Merge pull request #10 from akutuva21/master

Migrating to ruleworld

Author: jrfaeder

.github/workflows/validate.yml

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+name: Validate RuleHub Metadata
+
+on:
+  pull_request:
+  push:
+    branches:
+      - master
+      - main
+
+jobs:
+  validate:
+    runs-on: ubuntu-latest
+
+    steps:
+      - name: Checkout
+        uses: actions/checkout@v4
+
+      - name: Setup Node
+        uses: actions/setup-node@v4
+        with:
+          node-version: '20'
+
+      - name: Validate metadata
+        run: node scripts/validate-metadata.js
+
+      - name: Regenerate manifest
+        run: node scripts/generate-manifest.js --root . --output manifest.generated.json
+
+      - name: Check manifest is up to date
+        run: diff -u manifest.json manifest.generated.json

AddingModels.md

@@ -4,9 +4,12 @@
 2. Name is determined by either first author or the contributor, followed by the year of publication or contribution. If there is already a model in either section with that name, add another descriptive keyword (must start with a letter not a number) to the name, e.g., Blinov2006EGFR.
 3. Make a directory with the name of the model in the corresponding section.
 4. Put all model files and (optionally) associated scripts in this directory.
-5. Create a README.md file in the directory based on the template provided in the corresponding model section (Published or Contributed).
-6. If there are multiple model files/scripts, provide a table in the README.md file that gives a brief description of each. 
-7. (optional) Provide additional annotation in each model file based on the annotation keywords provided in ...
+5. Create a metadata.yaml file in the directory following the field names documented in metadata-schema.yaml.
+6. Create a README.md file in the directory based on the template provided in the corresponding model section (Published or Contributed).
+7. If there are multiple model files/scripts, provide a table in the README.md file that gives a brief description of each.
+8. If there are multiple BNGL model files in a single directory, include a collection section in metadata.yaml describing the variant type and count.
+9. Run node scripts/validate-metadata.js and node scripts/generate-manifest.js --root . --output manifest.json before opening a pull request.
+10. (optional) Provide additional annotation in each model file based on the annotation keywords provided in ...
 
 ## Guidelines for journal articles linking to RuleHub
 

Contributed/BNGPlayground_Examples/biology/aktsignaling/README.md

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+# akt signaling
+
+Signaling rates
+
+## Provenance
+
+This BNGL example was generated in BNG Playground and curated by Achyudhan.
+No external literature citation is associated with this model unless one is added manually.
+
+## Compatibility
+
+- BNG2 compatible: yes
+- Simulation methods: ode
+- Imported from: ai-generated
+
+## Files
+
+- akt-signaling.bngl
+
+## Tags
+
+akt, signaling, growthfactor, rtk, pi3k, mtorc2, mtorc1, s6k

