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pluto_gui_orig_and_split.jl
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pluto_gui_orig_and_split.jl
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### A Pluto.jl notebook ###
# v0.19.36
using Markdown
using InteractiveUtils
# This Pluto notebook uses @bind for interactivity. When running this notebook outside of Pluto, the following 'mock version' of @bind gives bound variables a default value (instead of an error).
macro bind(def, element)
quote
local iv = try Base.loaded_modules[Base.PkgId(Base.UUID("6e696c72-6542-2067-7265-42206c756150"), "AbstractPlutoDingetjes")].Bonds.initial_value catch; b -> missing; end
local el = $(esc(element))
global $(esc(def)) = Core.applicable(Base.get, el) ? Base.get(el) : iv(el)
el
end
end
# ╔═╡ 4c9c24cc-b865-4825-a841-f717120d27d2
begin
using Pkg
Pkg.activate(".")
using Colors
using AlgebraicPetri
using Catlab
using GraphViz
using JSON
using DataFrames
using CSV
using XLSX
end
# ╔═╡ 32c8703f-6aa3-46be-a91b-ff36225d6bd8
module EnzymeReactions
using AlgebraicPetri
using Catlab.Programs
using Catlab.Graphics
using Catlab.WiringDiagrams
using Catlab.CategoricalAlgebra
using Distributions
using DifferentialEquations
using Plots
using Plots.PlotMeasures
export ob, ode,
inactivate, bindunbind, degrade,
enzX, enzXY, enzXsubY,
enz, enz_enz, enz_sub,
enzyme_uwd, enzyme_generators
sep_sym = "↦"
ob(type, x) = codom(Open([first(x)], LabelledReactionNet{type,Number}(x), [first(x)])).ob;
ob(x) = codom(Open([x], LabelledPetriNet(x), [x])).ob;
ode(x::Union{AbstractReactionNet{Distribution, Number},AbstractLabelledReactionNet{Distribution, Number}}, t) = begin
β = mean.(rates(x))
ODEProblem(vectorfield(x), concentrations(x), t, β)
end
ode(x, t) = ODEProblem(vectorfield(x), concentrations(x), t, rates(x));
function inactivate(in,on::T) where T
inact = Symbol(first(in), :_inact)
Open(LabelledReactionNet{T,Number}(unique((in, inact=>0)), ((Symbol(:inact_,first(in)),on),first(in)=>inact)))
end;
function bindunbind(in1, in2, on::T, off::T) where T
out = Symbol(first(in1), sep_sym,first(in2))
Open(LabelledReactionNet{T,Number}(unique((in1, in2,out=>0)), ((Symbol(:bind_,first(in1), sep_sym,first(in2)),on),(first(in1),first(in2))=>out),
((Symbol(:unbind_,out),off),out=>(first(in1),first(in2)))))
end;
function degrade(prod1,prod2,on::T) where T
in = Symbol(first(prod1), sep_sym,first(prod2))
prod2str = String(first(prod2))
degprod2 = Symbol(endswith(prod2str, "inact") ? first(prod2str) : prod2str, :_deg)
Open(LabelledReactionNet{T,Number}(unique((in=>0, prod1,degprod2=>0)), ((Symbol(:deg_,in),on),in=>(first(prod1),degprod2))));
end;
function inactivate(in)
inact = Symbol(in, :_inact)
Open(LabelledPetriNet(unique((in, inact)), (Symbol(:inact_,in),in=>inact)))
end;
function bindunbind(in1, in2)
out = Symbol(in1, sep_sym,in2)
Open(LabelledPetriNet(unique((in1, in2,out)), (Symbol(:bind_,in1, sep_sym,in2),(in1,in2)=>out),
