Alzheimers_Buildup

globals [CellState]                                                       ;; keep track of CellState

Breed [NFT a-NFT ]
NFT-own [energyNFT]                                                       ;; AB, NFT, and APOE2 are all breeds of turtle.

Breed [ AB a-AB ]
AB-own [energyAB]

Breed [ APOE APOEsingle]
APOE-own [energyAPOE birth]

patches-own [countdown dead ]

to setup
  clear-all

  ask patches [
    set countdown DiseaseProgression ]                                    ;; initialize CellState to set parameter

  set-default-shape NFT "circle"
  create-NFT NFT-buildup [                                                ;; create the NFT, then initialize their variables
    set color magenta
    set size 2.3                                                          ;; NFT can be up to 441 amino acids long (Sontheimer, 2015), using the 352 isoform, 352/150 = 2.3
    set label-color magenta - 2
    set energyNFT 50
    setxy random-xcor random-ycor ]

  set-default-shape AB "circle"
  create-AB AB-buildup [                                                  ;; create the AB, then initialize their variables
    set color blue
    set size .5                                                           ;; AB is up to 51 amino acids long (Olsson, 2014), 51/200 = .333, round up to .5
    set label-color blue - 2
    set energyAB 50
    setxy random-xcor random-ycor ]

  set-default-shape APOE "square"
  create-APOE Inital-APOE [                                               ;; create the APOE, then initialize their variables
    set color red
    set size 2                                                            ;; APOE is 299 amino acids long  (Phillips, 2014), 299/150 = 2
    set energyAPOE 100
    setxy random-xcor random-ycor ]

  reset-ticks
end 

to go
  if not any? APOE [ stop ]                                               ;; Humans require APOE for survival
  if (((count patches with [pcolor = green]) * 100)/(count patches) < %LiveRequired? ) [ stop]  ;; Humans require live cells

  ask NFT [                                                               ;; NFT is intracellular, does not move, does not lose energy
    task-CellState
    transcribe-NFT ]

  ask AB [
    move
    set energyAB energyAB - .25                                           ;; AB loses energy as it moves
    task-CellState
    transcribe-AB ]

  ask APOE [
    move
    set energyAPOE energyAPOE - 1                                         ;; APOE requires more energy than AB to move, larger
    set birth 1
    catch
    deathAPOE
    transcribe-APOE ]

  ask patches [ grow-CellState ]                                          ;; run procedure to allow regrowth of Cell health

  tick
end 

to move                                                                   ;; turtle moving around procedure
  rt random 100
  lt random 100
  fd 1
end 

to task-CellState                                                         ;; task CellState
  ask NFT-here [
    if pcolor = green [
    set pcolor brown                                                      ;; turn the cell brown, indicating cell recovering from task performed
    set energyNFT energyNFT + 5                                           ;; NFT and AB gain energy by performing tasks on each cell
      if energyNFT < 0 and pcolor = brown [ die ] ] ]                     ;; if NFT or AB run out of energy on an already unhealthy cell, die

  ask AB-here [
    if pcolor = green [                                                   ;; same thing, for AB
    set pcolor brown
    set energyAB energyAB + 100
      if energyAB < 0 and pcolor = brown [ die ] ] ]
end 

to catch
 let preyAB one-of AB-here                                                ;; AB procedure, grab a random AB
  if (preyAB != nobody)                                                   ;; did we get one? if so,
  [ if (APOE-Variant = "APOE2" ) and (random-float 50 < AB-Transcription-Level ) ;; APOE2 has better odds of binding than APOE3 or APOE4
     [ ask preyAB [ die ]                                                 ;; kill it
      set energyAPOE energyAPOE + 50 ]                                    ;; get energy from breaking down AB

    if (APOE-Variant = "APOE3" ) and (random-float 75 < AB-Transcription-Level )
      [ ask preyAB [ die ]                                                ;; APOE3 and APOE4 are progressively worse at binding AB, get less energy from it
      set energyAPOE energyAPOE + 35 ]

    if (APOE-Variant = "APOE4" ) and (random-float 100 < AB-Transcription-Level )
      [ ask preyAB [ die ]                                                ;; APOE3 and APOE4 are progressively worse at binding AB, get less energy from it
      set energyAPOE energyAPOE + 20 ] ]                                  ;; APOE3 and APOE4 allow higher levels of waste accumulation