Contributed/BNGPlayground_Examples/biology/aktsignaling/akt-signaling.bngl

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+begin model
+begin parameters
+    # Signaling rates
+    k_bind 1e-3        # RTK-GF binding
+    k_unbind 1e-4      # GF dissociation
+    k_rtk_act 0.5      # Autophosphorylation
+    k_pi3k 0.2         # PI3K recruitment/activation
+    k_akt_t308 0.5     # PDK1-mediated T308 phos
+    k_akt_s473 0.3     # mTORC2-mediated S473 phos
+    k_mtorc1 0.4       # Akt-mediated mTORC1 activation
+    k_s6k_act 0.2      # mTORC1-mediated S6K phos
+    
+    # Negative feedback / resetting
+    k_reset 0.1        # General phosphatase/deactivation
+    k_fb 0.05          # S6K-mediated inhibition of RTK signaling
+    
+    # Total concentrations
+    GF_tot 100
+    RTK_tot 50
+    PI3K_tot 40
+    AKT_tot 100
+    mTORC2_tot 20
+    mTORC1_tot 50
+    S6K_tot 30
+end parameters
+
+begin molecule types
+    GrowthFactor(r)
+    RTK(l,state~U~P,fb_site~open~closed)
+    PI3K(state~off~on)
+    # Akt has two critical phosphorylation sites
+    AKT(t308~U~P,s473~U~P)
+    mTORC2(state~on)
+    mTORC1(state~off~on)
+    S6K(state~U~P)
+end molecule types
+
+begin seed species
+    GrowthFactor(r) GF_tot
+    RTK(l,state~U,fb_site~open) RTK_tot
+    PI3K(state~off) PI3K_tot
+    AKT(t308~U,s473~U) AKT_tot
+    mTORC2(state~on) mTORC2_tot
+    mTORC1(state~off) mTORC1_tot
+    S6K(state~U) S6K_tot
+end seed species
+
+begin observables
+    # KEY BIOLOGICAL OUTPUTS
+    Molecules Active_RTK    RTK(state~P)              # Receptor tyrosine kinase activation
+    Molecules Active_PI3K   PI3K(state~on)           # PI3K recruitment to membrane
+    Molecules pAkt_T308     AKT(t308~P)              # PDK1-mediated phosphorylation
+    Molecules pAkt_S473     AKT(s473~P)              # mTORC2-mediated phosphorylation
+    Molecules Double_pAkt   AKT(t308~P,s473~P)       # Fully active Akt
+    Molecules Active_mTORC1 mTORC1(state~on)         # Downstream growth effector
+end observables
+
+begin reaction rules
+    ## RECEPTOR ACTIVATION & FEEDBACK
+    # Growth factor binds to open RTK
+    GrowthFactor(r) + RTK(l,fb_site~open) <-> GrowthFactor(r!1).RTK(l!1,fb_site~open) k_bind,k_unbind
+    
+    # Ligand-bound RTK becomes active
+    GrowthFactor(r!1).RTK(l!1,state~U) -> GrowthFactor(r!1).RTK(l!1,state~P) k_rtk_act
+    
+    ## PI3K / AKT PATHWAY
+    # Active RTK recruits and activates PI3K
+    RTK(state~P) + PI3K(state~off) -> RTK(state~P) + PI3K(state~on) k_pi3k
+    
+    # Active PI3K facilitates Akt phosphorylation at T308 (PDK1 proxy)
+    PI3K(state~on) + AKT(t308~U) -> PI3K(state~on) + AKT(t308~P) k_akt_t308
+    
+    # Constitutive mTORC2 phosphorylates Akt at S473
+    mTORC2() + AKT(s473~U) -> mTORC2() + AKT(s473~P) k_akt_s473
+    
+    ## MTOR SIGNALING & FEEDBACK
+    # Double-phosphorylated Akt activates mTORC1
+    AKT(t308~P,s473~P) + mTORC1(state~off) -> AKT(t308~P,s473~P) + mTORC1(state~on) k_mtorc1
+    
+    # mTORC1 activates S6K,which mediates feedback
+    mTORC1(state~on) + S6K(state~U) -> mTORC1(state~on) + S6K(state~P) k_s6k_act
+    
+    # Negative feedback: pS6K inhibits RTK ligand binding by "closing" the feedback site
+    S6K(state~P) + RTK(fb_site~open) -> S6K(state~P) + RTK(fb_site~closed) k_fb
+    
+    ## RESETTING MECHANISMS
+    RTK(state~P) -> RTK(state~U) k_reset
+    PI3K(state~on) -> PI3K(state~off) k_reset
+    AKT(t308~P) -> AKT(t308~U) k_reset
+    AKT(s473~P) -> AKT(s473~U) k_reset
+    mTORC1(state~on) -> mTORC1(state~off) k_reset
+    S6K(state~P) -> S6K(state~U) k_reset
+    RTK(fb_site~closed) -> RTK(fb_site~open) k_reset
+end reaction rules
+
+begin actions
+    generate_network({overwrite=>1})
+    simulate({method=>"ode",t_start=>0,t_end=>500,n_steps=>250})
+end actions
+end model

Contributed/BNGPlayground_Examples/biology/aktsignaling/metadata.yaml

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+id: "akt-signaling"
+name: "akt signaling"
+description: "Signaling rates"
+contributors:
+  - name: "Achyudhan"
+tags: ["akt", "signaling", "growthfactor", "rtk", "pi3k", "mtorc2", "mtorc1", "s6k"]
+category: "signaling"
+compatibility:
+  bng2_compatible: true
+  simulation_methods: ["ode"]
+  uses_compartments: false
+  uses_energy: false
+  uses_functions: false
+  nfsim_compatible: false
+source:
+  origin: "ai-generated"
+  original_format: "bngl"
+  original_repository: "bionetgen-web-simulator"
+  source_path: "example-models/akt-signaling.bngl"
+playground:
+  visible: false
+  gallery_category: "signaling"
+  featured: false
+  difficulty: "advanced"

Contributed/BNGPlayground_Examples/biology/allostericactivation/README.md

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+# allosteric activation
+
+Binding constants
+
+## Provenance
+
+This BNGL example was generated in BNG Playground and curated by Achyudhan.
+No external literature citation is associated with this model unless one is added manually.
+
+## Compatibility
+
+- BNG2 compatible: yes
+- Simulation methods: ode
+- Imported from: ai-generated
+
+## Files
+
+- allosteric-activation.bngl
+
+## Tags
+
+allosteric, activation, enzyme, substrate, activator, product

Contributed/BNGPlayground_Examples/biology/allostericactivation/allosteric-activation.bngl

