Rosacea Innate-Immune Axis Boolean Model

models/rosacea_innate_boolean/

A synchronous Boolean network of the cutaneous innate-immune arm of rosacea: barrier impairment and Demodex proliferation through pro-cathelicidin transcription, TLR2, KLK5/KLK7 and LL-37 to the inflammasome, mast-cell, Th1/Th17 and angiogenic branches, and on to the vascular and papulopustular phenotypes. Authored in this repository rather than curated from a publication, because no Boolean, logical or other dynamical model of rosacea has been published; PubMed returns nothing for rosacea combined with Boolean network, logical model, agent-based or mathematical model, and the computational rosacea literature is entirely network pharmacology and molecular docking. Every node maps to a pathophysiology, environmental, treatment or phenotype node in this entry, and every rule transcribes causal edges curated here, so the model asserts no biology of its own: it makes the curated chain executable, so that what the chain implies can be derived instead of argued. Nothing in it is fitted to data.

Authored in this repository synchronous Boolean network Not fitted to data
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Where this model is curated

The entry card says what the model is for: which mechanism nodes it links to, how faithfully, and what it found. This page holds the model itself.

Committed scenarios

From models/rosacea_innate_boolean/results.json. Each scenario holds its listed inputs on and every other input off, then reports the attractor the network settles into.

ScenarioActive inputsAttractorActive phenotypes
healthy
Healthy skin (no active input)
 — fixed point none
papulopustular
Papulopustular rosacea (mites, barrier impairment, fibroblast expansion)
 Barrier_intrinsic, Demodex, Fibroblast_expansion fixed point FlushingPapulesPersistent erythemaPustulesTelangiectasia
erythematotelangiectatic
Erythematotelangiectatic rosacea (neurovascular and lipid-metabolic, no mites)
 ACSL5_lipid, Barrier_intrinsic, TRP_neuropeptide fixed point FlushingPapulesPersistent erythemaPustules
uv_triggered
UV-triggered flare on a mite-colonised face
 Demodex, Fibroblast_expansion, UVB_exposure fixed point FlushingPapulesPersistent erythemaPustulesTelangiectasia
steroid_induced
Topical-corticosteroid-aggravated disease
 Corticosteroid_exposure, Demodex fixed point FlushingPapulesPersistent erythemaPustulesTelangiectasia

Intervention scan

Interventions applied singly and in combination to the papulopustular scenario. Baseline phenotypes: Flushing, Papules, Persistent erythema, Pustules, Telangiectasia.

InterventionsClearedPersisting
Acaricide Telangiectasia Flushing, Papules, Persistent erythema, Pustules
Acaricide + Brimonidine Flushing, Persistent erythema, Telangiectasia Papules, Pustules
Acaricide + Brimonidine + NLRP3 inhibitor Flushing, Persistent erythema, Telangiectasia Papules, Pustules
Acaricide + NLRP3 inhibitor Telangiectasia Flushing, Papules, Persistent erythema, Pustules
Brimonidine Flushing Papules, Persistent erythema, Pustules, Telangiectasia
Brimonidine + NLRP3 inhibitor Flushing Papules, Persistent erythema, Pustules, Telangiectasia
NLRP3 inhibitor — Flushing, Papules, Persistent erythema, Pustules, Telangiectasia
— Flushing, Papules, Persistent erythema, Pustules, Telangiectasia

Rules and where each comes from

Each rule transcribes a node or causal edge curated on Rosacea. A rule no curated edge states is marked as a background assumption.