  if count AB > 1                                                         ;; APOE only acts on NFT when AB is present (Farfel, 2016)
   [let preyNFT one-of NFT-here                                           ;; same as above for NFT
    if (preyNFT != nobody)
  [ if (APOE-Variant = "APOE2" ) and (random-float 50 < NFT-Transcription-Level )
     [ ask preyNFT [ die ]
      set energyAPOE energyAPOE + 50 ]

    if ( APOE-Variant = "APOE3" ) and (random-float 75 < NFT-Transcription-Level )
    [ ask preyNFT [ die ]
      set energyAPOE energyAPOE + 35 ]

    if (APOE-Variant = "APOE4" ) and (random-float 100 < NFT-Transcription-Level )
    [ ask preyNFT [ die ]
        set energyAPOE energyAPOE + 20 ] ] ]
end 

to transcribe-NFT                                                          ;; NFT procedure
  if count AB > 1   [                                                      ;; AB cascade hypothesis (Jack, 2011)
    if random-float 100 < ( NFT-Transcription-Level / 25 ) [               ;; throw "dice" to see if you will transcribe
      set energyNFT (energyNFT / 2)                                        ;; divide energy between parent and offspring
        hatch 1 [ rt random-float 360 fd 3 ] ] ]                           ;; hatch an offspring and move it forward 5 steps
end 

to transcribe-AB                                                           ;; AB procedure
  if random-float 50 < ( AB-Transcription-Level / 25 ) [                   ;; throw "dice" to see if you will transcribe, odds are better to compensate for NFT being larger/more accessible to APOE
    set energyAB (energyAB / 2)                                            ;; divide energy between parent and offspring
      hatch 1 [ rt random-float 360 fd 1 ] ]                               ;; hatch an offspring and move it forward 1 step
end 

to transcribe-APOE                                                         ;; APOE procedure
  ifelse ( count APOE < ( count NFT + count AB) ) [                        ;; transcribe more APOE only if NFT and AB levels are too high
     if (random-float 100 < ( APOE-Transcription-Level / 25 ))             ;; throw "dice" to see if you will transcribe
     [set energyAPOE (energyAPOE / 2)                                      ;; divide energy between parent and offspring
      hatch 1 [ rt random-float 360 fd 1]                                  ;; hatch an offspring and move it forward 1 step
      if pcolor = green
       [set pcolor brown
          set energyAPOE energyAPOE + 5 ] ] ]                              ;; APOE gets energy from cell as it is transcribed, takes cell's health for itself

     [ die ]                                                               ;; if ( APOE > NFT + AB) too much APOE already, cells will degrade APOE not produce more
end 

to deathAPOE                                                               ;; APOE procedure when energy dips, die
  if APOE-Variant = "APOE2" [ if energyAPOE < 0 [ die ]  ]                 ;; APOE2 is the baseline
  if APOE-Variant = "APOE3" [ if energyAPOE < 5 [ die ]  ]                 ;; APOE3 and APOE4 are worse adapted to survival, die faster
  if APOE-Variant = "APOE4" [ if energyAPOE < 10 [ die ]  ]
end 

to grow-CellState                                                          ;; countdown on brown patches: if reach 0, grow some CellState
    if pcolor = brown [
      ifelse countdown <= 0
        [ set pcolor green
          set countdown DiseaseProgression ]
        [   if APOE-Variant = "APOE2" [ set countdown countdown - 10 ]     ;; APOE2 is the baseline, cell recover faster
            if APOE-Variant = "APOE3" [ set countdown countdown - 5  ]     ;; APOE3 and APOE4 are harder on the cells, cells take longer to recover
            if APOE-Variant = "APOE4" [ set countdown countdown - 1  ] ] ]
end 

to color-patches                                                           ;; sets the disease state - user inputs how 'healthy' the tissue begins
         let InitalLivePatches (100 - DiseaseProgression)
         let total InitalLivePatches + DiseaseProgression
         let p-green InitalLivePatches / total
         let p-brown DiseaseProgression / total
      ask patches [
         let x random-float 1.0
         if x <= p-green + p-brown [ set pcolor green]
         if x <= p-brown [ set pcolor brown] ]
end