Boolean
derived from module
The module's connections read as a signed regulatory graph and translated by ai-gene-review module-to-bnet. Each negative regulator is wired where the module says it acts: SOCS and the phosphatases on JAK, the phosphatases and PIAS on nuclear STATs. STAT transcription carries activation_logic because ERK serine phosphorylation of STATs only tunes maximal transcription, so it is declared an omitted regulator. In every scenario the phosphatase, PIAS and JAK-independent STAT inputs are held off unless stated.
6 scenario(s): all expectations hold No cytokine · Sustained cytokine · SOCS knocked out · JAK inhibited · PIAS active · JAK-independent STAT input
Run in browser →
Boolean
derived from module
The module's connections read as a signed regulatory graph, translated by ai-gene-review module-to-bnet with the default rule (active when any activator is active and no inhibitor is). Every rule comes from the module's connections; nothing is edited in the network itself. The scenarios are checked by exhaustive asynchronous attractor enumeration in validation, so a change to the wiring that alters any of these behaviours fails loudly.
6 scenario(s): all expectations hold No stimulus · Sustained stimulus · Feedback loops cut · DUSP and Sprouty knocked out · MEK inhibited · RasGAP active
Run in browser →
Boolean
external
MAPK network and cancer cell fate decisions (Grieco 2013)
Published logical model of the MAPK network (BBM-070 in the Biodivine Boolean Models corpus). Used as a calibration source for this module's wiring through a reviewed id-mapping; its ERK ⊣ RAF and RSK ⊣ SOS feedbacks prompted the feedback connections curated into this module. Under growth-factor input it has a cyclic attractor, as the derived model does in its sustained-stimulus scenario, but the agreement is in attractor kind only: BBM-070 attributes its transience to receptor-level feedback (receptor degradation and PKC), which this module does not include, and reports that its downstream feedbacks do not qualitatively change the outcome.
Agent-based
derived from module
Simulates 100 discrete receptor-ligand / GalNAc-conjugate agents traversing the seven stages of hepatocyte ASGR-mediated uptake under uniform uncalibrated default transition rates (base_rate = 0.45, competing_inhibitor_factor = 0.25). Under wild-type baseline conditions, active RAB7A/ESCRT late endosomal maturation (escrt_rab7_late_endosome) attenuates the cytosolic escape transition from acidified sorting endosomes, yielding ~47% receptor recycling (ehd1_receptor_recycling), ~43% lysosomal routing/degradation (ctsd_lysosomal_degradation), and ~10% productive cytosolic escape (cytosolic_galnac_escape). Note that these percentages arise from uniform uncalibrated ABM transition kinetics rather than calibrated clinical pharmacokinetics (where only a minuscule portion of endocytosed GalNAc-ASO/siRNA escapes into the cytosol in vivo; PMID:29069408), and the RAB7A-depletion escape enhancement (10% -> 47%) is a qualitative cross-modality extrapolation from hepatic LNP endosomal escape competition (PMID:41814093). Perturbing individual stages reproduces the qualitative directionality of ASGR/clathrin uptake blockade, V-ATPase inhibition, EHD1 recycling loss, and RAB7A depletion.
6 scenario(s): all expectations hold Wild-type hepatocyte GalNAc uptake (rapid receptor recycling + lysosomal sequestration dominate; ~10% cytosolic escape) · RAB7A / late-endosomal maturation loss (blocks lysosomal delivery and increases cytosolic GalNAc payload escape) · Clathrin / AP-2 / DNM2 internalization block (GalNAc conjugates trapped on sinusoidal ASGR1/ASGR2) · V-ATPase acidification block (ATP6V1A loss / bafilomycin A1; arrest in neutral nascent vesicles) · EHD1 recycling block (diverts sorting-endosome flux into lysosomal degradation and cytosolic escape) · CTSD lysosomal proteolysis block (undegraded cargo accumulates in late endosomes/lysosomes)
Run in browser →
Agent-based
derived from module
Simulates 100 discrete cargo/nanoparticle agents traversing the seven stages of the module under uniform uncalibrated default transition rates (base_rate = 0.45, competing_inhibitor_factor = 0.25). In wild-type baseline trafficking, active RAB7A/ESCRT late endosomal maturation (escrt_rab7_late_endosome) attenuates the cytosolic escape transition from acidified early endosomes, resulting in ~47% recycling (ehd1_recycling_branch), ~43% lysosomal degradation (ctsd_lysosomal_degradation), and ~10% cytosolic escape (cytosolic_cargo_escape) — reproducing the qualitative hierarchy observed by LysoTag barcoding (~8% baseline cytosolic LNP escape in vivo; PMID:41814093). Perturbing individual stages reproduces the qualitative direction of genetic and pharmacological blocks across the pathway.
6 scenario(s): all expectations hold Wild-type baseline trafficking (recycling + lysosomal degradation dominate; ~10% cytosolic escape) · RAB7A / late-endosomal maturation loss (diverts flux from lysosomes and increases cytosolic escape) · Clathrin / AP-2 endocytosis block (cargo trapped at the cell surface) · V-ATPase acidification block (bafilomycin A1 / ATP6V1A loss; arrest in nascent endocytic vesicles) · EHD1 recycling block (diverts sorting-endosome cargo toward lysosomal degradation and escape) · CTSD lysosomal proteolysis block (undegraded cargo accumulates in late endosomes/lysosomes)
Run in browser →
Agent-based
derived from module
Tracks a cohort of 100 extracellular apoB-100 LDL particles (apob_ligand) through LDLR-mediated clathrin endocytosis (ldlr_endocytosis) and lysosomal acid lipase cholesteryl-ester hydrolysis (lipa_ce_hydrolysis), gated by secreted PCSK9 chaperone activity (pcsk9_degradation).
