Boolean models — MAPK demo results
Generated by run_mapk_demo.py; do not edit by hand. Part of
BOOLEAN_MODELS.
1. Translation
| module | variables | signed edges | inputs (no incoming edge) | bnet |
|---|---|---|---|---|
modules/erk_cascade.yaml |
10 | 15 | adaptor_recruitment, rasgap_step |
out/erk_cascade.bnet |
modules/p38_cascade.yaml |
6 | 6 | stress_input |
out/p38_cascade.bnet |
modules/jnk_cascade.yaml |
6 | 5 | stress_input, jnk_negative_regulation |
out/jnk_cascade.bnet |
modules/jak_stat_signaling.yaml |
12 | 16 | ligand_receptor_engagement, ptp_dephosphorylation, pias_restraint, alt_stat_inputs |
out/jak_stat_signaling.bnet |
The ERK translation is also exported as SBML-qual via biodivine-aeon: out/erk_cascade.sbml.
targets, factors
adaptor_recruitment, adaptor_recruitment
ras_gef_step, adaptor_recruitment & !(erk_mapk | erk_output | sprouty_spred_feedback)
ras_active, ras_gef_step & !rasgap_step
rasgap_step, rasgap_step
raf_map3k, ras_active & !(erk_mapk | sprouty_spred_feedback)
mek_map2k, raf_map3k
erk_mapk, mek_map2k & !mapk_negative_regulation
erk_output, erk_mapk
mapk_negative_regulation, erk_output
sprouty_spred_feedback, erk_output
2. Calibration of wiring against external sources
Edges are compared on the shared symbols of the reviewed mappings (models/boolean/*/mapping_to_modules.yaml). -> activates, -| inhibits.
BBM-070
erk_cascade — 12 module edges, 8 BBM-070 edges on the 9 shared symbols: agree 8, sign conflicts 0, module-only 4, BBM-070-only 0.
| edge | status | reading |
|---|---|---|
ERK -> ERK_OUTPUT |
agree | |
ERK -| RAF |
agree | |
ERK_OUTPUT -| SOS |
agree | |
GRB2 -> SOS |
agree | |
MEK -> ERK |
agree | |
RAF -> MEK |
agree | |
RAS -> RAF |
agree | |
SOS -> RAS |
agree | |
DUSP -| ERK |
module-only | absent from BBM-070 (both ends mapped, no route; see mapping notes) |
ERK -| SOS |
module-only | BBM-070 routes it via ERK_OUTPUT (v_RSK), a route the module also wires; the module additionally asserts this direct edge |
ERK_OUTPUT -> DUSP |
module-only | BBM-070 reaches DUSP from ERK via unmapped intermediates (v_MSK -> v_CREB) |
RASGAP -| RAS |
module-only | RASGAP has no counterpart in BBM-070 (see mapping notes) |
External regulators of erk_cascade tiers not named by the module (9): v_AKT -| RAF, v_AP1 -| MEK, v_CREB -> DUSP, v_EGFR -> GRB2, v_FRS2 -> GRB2, v_PKC -> RAF, v_PLCG -> RAS, v_PPP2CA -| MEK, v_TGFBR -> GRB2
p38_cascade — 6 module edges, 3 BBM-070 edges on the 6 shared symbols: agree 2, sign conflicts 0, module-only 4, BBM-070-only 1.
| edge | status | reading |
|---|---|---|
DUSP -| P38 |
agree | |
P38 -> P38_OUTPUT |
agree | |
MKK36 -> P38 |
module-only | MKK36 has no counterpart in BBM-070 (see mapping notes) |
P38_OUTPUT -> DUSP |
module-only | BBM-070 reaches DUSP from P38 via unmapped intermediates (v_MSK -> v_CREB) |
STRESS -> STRESS_MAP3K |
module-only | STRESS has no counterpart in BBM-070 (see mapping notes) |
STRESS_MAP3K -> MKK36 |
module-only | MKK36 has no counterpart in BBM-070 (see mapping notes) |
STRESS_MAP3K -> P38 |
BBM-070-only | collapsed path (module expresses it via intermediate tiers) |
External regulators of p38_cascade tiers not named by the module (4): v_ATM -> STRESS_MAP3K, v_CREB -> DUSP, v_GADD45 -> STRESS_MAP3K, v_TGFBR -> STRESS_MAP3K
jnk_cascade — 5 module edges, 3 BBM-070 edges on the 6 shared symbols: agree 2, sign conflicts 0, module-only 3, BBM-070-only 1.
