Merge pull request #9 from sybila/simplified-phenotype-control

Simplified phenotype control

Cargo.toml

@@ -17,8 +17,9 @@ clap = "4.0.26"
 serde_json = "1.0.59"
 itertools = "0.10.1"
 chrono = "0.4.19"
-biodivine-lib-bdd = ">=0.4.2, <1.0.0"
-biodivine-lib-param-bn = ">=0.4.1, <1.0.0"
+biodivine-lib-bdd = "0.4.*"
+biodivine-lib-param-bn = { git = "https://github.com/sybila/biodivine-lib-param-bn.git", branch =  "dev-faster-reach" }
+rstest = "0.17.0"
 
 [dev-dependencies]
 

README.md

@@ -8,6 +8,7 @@ The directory structure:
     ├── auxiliary_scripts    # Scripts to do & process experiments
     ├── models               # Base experimental models
     ├── results              # Raw measured results from experiments
+    ├── results_simple       # Raw measured results from experiments for simplified phenotype control procedure
     └── src                  # Library source code
 
 ### Auxiliary scripts
@@ -23,7 +24,11 @@ Base models for testing the library. Contains witness models from CellCollective
 
 ### Results
 
-The raw unprocessed outputs of experiments for both performance comparison and robustness metric.
+The raw unprocessed outputs of experiments for both performance comparison and robustness metric of one-step/temporary/permantent source-traget control.
+
+### Results
+
+The raw unprocessed outputs of experiments for phenotype control.
 
 ### src
 
@@ -37,8 +42,10 @@ Operations to perform base state-transition graph manipulations.
 
 Implementations of control algorithm on the perturbable graph.
 
+### phenotype_control
+
+Implementations of phenotype control algorithm on the perturbable graph.
+
 ### perturbation
 
 Data structure representing state transition graph of Boolean network which is viable for perturbations.  
-
-To run the basic experiments, execute `cargo run --release`

models_phenotype/[id-010]__[var-13]__[in-2]__[CARDIAC-DEVELOPMENT].aeon

@@ -0,0 +1,50 @@
+v_canWnt -> v_Mesp1
+v_exogen_BMP2_II -| v_Mesp1
+v_canWnt -> v_Isl1
+v_Fgf8 -> v_Isl1
+v_Tbx1 -> v_Isl1
+v_exogen_canWnt_II -> v_Isl1
+v_Mesp1 -> v_Isl1
+v_exogen_canWnt_II -> v_canWnt
+v_Bmp2 -> v_Nkx2_5
+v_Isl1 -> v_Nkx2_5
+v_Tbx1 -> v_Nkx2_5
+v_Dkk1 -> v_Nkx2_5
+v_Tbx5 -> v_Nkx2_5
+v_GATAs -> v_Nkx2_5
+v_Mesp1 -> v_Nkx2_5
+v_Nkx2_5 -> v_Tbx5
+v_canWnt -| v_Tbx5
+v_Dkk1 -| v_Tbx5
+v_Tbx1 -| v_Tbx5
+v_Tbx5 -? v_Tbx5
+v_Mesp1 -? v_Tbx5
+v_Tbx1 -> v_Fgf8
+v_Mesp1 -| v_Fgf8
+v_Foxc1_2 -> v_Fgf8
+v_canWnt -| v_Bmp2
+v_exogen_BMP2_II -> v_Bmp2
+v_canWnt -> v_Foxc1_2
+v_exogen_canWnt_II -> v_Foxc1_2
+v_canWnt -> v_Dkk1
+v_exogen_BMP2_II -| v_Dkk1
+v_Mesp1 -> v_Dkk1
+v_exogen_CanWnt_I -> v_exogen_canWnt_II
+v_exogen_BMP2_I -> v_exogen_BMP2_II
+v_Nkx2_5 -> v_GATAs
+v_Tbx5 -> v_GATAs
+v_Mesp1 -> v_GATAs
+v_Foxc1_2 -> v_Tbx1
+$v_Bmp2: (v_exogen_BMP2_II & !v_canWnt)
+$v_Dkk1: (v_Mesp1 | (v_canWnt & !v_exogen_BMP2_II))
+$v_Fgf8: ((v_Tbx1 & !v_Mesp1) | (v_Foxc1_2 & !v_Mesp1))
+$v_Foxc1_2: (v_canWnt & v_exogen_canWnt_II)
+$v_GATAs: ((v_Nkx2_5 | v_Tbx5) | v_Mesp1)
+$v_Isl1: (((v_Mesp1 | v_Tbx1) | v_Fgf8) | (v_canWnt & v_exogen_canWnt_II))
+$v_Mesp1: (v_canWnt & !v_exogen_BMP2_II)
+$v_Nkx2_5: ((((v_Tbx5 | v_Tbx1) | (v_Mesp1 & v_Dkk1)) | (v_Bmp2 & v_GATAs)) | (v_Isl1 & v_GATAs))
+$v_Tbx1: v_Foxc1_2
+$v_Tbx5: (((v_Tbx5 & !((v_canWnt | (v_Dkk1 & (!v_Tbx5 & !v_Mesp1))) | v_Tbx1)) | (v_Nkx2_5 & !((v_canWnt | (v_Dkk1 & (!v_Tbx5 & !v_Mesp1))) | v_Tbx1))) | (v_Mesp1 & !((v_canWnt | (v_Dkk1 & (!v_Tbx5 & !v_Mesp1))) | v_Tbx1)))
+$v_canWnt: v_exogen_canWnt_II
+$v_exogen_BMP2_II: v_exogen_BMP2_I
+$v_exogen_canWnt_II: v_exogen_CanWnt_I

