socs3rna_delay * DCF_func ) * ( 1 + apap_socs3rna_delay * APAP_func )" "SOCS3 transcriptional delay"
+nSOCS3RNA4 -> nSOCS3RNA5 CUSTOM "socs3rna_delay * nSOCS3RNA4 * ( 1 + dcf_socs3rna_delay * DCF_func ) * ( 1 + apap_socs3rna_delay * APAP_func )" "SOCS3 transcriptional delay"
+nSOCS3RNA5 -> SOCS3RNA CUSTOM	"socs3rna_delay * nSOCS3RNA5 * ( 1 + dcf_socs3rna_delay * DCF_func ) * ( 1 + apap_socs3rna_delay * APAP_func )" "SOCS3 transcriptional delay"
+SOCS3RNA -> 0 CUSTOM	"socs3rna_deg * SOCS3RNA * ( 1 + dcf_socs3rna_deg * DCF_func ) * ( 1 + apap_socs3rna_deg * APAP_func )" "SOCS3 mRNA degradation"
+
+#define SOCS3SAT ( socs3_sat * ( 1 + dcf_socs3_sat * DCF_func ) * ( 1 + apap_socs3_sat * APAP_func ) )
+ -> SOCS3 CUSTOM "(1-cycloHex) * socs3_pro * ( SOCS3RNA / ( SOCS3SAT + SOCS3RNA ) ) * ( 1 + dcf_socs3_pro * DCF_func ) * ( 1 + apap_socs3_pro * APAP_func )" "SOCS3 translation"
+SOCS3 -> 0 CUSTOM	"socs3_deg * SOCS3 * ( 1 + dcf_socs3_deg * DCF_func ) * ( 1 + apap_socs3_deg * APAP_func )" "SOCS3 degradation"
+
+DERIVED
+cSTAT3 C nmol/l conc. "STAT3 * ( 1 / ( (K_transport * (1 + dcf_K_transport * DCF_func) * (1 + apap_K_transport * APAP_func)) + 1 ) )"
+nSTAT3 C nmol/l conc. "(vol_cyt / vol_nuc) * ( STAT3 - cSTAT3 )"
+
+tcpSTAT3 C nmol/l conc. "cpSTAT3"
+tnpSTAT3 C nmol/l conc. "npSTAT3"
+ctSTAT3 C nmol/l conc. "cSTAT3 + cpSTAT3"
+ntSTAT3 C nmol/l conc. "nSTAT3 + npSTAT3"
+tSTAT3 C nmol/l conc. "(vol_cyt * (cSTAT3 + cpSTAT3) + vol_nuc * (nSTAT3 + npSTAT3) )/(vol_cyt+vol_nuc)"
+tpSTAT3 C nmol/l conc. "(vol_cyt * cpSTAT3 + vol_nuc * npSTAT3 )/(vol_cyt+vol_nuc)"
+tSOCS3 C nmol/l conc. "SOCS3"
+tgp130 C nmol/l conc. "JAK1_gp130 + pJAK1_pgp130"
+
+OBSERVABLES
+#ifdef BSA_LINK
+ mcyto_obs C ug/uL conc. 0 0 "mcyto"
+ mnuc_obs C ug/uL conc. 0 0 "mnuc"
+#endif
+
+binding_sites C - conc. 0 0 "scale_gp130_deg * JAK1_gp130" "Percentage IL6 binding sites"
+gp130_abs C zmol/cell conc. 0 0 "tgp130*(vol_cyt+vol_nuc)" "gp130 total"
+socs3_abs C zmol/cell conc. 0 0 "tSOCS3*vol_cyt" "SOCS3 total"
+stat3_abs C zmol/cell conc. 0 0 "tSTAT3*(vol_cyt+vol_nuc)" "total STAT3"
+SOCS3_qpcr C au conc. 0 1 "scale_socs3_qpcr_nExpID * SOCS3RNA" "SOCS3 qPCR"
+
+pY_STAT3 C - conc. 0 0 "tpSTAT3 / tSTAT3" "Phosphorylation degree"
+
+// Offsets were all reduced out
+ctSTAT3_wb_scaled C au conc. 0	0 "scale_tstat3_filename_nExpID * vol_cyt * ctSTAT3" "Total cytoplasmic STAT3"
+ntSTAT3_wb_scaled C au conc. 0	0 "scale_tstat3_filename_nExpID * (mcyto/mnuc) * vol_nuc * ntSTAT3" "Total nuclear STAT3"