| edge | status | reading |
|---|---|---|
DUSP -| JNK |
agree | |
JNK -> JNK_OUTPUT |
agree | |
MKK47 -> JNK |
module-only | MKK47 has no counterpart in BBM-070 (see mapping notes) |
STRESS -> STRESS_MAP3K |
module-only | STRESS has no counterpart in BBM-070 (see mapping notes) |
STRESS_MAP3K -> MKK47 |
module-only | MKK47 has no counterpart in BBM-070 (see mapping notes) |
STRESS_MAP3K -> JNK |
BBM-070-only | collapsed path (module expresses it via intermediate tiers) |
External regulators of jnk_cascade tiers not named by the module (4): v_ATM -> STRESS_MAP3K, v_CREB -> DUSP, v_GADD45 -> STRESS_MAP3K, v_TGFBR -> STRESS_MAP3K
SIGNOR-EGF
erk_cascade — 12 module edges, 8 SIGNOR-EGF edges on the 9 shared symbols: agree 8, sign conflicts 0, module-only 4, SIGNOR-EGF-only 0.
| edge | status | reading |
|---|---|---|
ERK -> ERK_OUTPUT |
agree | |
ERK -| RAF |
agree | |
ERK -| SOS |
agree | |
GRB2 -> SOS |
agree | |
MEK -> ERK |
agree | |
RAF -> MEK |
agree | |
RAS -> RAF |
agree | |
SOS -> RAS |
agree | |
DUSP -| ERK |
module-only | DUSP has no counterpart in SIGNOR-EGF (see mapping notes) |
ERK_OUTPUT -> DUSP |
module-only | DUSP has no counterpart in SIGNOR-EGF (see mapping notes) |
ERK_OUTPUT -| SOS |
module-only | SIGNOR-EGF collapses this into the direct ERK - |
RASGAP -| RAS |
module-only | RASGAP has no counterpart in SIGNOR-EGF (see mapping notes) |
External regulators of erk_cascade tiers not named by the module (4): EGFR -> GRB2, PTPN11 -> RAS, SRC -> GRB2, SRC -| RAS
jnk_cascade — 4 module edges, 3 SIGNOR-EGF edges on the 5 shared symbols: agree 3, sign conflicts 0, module-only 1, SIGNOR-EGF-only 0.
| edge | status | reading |
|---|---|---|
JNK -> JNK_OUTPUT |
agree | |
MKK47 -> JNK |
agree | |
STRESS_MAP3K -> MKK47 |
agree | |
DUSP -| JNK |
module-only | DUSP has no counterpart in SIGNOR-EGF (see mapping notes) |
External regulators of jnk_cascade tiers not named by the module (2): AKT -| MKK47, PAK1 -> STRESS_MAP3K
3. Dynamics (asynchronous attractors, biodivine-aeon 1.4.2)
1/0: stable in the attractor; *: oscillates.
3a. The curated ERK module as translated (feedback loops closed)
Inputs are the stimulus (adaptor recruitment) and the GAP tier; the DUSP step is ERK-induced, so it is a variable here and fixed only in the 'constitutive DUSP' scenario.
| scenario | attractor | ras_gef_step | ras_active | raf_map3k | mek_map2k | erk_mapk | erk_output | mapk_negative_regulation | sprouty_spred_feedback |
|---|---|---|---|---|---|---|---|---|---|
| no stimulus | fixed point | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| adaptor recruited | complex attractor (188 states) | * | * | * | * | * | * | * | * |
| adaptor recruited + constitutive RasGAP | fixed point | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| adaptor recruited + constitutive DUSP | fixed point | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 0 |
3b. BBM-070 (Grieco 2013) under sustained EGFR stimulus
| scenario | attractor | v_SOS | v_RAS | v_RAF | v_MEK1_2 | v_ERK | v_RSK | v_Proliferation | v_Apoptosis | v_Growth_Arrest |
|---|---|---|---|---|---|---|---|---|---|---|
| no input | 2 fixed points (identical on the shown variables) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| EGFR stimulus | complex attractor (480,801,456,128 states) | * | * | * | * | * | * | * | * | * |
3c. Counterfactual: the ERK module with its feedback loops cut
Model file: out/erk_cascade_pre_calibration.bnet.
This is the wiring the module had before the calibration: no direct ERK feedback onto RAF or SOS, and the DUSP and Sprouty steps as uninduced free inputs. It is the module's own curated feedback_cut scenario (executable_models → erk_cascade_boolean), which removes these connections:
erk_mapk→raf_map3kerk_mapk→ras_gef_steperk_output→ras_gef_steperk_output→mapk_negative_regulationerk_output→sprouty_spred_feedback
The induced steps are held off (0), or DUSP at 1 in the constitutive-DUSP scenario.
| scenario | attractor | ras_gef_step | ras_active | raf_map3k | mek_map2k | erk_mapk | erk_output | mapk_negative_regulation | sprouty_spred_feedback |
|---|---|---|---|---|---|---|---|---|---|
| no stimulus | fixed point | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| adaptor recruited | fixed point | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 |
| adaptor recruited + constitutive RasGAP | fixed point | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| adaptor recruited + constitutive DUSP | fixed point | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 0 |