models_phenotype/[id-014]__[var-54]__[in-7]__[T-LGL-SURVIVAL-NETWORK-2008].aeon

@@ -0,0 +1,247 @@
+v_PI3K -> v_NFAT
+v_Apoptosis -| v_NFAT
+v_TBET -> v_IFNGT
+v_NFAT -> v_IFNGT
+v_Apoptosis -| v_IFNGT
+v_STAT3 -> v_IFNGT
+v_Fas -> v_Ceramide
+v_S1P -| v_Ceramide
+v_Apoptosis -| v_Ceramide
+v_S1P -> v_GPCR
+v_Apoptosis -| v_GPCR
+v_NFKB -> v_FasT
+v_Apoptosis -| v_FasT
+v_FasT -> v_Fas
+v_FasL -> v_Fas
+v_Apoptosis -| v_Fas
+v_sFas -| v_Fas
+v_IFNG -> v_GZMB
+v_TBET -> v_GZMB
+v_CREB -> v_GZMB
+v_Apoptosis -| v_GZMB
+v_IFN -> v_CREB
+v_Apoptosis -| v_CREB
+v_ERK -> v_CREB
+v_FasT -> v_sFas
+v_Apoptosis -| v_sFas
+v_PDGFR -> v_SPHK1
+v_Apoptosis -| v_SPHK1
+v_IL2RB -> v_GRB2
+v_ZAP70 -> v_GRB2
+v_Apoptosis -| v_GRB2
+v_Stimuli -> v_IFNG
+v_P2 -| v_IFNG
+v_IFNGT -> v_IFNG
+v_SMAD -| v_IFNG
+v_IL2 -> v_IFNG
+v_Apoptosis -| v_IFNG
+v_IL15 -> v_IFNG
+v_PDGFR -> v_GAP
+v_RAS -> v_GAP
+v_IL2 -| v_GAP
+v_IL15 -| v_GAP
+v_Apoptosis -| v_GAP
+v_GAP -? v_GAP
+v_PDGFR -> v_PI3K
+v_RAS -> v_PI3K
+v_Apoptosis -| v_PI3K
+v_PDGF -> v_PDGFR
+v_S1P -> v_PDGFR
+v_Apoptosis -| v_PDGFR
+v_TBET -| v_IL2
+v_NFKB -> v_IL2
+v_NFAT -> v_IL2
+v_STAT3 -> v_IL2
+v_Apoptosis -| v_IL2
+v_RAS -> v_MEK
+v_Apoptosis -| v_MEK
+v_PI3K -> v_TPL2
+v_TNF -> v_TPL2
+v_TAX -> v_TPL2
+v_Apoptosis -| v_TPL2
+v_P27 -| v_Proliferation
+v_Apoptosis -| v_Proliferation
+v_STAT3 -> v_Proliferation
+v_IL2RB -> v_LCK
+v_CD45 -> v_LCK
+v_TCR -> v_LCK
+v_ZAP70 -| v_LCK
+v_Apoptosis -| v_LCK
+v_Apoptosis -| v_P27
+v_STAT3 -> v_P27
+v_GPCR -> v_SMAD
+v_Apoptosis -| v_SMAD
+v_Fas -> v_DISC
+v_FLIP -| v_DISC
+v_FasT -> v_DISC
+v_IL2 -> v_DISC
+v_Apoptosis -| v_DISC
+v_Ceramide -> v_DISC
+v_JAK -> v_SOCS
+v_IL2 -| v_SOCS
+v_IL15 -| v_SOCS
+v_Apoptosis -| v_SOCS
+v_A20 -| v_TRADD
+v_TNF -> v_TRADD
+v_Apoptosis -| v_TRADD
+v_IAP -| v_TRADD
+v_SPHK1 -> v_S1P
+v_Apoptosis -| v_S1P
+v_Ceramide -| v_S1P
+v_NFKB -> v_A20
+v_Apoptosis -| v_A20