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+begin model
+begin parameters
+    # Binding constants
+    k_on_S 2e-3        # Substrate binding to enzyme
+    k_off_S 5e-4       # Substrate dissociation
+    k_on_A 1.5e-3      # Activator binding (cooperative step 1)
+    k_off_A 3e-4       # Activator dissociation
+    
+    # Catalytic rates
+    k_cat_basal 0.02   # Catalysis by inactive/partially-active enzyme
+    k_cat_full  0.25   # Catalysis by fully activated enzyme
+    
+    # Feedback
+    k_inh 0.01         # Product-mediated feedback inhibition
+end parameters
+
+begin molecule types
+    # Enzyme has a substrate site (s),two activator sites (a1,a2),and can be inhibited (i)
+    Enzyme(s,a1,a2,i~off~on)
+    Substrate(b)
+    Activator(b)
+    Product()
+end molecule types
+
+begin seed species
+    Enzyme(s,a1,a2,i~off) 50
+    Substrate(b) 500
+    Activator(b) 200
+    Product() 0
+end seed species
+
+begin observables
+    # KEY BIOLOGICAL OUTPUTS
+    Molecules Free_Enzyme     Enzyme(a1,a2,s,i~off)            # Available enzyme
+    Molecules Single_Bound    Enzyme(a1!1,a2).Activator(b!1)    # Partially activated
+    Molecules Double_Bound    Enzyme(a1!1,a2!2).Activator(b!1).Activator(b!2) # Fully activated
+    Molecules Product_Count   Product()                         # Cumulative product
+    Molecules Inhibited_Enz   Enzyme(i~on)                      # Enzyme sequestered by feedback
+end observables
+
+begin reaction rules
+    ## ALLOSTERIC COOPERATIVITY
+    # First activator binding
+    Enzyme(a1,i~off) + Activator(b) <-> Enzyme(a1!1,i~off).Activator(b!1) k_on_A,k_off_A
+    
+    # Second activator binding (cooperative recruitment)
+    Enzyme(a1!+,a2,i~off) + Activator(b) <-> Enzyme(a1!+,a2!1,i~off).Activator(b!1) k_on_A*2,k_off_A/2
+    
+    ## SUBSTRATE PROCESSING
+    # Substrate binds to enzyme (any state,but faster if active)
+    Enzyme(s,i~off) + Substrate(b) <-> Enzyme(s!1,i~off).Substrate(b!1) k_on_S,k_off_S
+    
+    # Basal catalysis (inactive or partially active)
+    Enzyme(s!1,a2,i~off).Substrate(b!1) -> Enzyme(s,a2,i~off) + Product() k_cat_basal
+    
+    # Enhanced catalysis (both allosteric sites bound)
+    Enzyme(s!1,a1!+,a2!+,i~off).Substrate(b!1) -> Enzyme(s,a1!+,a2!+,i~off) + Product() k_cat_full
+    
+    ## FEEDBACK REGULATION
+    # Product mediates negative feedback inhibition (e.g.,metabolic control)
+    Product() + Enzyme(i~off) -> Enzyme(i~on) k_inh
+    Enzyme(i~on) -> Enzyme(i~off) k_off_S
+end reaction rules
+
+begin actions
+    generate_network({overwrite=>1})
+    simulate({method=>"ode",t_end=>5000,n_steps=>300})
+end actions
+end model

Contributed/BNGPlayground_Examples/biology/allostericactivation/metadata.yaml

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+id: "allosteric-activation"
+name: "allosteric activation"
+description: "Binding constants"
+contributors:
+  - name: "Achyudhan"
+tags: ["allosteric", "activation", "enzyme", "substrate", "activator", "product"]
+category: "signaling"
+compatibility:
+  bng2_compatible: true
+  simulation_methods: ["ode"]
+  uses_compartments: false
+  uses_energy: false
+  uses_functions: false
+  nfsim_compatible: false
+source:
+  origin: "ai-generated"
+  original_format: "bngl"
+  original_repository: "bionetgen-web-simulator"
+  source_path: "example-models/allosteric-activation.bngl"
+playground:
+  visible: false
+  gallery_category: "signaling"
+  featured: false
+  difficulty: "advanced"

Contributed/BNGPlayground_Examples/biology/ampksignaling/README.md

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+# ampk signaling
+
+AMPK signaling: The cellular energy sensor.
+
+## Provenance
+
+This BNGL example was generated in BNG Playground and curated by Achyudhan.
+No external literature citation is associated with this model unless one is added manually.
+
+## Compatibility
+
+- BNG2 compatible: yes
+- Simulation methods: ode
+- Imported from: ai-generated
+
+## Files
+
+- ampk-signaling.bngl
+
+## Tags
+
+ampk, signaling, amp, lkb1, ca, sik, crtc