4 scenario(s): all expectations hold Maximal PCSK9-independent hepatic LDL clearance (complete lysosomal cholesteryl-ester hydrolysis) · PCSK9 gain-of-function / familial hypercholesterolaemia (LDLR degraded; extracellular LDL retention) · LDLR loss-of-function familial hypercholesterolaemia (receptor uptake blocked) · LIPA loss-of-function (Wolman disease / CESD; endolysosomal cholesteryl-ester accumulation)
Run in browser →
Kinetic
external
Maud kinetic model of the methionine cycle (biosustain)
Bayesian kinetic model of the methionine cycle from the biosustain Maud project. Only its regulation tables (allostery, competitive inhibition) are ingested, as evidence for this module's regulatory connections through a reviewed id-mapping; stoichiometry, kinetics and priors are not used. Compare with ai-gene-review compare-module-regulation.
Evidence: file:models/methionine/README.md
Agent-based
derived from module
Simulates 100 discrete IgG/albumin cargo agents traversing the seven stages of endothelial and epithelial FcRn trafficking under uniform uncalibrated default transition rates (base_rate = 0.45, competing_inhibitor_factor = 0.25). Under wild-type baseline conditions, active FcRn acidic capture (fcrn_ph_dependent_salvage) attenuates late-endosomal routing (rab7_late_endosome_routing) from acidified sorting endosomes, rescuing 80% of internalized IgG/albumin via EHD1/SNAP23 exocytic recycling (ehd1_snap23_salvage_exocytosis) while only 20% undergoes lysosomal catabolism (ctsd_lysosomal_catabolism). Inactivating FcRn salvage (modeling FCGRT/B2M deficiency or therapeutic anti-FcRn blockade such as efgartigimod) diverts 100% of internalized cargo into RAB7A/CTSD lysosomal catabolism.
6 scenario(s): all expectations hold Wild-type FcRn salvage dominance (80% exocytic salvage/transcytosis vs. 20% lysosomal catabolism) · FcRn / B2M deficiency or anti-FcRn blockade (efgartigimod; 100% diversion to lysosomal catabolism) · V-ATPase acidification block (ATP6V1A loss / bafilomycin A1; failure of acidic histidine protonation switch) · EHD1 / SNAP23 recycling & exocytosis block (FcRn-bound cargo trapped in recycling/sorting endosomes) · RAB7A late-endosomal maturation block (eliminates lysosomal catabolism and routes 100% of cargo to FcRn salvage) · Clathrin / DNM2 endocytic uptake block (albumin and IgG retained in extracellular plasma pool)
Run in browser →
Agent-based
derived from module
Simulates 100 discrete SORL1/sorting-receptor cargo agents traversing the seven stages of endocytic internalization and retrograde endosome-to-TGN retrieval under uniform uncalibrated default transition rates (base_rate = 0.45, competing_inhibitor_factor = 0.25). Under wild-type baseline conditions, active retromer recruitment (retromer_csc_cargo_selection) attenuates ESCRT/RAB7A degradative progression (escrt_rab7_degradative_routing), retrieving 80% of internalized receptor-cargo complexes to the trans-Golgi network (rab9a_ap1_tgn_delivery) while only 20% undergoes lysosomal proteolysis (ctsd_lysosomal_proteolysis). Inactivating the retromer complex (modeling VPS35/VPS26A/VPS29 deficiency) abolishes TGN retrieval and diverts 100% of internalized receptors into RAB7A/CTSD lysosomal degradation — while simultaneous RAB7A inhibition rescues cargo from lysosomal proteolysis, reproducing the genetic suppression of retromer loss by Rab7 reduction (PMID:32286230).
6 scenario(s): all expectations hold Wild-type retromer retrograde sorting (80% TGN retrieval vs. 20% lysosomal proteolysis) · Retromer loss-of-function (VPS35 / VPS26A / VPS29 deficiency; 100% misrouting to lysosomal degradation) · RAB9A / AP-1 TGN docking block (retrograde carriers arrested prior to trans-Golgi network delivery) · RAB7A late-endosomal maturation block (suppresses lysosomal degradation and routes 100% of cargo to TGN retrieval) · V-ATPase acidification block (ATP6V1A loss; arrest in nascent endocytic vesicles) · Clathrin / AP-2 / DNM2 internalization block (SORL1-cargo complexes trapped at the cell surface)
Run in browser →
Boolean
derived from module
The module's connections read as a signed regulatory graph and translated by ai-gene-review module-to-bnet with the default rule (active when any activator is active and no inhibitor is). Its one loop is p38 output inducing the MKP-1/DUSP1 phosphatase that dephosphorylates p38.
4 scenario(s): all expectations hold No stress · Sustained stress · MKP-1 lost · MKK3/6 inhibited
Run in browser →