Inputs

UVB_exposure
Ultraviolet B exposure, curated as EXACERBATES on skin barrier dysfunction.
Maps to environmental#Ultraviolet B radiation
Corticosteroid_exposure
Topical corticosteroid exposure, curated as EXACERBATES on skin barrier dysfunction.
Maps to environmental#Corticosteroid treatment
Barrier_intrinsic
Barrier impairment not attributable to the two curated exposures. Present so that barrier dysfunction is not forced to be exposure-dependent, which the entry does not claim.
Maps to pathophysiology#Skin barrier dysfunction
Demodex
Mite proliferation. An input because the entry curates no upstream cause for it.
Maps to pathophysiology#Demodex Folliculorum Proliferation
TRP_neuropeptide
TRP-channel and neuropeptide signaling. An input because its curated upstream (heat, alcohol, capsaicin triggers) is not modeled in this entry.
Maps to pathophysiology#TRP and neuropeptide signaling
Fibroblast_expansion
Expansion of the PTGDS-associated pro-inflammatory fibroblast population. An input: no upstream cause is curated.
Maps to pathophysiology#Pro-inflammatory Fibroblast Expansion
ACSL5_lipid
Lipid-metabolic reprogramming in erythematotelangiectatic disease. An input; the node itself is PROVISIONAL.
Maps to pathophysiology#ACSL5-Mediated Lipid Metabolism Dysregulation

Interventions

Acaricide
inhibits Demodex
Provenance:
  • curated_edge
Decision. treatments#Papulopustular-directed pharmacotherapy carries a curated target_mechanisms link, treatment_effect INHIBITS, onto the Demodex node.
NLRP3_inhibitor
inhibits NLRP3
Provenance:
  • cited_evidence
Decision. Not a curated treatment in the entry. Grounded in PMID:33745908, cited on the NLRP3 node, which reports that LL-37-induced rosacea-like inflammation is abrogated in Nlrp3-deficient mice and reduced by the NLRP3 inhibitor MCC950.
Brimonidine
inhibits Neurovascular_vasodilation
Provenance:
  • treatment_described
Decision. treatments#Topical brimonidine therapy is curated as reducing visible vasodilatory erythema, but carries no target_mechanisms edge, so the node it acts on is inferred from the treatment description.