+tSTAT3_wb_scaled C au conc. 0	0 "scale_tstat3_filename_nExpID * ( vol_cyt + vol_nuc ) * ( mcyto / ( mnuc + mcyto ) ) * tSTAT3" "Total STAT3"
+
+cpSTAT3_wb_scaled C au conc. 0	0 "scale_pstat3_filename_nExpID * vol_cyt * tcpSTAT3" "Cytoplasmic pSTAT3"
+npSTAT3_wb_scaled C au conc. 0	0 "scale_pstat3_filename_nExpID * (mcyto/mnuc) * vol_nuc * tnpSTAT3" "Nuclear pSTAT3"
+tpSTAT3_wb_scaled C au conc. 0	0 "scale_pstat3_filename_nExpID * ( vol_cyt + vol_nuc ) * ( mcyto / ( mnuc + mcyto ) ) * tpSTAT3" "Total pSTAT3"
+ 
+SOCS3_qpcr_scaled C au conc. 0	1 "scale_socs3_qpcr_filename_nExpID * SOCS3RNA" "SOCS3 qPCR"
+cSOCS3_wb C au conc. 0	0 "scale_csocs3_filename_nExpID * tSOCS3" "Total SOCS3"
+
+ERRORS
+#ifdef BSA_LINK
+ mcyto_obs	"sd_mcyto"
+ mnuc_obs "sd_mnuc" 
+#endif
+
+gp130_abs "sd_gp130_abs"
+socs3_abs "sd_socs3_abs"
+stat3_abs "sd_stat3_abs"
+SOCS3_qpcr "sd_socs3_qpcr"
+
+pY_STAT3 "1"
+binding_sites "1"
+
+ctSTAT3_wb_scaled "scale_tstat3_filename_nExpID * sqrt( sd_ctSTAT3^2 + sd_rel_ctSTAT3^2 * ctSTAT3^2 )"
+ntSTAT3_wb_scaled "scale_tstat3_filename_nExpID * sqrt( sd_ntSTAT3^2 + sd_rel_ntSTAT3^2 * ntSTAT3^2 )"
+tSTAT3_wb_scaled "scale_tstat3_filename_nExpID * sqrt( sd_tSTAT3^2 + sd_rel_tSTAT3^2 * tSTAT3^2 )"
+
+cpSTAT3_wb_scaled "scale_pstat3_filename_nExpID * sqrt( sd_cpSTAT3^2 + sd_rel_cpSTAT3^2 * tcpSTAT3^2 )"
+npSTAT3_wb_scaled "scale_pstat3_filename_nExpID * sqrt( sd_npSTAT3^2 + sd_rel_npSTAT3^2 * tnpSTAT3^2 )"
+tpSTAT3_wb_scaled "scale_pstat3_filename_nExpID * sqrt( sd_tpSTAT3^2 + sd_rel_tpSTAT3^2 * tpSTAT3^2 )"
+
+cSOCS3_wb "scale_csocs3_filename_nExpID * sqrt( sd_cSOCS3^2 + sd_rel_cSOCS3^2 * cSOCS3_wb^2 )"
+SOCS3_qpcr_scaled "sd_socs3_qpcr"
+
+SUBSTITUTIONS
+vcyt "0.6375"
+vnuc "0.2125"
+
+total_STAT3 "1e3 * STAT3_total"
+
+CONDITIONS
+vol_cyt "vcyt" // ((0.001*606.82)/(12.67+0.5))*12.67
+vol_nuc "vnuc"
+
+input_dcf "0"
+input_apap "0"
+
+// No initial parameters for unconserved moieities
+init_SOCS3RNA "1"
+init_nSOCS3RNA1 "1"
+init_nSOCS3RNA2 "1"
+init_nSOCS3RNA3 "1"
+init_nSOCS3RNA4 "1"
+init_nSOCS3RNA5 "1"
+init_SOCS3 "1"
+
+// Default inputs
+input_bmp2 "0"
+input_il6 "10"
+input_cyclo "0"
+input_level "0"
+
+// Totals for the conserved pools
+init_STAT3 ".5 * total_STAT3 * (vnuc+vcyt) / vcyt" // <= Defined w.r.t. cytoplasm
+init_cpSTAT3 "0"
+init_npSTAT3 ".5 * total_STAT3 * (vnuc+vcyt) / vnuc" // <= This one may not be zero because of power function in transcription model.
+
+receptor_pro "receptor_pro"
+init_JAK1_gp130 "receptor_pro * receptor_deg"
+init_pJAK1_pgp130 "0"
+
+stat3_act "stat3_act / receptor_pro"
+
+is_bmp2 "0"
+input_level "0"
+
+RANDOM
+nExpID INDEPENDENT