+v_TCR -> v_CTLA4
+v_Apoptosis -| v_CTLA4
+v_Stimuli -> v_TCR
+v_CTLA4 -| v_TCR
+v_Apoptosis -| v_TCR
+v_TBET -> v_IL2RBT
+v_Apoptosis -| v_IL2RBT
+v_ERK -> v_IL2RBT
+v_PDGFR -> v_PLCG1
+v_Apoptosis -| v_PLCG1
+v_GRB2 -> v_PLCG1
+v_FLIP -> v_NFKB
+v_PI3K -> v_NFKB
+v_TRADD -> v_NFKB
+v_TPL2 -> v_NFKB
+v_Apoptosis -| v_NFKB
+v_IAP -> v_NFKB
+v_DISC -> v_Caspase
+v_TRADD -> v_Caspase
+v_GZMB -> v_Caspase
+v_Apoptosis -| v_Caspase
+v_BID -> v_Caspase
+v_IAP -| v_Caspase
+v_IL2RA -| v_IL2RA
+v_IL2RAT -> v_IL2RA
+v_IL2 -> v_IL2RA
+v_Apoptosis -| v_IL2RA
+v_NFKB -> v_BclxL
+v_DISC -| v_BclxL
+v_GZMB -| v_BclxL
+v_Apoptosis -| v_BclxL
+v_STAT3 -> v_BclxL
+v_BID -| v_BclxL
+v_TBET -> v_TBET
+v_JAK -> v_TBET
+v_Apoptosis -| v_TBET
+v_BclxL -| v_BID
+v_GZMB -> v_BID
+v_Apoptosis -| v_BID
+v_Caspase -> v_BID
+v_MCL1 -| v_BID
+v_NFKB -> v_TNF
+v_Apoptosis -| v_TNF
+v_IL2RBT -> v_IL2RB
+v_IL2 -> v_IL2RB
+v_IL15 -> v_IL2RB
+v_Apoptosis -| v_IL2RB
+v_PLCG1 -> v_RAS
+v_Apoptosis -| v_RAS
+v_GRB2 -> v_RAS
+v_GAP -| v_RAS
+v_NFKB -> v_RANTES
+v_Apoptosis -| v_RANTES
+v_JAK -> v_STAT3
+v_Apoptosis -| v_STAT3
+v_Apoptosis -? v_Apoptosis
+v_Caspase -> v_Apoptosis
+v_IL2RB -> v_FYN
+v_TCR -> v_FYN
+v_Apoptosis -| v_FYN
+v_IFNG -> v_FLIP
+v_DISC -| v_FLIP
+v_NFKB -> v_FLIP
+v_CREB -> v_FLIP
+v_Apoptosis -| v_FLIP
+v_NFKB -> v_FasL
+v_NFAT -> v_FasL
+v_Apoptosis -| v_FasL
+v_STAT3 -> v_FasL
+v_ERK -> v_FasL
+v_FYN -> v_Cytoskeleton_signaling
+v_Apoptosis -| v_Cytoskeleton_signaling
+v_MEK -> v_ERK
+v_PI3K -> v_ERK
+v_Apoptosis -| v_ERK
+v_NFKB -> v_IAP
+v_Apoptosis -| v_IAP
+v_BID -| v_IAP
+v_IFNG -> v_P2
+v_P2 -? v_P2
+v_Apoptosis -| v_P2
+v_Stimuli2 -| v_P2
+v_IL2RB -> v_MCL1
+v_PI3K -> v_MCL1
+v_NFKB -> v_MCL1
+v_STAT3 -> v_MCL1
+v_Apoptosis -| v_MCL1
+v_FYN -| v_ZAP70
+v_Apoptosis -| v_ZAP70
+v_LCK -> v_ZAP70
+v_IFNG -> v_JAK
+v_IL2RA -> v_JAK
+v_IL2RB -> v_JAK
+v_CD45 -| v_JAK