Rules

Skin_barrier_dysfunction
Barrier_intrinsic or UVB_exposure or Corticosteroid_exposure
Maps to pathophysiology#Skin barrier dysfunction
Provenance:
  • environmental#Ultraviolet B radiation -EXACERBATES-> Skin barrier dysfunction
  • environmental#Corticosteroid treatment -EXACERBATES-> Skin barrier dysfunction
Decision. OR, because either exposure is described as sufficient to worsen the barrier and neither is described as necessary.
Pro_cathelicidin_transcription
Skin_barrier_dysfunction
Maps to pathophysiology#Pro-cathelicidin transcription
Provenance:
  • Skin barrier dysfunction -> Pro-cathelicidin transcription (DIRECT)
TLR2_upregulation
Demodex
Maps to pathophysiology#TLR2 upregulation
Provenance:
  • Demodex Folliculorum Proliferation -> TLR2 upregulation (INDIRECT_KNOWN_INTERMEDIATES)
Decision. Demodex is the only curated upstream of TLR2 in this entry, so in the model TLR2 cannot rise without mites. That is a property of the curated graph, not of the disease, and it is the main reason acaricide monotherapy looks more complete here than it is clinically.
KLK5_KLK7_activation
TLR2_upregulation
Maps to pathophysiology#KLK5/KLK7 activation
Provenance:
  • TLR2 upregulation -> KLK5/KLK7 activation (DIRECT)
LL37_generation
Pro_cathelicidin_transcription and KLK5_KLK7_activation
Maps to pathophysiology#LL-37 generation
Provenance:
  • Pro-cathelicidin transcription -> LL-37 generation (INDIRECT_KNOWN_INTERMEDIATES)
  • KLK5/KLK7 activation -> LL-37 generation (DIRECT)
Decision. AND, not OR. LL-37 is a proteolytic product, so it needs both the substrate arm and the protease arm; the two curated edges are conjunctive in the biology even though the edge list does not say so.
NLRP3
LL37_generation and not NLRP3_inhibitor
Maps to pathophysiology#NLRP3 Inflammasome Activation
Provenance:
  • LL-37 generation -> NLRP3 Inflammasome Activation (DIRECT)
Mast_cell_amplification
LL37_generation
Maps to pathophysiology#Mast cell-mediated amplification
Provenance:
  • LL-37 generation -> Mast cell-mediated amplification (DIRECT)
Angiogenic_remodeling
LL37_generation
Maps to pathophysiology#Angiogenic vascular remodeling
Provenance:
  • LL-37 generation -> Angiogenic vascular remodeling (DIRECT)
Th1_Th17
LL37_generation
Maps to pathophysiology#Th1/Th17 adaptive inflammation
Provenance:
  • LL-37 generation -> Th1/Th17 adaptive inflammation (INDIRECT_KNOWN_INTERMEDIATES)
STAT3_signaling
Skin_barrier_dysfunction
Maps to pathophysiology#STAT3-mediated cytokine signaling
Provenance:
  • Skin barrier dysfunction -> STAT3-mediated cytokine signaling (DIRECT)
Immune_cell_infiltration
STAT3_signaling or ACSL5_lipid or Fibroblast_expansion
Maps to pathophysiology#Immune cell infiltration
Provenance:
  • STAT3-mediated cytokine signaling -> Immune cell infiltration (DIRECT)
  • ACSL5-Mediated Lipid Metabolism Dysregulation -> Immune cell infiltration (INDIRECT_KNOWN_INTERMEDIATES)
  • Pro-inflammatory Fibroblast Expansion -> Immune cell infiltration (INDIRECT_KNOWN_INTERMEDIATES)
Decision. OR; the three curated edges are independent contributors.
Papulopustular_inflammation
NLRP3 or Immune_cell_infiltration or Th1_Th17
Maps to pathophysiology#Papulopustular inflammation
Provenance:
  • NLRP3 Inflammasome Activation -> Papulopustular inflammation (INDIRECT_KNOWN_INTERMEDIATES)
  • Immune cell infiltration -> Papulopustular inflammation (DIRECT)
  • Th1/Th17 adaptive inflammation -> Papulopustular inflammation (DIRECT)
Decision. OR, the literal reading of three separately curated edges. This is the model's least safe assumption: if lesion formation in fact requires several arms together, OR understates how much therapy is needed, and the single-agent results below would be optimistic.
Neurovascular_vasodilation
(Mast_cell_amplification or Fibroblast_expansion or TRP_neuropeptide) and not Brimonidine
Maps to pathophysiology#Neurovascular vasodilation
Provenance:
  • Mast cell-mediated amplification -> Neurovascular vasodilation (DIRECT)
  • Pro-inflammatory Fibroblast Expansion -> Neurovascular vasodilation (DIRECT)
  • TRP and neuropeptide signaling -> Neurovascular vasodilation (DIRECT)

Outputs

Flushing
Neurovascular_vasodilation
Maps to phenotypes#Flushing
Provenance:
  • Neurovascular vasodilation -> Flushing (DIRECT)
Persistent_erythema
Neurovascular_vasodilation or Angiogenic_remodeling
Maps to phenotypes#Persistent centrofacial erythema
Provenance:
  • Neurovascular vasodilation -> Persistent centrofacial erythema (INDIRECT_KNOWN_INTERMEDIATES)
  • Angiogenic vascular remodeling -> Persistent centrofacial erythema (INDIRECT_KNOWN_INTERMEDIATES)
Telangiectasia
Angiogenic_remodeling
Maps to phenotypes#Facial telangiectasia
Provenance:
  • Angiogenic vascular remodeling -> Facial telangiectasia (DIRECT)
Papules
Papulopustular_inflammation
Maps to phenotypes#Papules
Provenance:
  • Papulopustular inflammation -> Papules (DIRECT)
Pustules
Papulopustular_inflammation
Maps to phenotypes#Pustules
Provenance:
  • Papulopustular inflammation -> Pustules (DIRECT)

Run it locally

uv run python models/rosacea_innate_boolean/run.py --printuv run python models/rosacea_innate_boolean/run.py --checkuv run python models/rosacea_innate_boolean/run.py

Files

results.jsonrun.pyspec.yaml

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