+v_RANTES -> v_JAK
+v_SOCS -| v_JAK
+v_Apoptosis -| v_JAK
+v_NFKB -> v_IL2RAT
+v_IL2 -> v_IL2RAT
+v_Apoptosis -| v_IL2RAT
+v_STAT3 -> v_IL2RAT
+$v_A20: (v_NFKB & !v_Apoptosis)
+$v_Apoptosis: (v_Caspase | v_Apoptosis)
+$v_BID: ((v_GZMB & !((v_BclxL | v_Apoptosis) | v_MCL1)) | (v_Caspase & !((v_BclxL | v_Apoptosis) | v_MCL1)))
+$v_BclxL: ((v_NFKB & !(((v_BID | v_DISC) | v_Apoptosis) | v_GZMB)) | (v_STAT3 & !(((v_BID | v_DISC) | v_Apoptosis) | v_GZMB)))
+$v_CREB: ((v_ERK & v_IFN) & !v_Apoptosis)
+$v_CTLA4: (v_TCR & !v_Apoptosis)
+$v_Caspase: ((((v_TRADD & v_BID) & !(v_IAP | v_Apoptosis)) | ((v_GZMB & v_BID) & !(v_IAP | v_Apoptosis))) | (v_DISC & !v_Apoptosis))
+$v_Ceramide: (v_Fas & !(v_Apoptosis | v_S1P))
+$v_Cytoskeleton_signaling: (v_FYN & !v_Apoptosis)
+$v_DISC: ((v_FasT & (((v_Fas & v_IL2) | (v_Fas & !v_FLIP)) | v_Ceramide)) & !v_Apoptosis)
+$v_ERK: ((v_MEK & v_PI3K) & !v_Apoptosis)
+$v_FLIP: ((v_NFKB & !(v_Apoptosis | v_DISC)) | ((v_CREB & v_IFNG) & !(v_Apoptosis | v_DISC)))
+$v_FYN: ((v_IL2RB & !v_Apoptosis) | (v_TCR & !v_Apoptosis))
+$v_Fas: ((v_FasT & v_FasL) & !(v_Apoptosis | v_sFas))
+$v_FasL: ((((v_NFAT & !v_Apoptosis) | (v_NFKB & !v_Apoptosis)) | (v_STAT3 & !v_Apoptosis)) | (v_ERK & !v_Apoptosis))
+$v_FasT: (v_NFKB & !v_Apoptosis)
+$v_GAP: (((v_PDGFR & v_GAP) & !((v_IL2 | v_IL15) | v_Apoptosis)) | (v_RAS & !((v_IL2 | v_IL15) | v_Apoptosis)))
+$v_GPCR: (v_S1P & !v_Apoptosis)
+$v_GRB2: ((v_ZAP70 & !v_Apoptosis) | (v_IL2RB & !v_Apoptosis))
+$v_GZMB: ((v_TBET & !v_Apoptosis) | ((v_CREB & v_IFNG) & !v_Apoptosis))
+$v_IAP: (v_NFKB & !(v_BID | v_Apoptosis))
+$v_IFNG: ((((v_IL15 & v_IFNGT) & !((v_SMAD | v_Apoptosis) | v_P2)) | ((v_Stimuli & v_IFNGT) & !((v_SMAD | v_Apoptosis) | v_P2))) | ((v_IL2 & v_IFNGT) & !((v_SMAD | v_Apoptosis) | v_P2)))
+$v_IFNGT: (((v_NFAT & !v_Apoptosis) | (v_TBET & !v_Apoptosis)) | (v_STAT3 & !v_Apoptosis))
+$v_IL2: (((v_STAT3 & !(v_TBET | v_Apoptosis)) | (v_NFAT & !(v_TBET | v_Apoptosis))) | (v_NFKB & !(v_TBET | v_Apoptosis)))
+$v_IL2RA: ((v_IL2 & v_IL2RAT) & !(v_IL2RA | v_Apoptosis))
+$v_IL2RAT: ((v_IL2 & (v_NFKB | v_STAT3)) & !v_Apoptosis)
+$v_IL2RB: ((v_IL2RBT & (v_IL2 | v_IL15)) & !v_Apoptosis)
+$v_IL2RBT: ((v_ERK & v_TBET) & !v_Apoptosis)
+$v_JAK: ((((v_IL2RA & !((v_SOCS | v_Apoptosis) | v_CD45)) | (v_IFNG & !((v_SOCS | v_Apoptosis) | v_CD45))) | (v_IL2RB & !((v_SOCS | v_Apoptosis) | v_CD45))) | (v_RANTES & !((v_SOCS | v_Apoptosis) | v_CD45)))
+$v_LCK: (((v_IL2RB & !(v_ZAP70 | v_Apoptosis)) | (v_TCR & !(v_ZAP70 | v_Apoptosis))) | (v_CD45 & !v_Apoptosis))
+$v_MCL1: ((v_IL2RB & ((v_PI3K & v_NFKB) & v_STAT3)) & !v_Apoptosis)
+$v_MEK: (v_RAS & !v_Apoptosis)
+$v_NFAT: (v_PI3K & !v_Apoptosis)
+$v_NFKB: (((v_TPL2 & !v_Apoptosis) | (v_PI3K & !v_Apoptosis)) | ((v_FLIP & (v_TRADD & v_IAP)) & !v_Apoptosis))
+$v_P2: ((v_IFNG & !(v_Stimuli2 | v_Apoptosis)) | (v_P2 & !(v_Stimuli2 | v_Apoptosis)))
+$v_P27: (v_STAT3 & !v_Apoptosis)
+$v_PDGFR: ((v_S1P & !v_Apoptosis) | (v_PDGF & !v_Apoptosis))
+$v_PI3K: ((v_PDGFR & !v_Apoptosis) | (v_RAS & !v_Apoptosis))
+$v_PLCG1: ((v_PDGFR & !v_Apoptosis) | (v_GRB2 & !v_Apoptosis))
+$v_Proliferation: (v_STAT3 & !(v_Apoptosis | v_P27))
+$v_RANTES: (v_NFKB & !v_Apoptosis)
+$v_RAS: ((v_PLCG1 & !(v_Apoptosis | v_GAP)) | (v_GRB2 & !(v_Apoptosis | v_GAP)))
+$v_S1P: (v_SPHK1 & !(v_Apoptosis | v_Ceramide))
+$v_SMAD: (v_GPCR & !v_Apoptosis)
+$v_SOCS: (v_JAK & !((v_IL15 | v_IL2) | v_Apoptosis))
+$v_SPHK1: (v_PDGFR & !v_Apoptosis)
+$v_STAT3: (v_JAK & !v_Apoptosis)
+$v_TBET: ((v_JAK & !v_Apoptosis) | (v_TBET & !v_Apoptosis))
+$v_TCR: (v_Stimuli & !(v_CTLA4 | v_Apoptosis))
+$v_TNF: (v_NFKB & !v_Apoptosis)
+$v_TPL2: (((v_PI3K & v_TNF) & !v_Apoptosis) | (v_TAX & !v_Apoptosis))
+$v_TRADD: (v_TNF & !((v_IAP | v_A20) | v_Apoptosis))
+$v_ZAP70: (v_LCK & !(v_Apoptosis | v_FYN))
+$v_sFas: (v_FasT & !v_Apoptosis)