(Symbol(:unbind_,out),out=>(in1,in2))))
end;
function degrade(prod1,prod2)
in = Symbol(prod1, sep_sym,prod2)
prod2str = String(prod2)
degprod2 = Symbol(endswith(prod2str, "inact") ? first(prod2str) : prod2str, :_deg)
Open(LabelledPetriNet(unique((in, prod1,degprod2)), (Symbol(:deg_,in),in=>(prod1,degprod2))));
end;
# ## Cathepsin *X* reacting with itself
enzX = @relation (X, Xinact, Xdeg) where (X, Xinact, Xdeg, XX, XXinact) begin
inactX(X, Xinact)
bindXX(X, XX)
degXX(XX, X, Xdeg)
bindXXinact(X, Xinact, XXinact)
degXXinact(XXinact, X, Xdeg)
end
# ## Cathepsin *X* reacting with Substrate *Y*
enzXsubY = @relation (X, Xinact, Xdeg, Y, Ydeg) where (X, Xinact, Xdeg, Y, XY, Ydeg) begin
bindXY(X, Y, XY)
degXY(XY, X, Ydeg)
end
# ## Cathepsin *X* reacting with Cathepsin *Y*
enzXY = @relation (X, Xinact, Xdeg, Y, Yinact, Ydeg) where (X, Xinact, Xdeg, Y, Yinact, Ydeg, XY, XYinact) begin
bindXY(X, Y, XY)
degXY(XY, X, Ydeg)
bindXYinact(X, Yinact, XYinact)
degXYinact(XYinact, X, Ydeg)
end
function enz(rxns, cat)
catsym = first(cat)
obtype = valtype(rates(apex(first(last(first(rxns))))))
out = oapply(enzX, Dict([:inactX, :bindXX, :degXX, :bindXXinact, :degXXinact] .=> rxns[catsym]), Dict(
:X=>ob(obtype, cat),
:Xinact=>ob(obtype, Symbol(catsym,:_inact)=>0),
:Xdeg=>ob(obtype, Symbol(catsym,:_deg)=>0),
:XX=>ob(obtype, Symbol(catsym, sep_sym,catsym)=>0),
:XXinact=>ob(obtype, Symbol(catsym, sep_sym,catsym,:_inact)=>0)))
bundle_legs(out, [[1,2,3]])
end
function enz_sub(rxns, cat1, sub)
catsym = first(cat1)
subsym = first(sub)
catsub = Symbol(catsym, sep_sym, subsym)
obtype = valtype(rates(apex(first(last(first(rxns))))))
out = oapply(enzXsubY, Dict([:bindXY, :degXY] .=> rxns[catsub]), Dict(
:X=>ob(obtype, cat1),
:Xinact=>ob(obtype, Symbol(catsym,:_inact)=>0),
:Xdeg=>ob(obtype, Symbol(catsym,:_deg)=>0),
:Y=>ob(obtype, sub),
:XY=>ob(obtype, Symbol(catsym,sep_sym,subsym)=>0),
:Ydeg=>ob(obtype, Symbol(subsym,:_deg)=>0)))
bundle_legs(out, [[1,2,3], [4,5]])
end
function enz_enz(rxns, cat1, cat2)
cat1sym = first(cat1)
cat2sym = first(cat2)
catcat = Symbol(cat1sym, sep_sym, cat2sym)
obtype = valtype(rates(apex(first(last(first(rxns))))))
out = oapply(enzXY, Dict([:bindXY, :degXY, :bindXYinact, :degXYinact] .=> rxns[catcat]), Dict(
:X=>ob(obtype, cat1),
:Xinact=>ob(obtype, Symbol(cat1sym,:_inact)=>0),
:Xdeg=>ob(obtype, Symbol(cat1sym,:_deg)=>0),
:Y=>ob(obtype, cat2),
:Yinact=>ob(obtype, Symbol(cat2sym,:_inact)=>0),
:Ydeg=>ob(obtype, Symbol(cat2sym,:_deg)=>0),
:XY=>ob(obtype, catcat=>0),
:XYinact=>ob(obtype, Symbol(catcat,:_inact)=>0)))
bundle_legs(out, [[1,2,3], [4,5,6]])
end
function enz(cat::Symbol)
catsym = cat
out = oapply(enzX, Dict(:inactX=>inactivate(cat), :bindXX=>bindunbind(cat, cat), :degXX=>degrade(cat, cat),
:bindXXinact=>bindunbind(cat, Symbol(cat,:_inact)),
:degXXinact=>degrade(cat, Symbol(cat, :_inact))), Dict(
:X=>ob(cat),
:Xinact=>ob(Symbol(catsym,:_inact)),
:Xdeg=>ob(Symbol(catsym,:_deg)),
:XX=>ob(Symbol(catsym, sep_sym,catsym)),
:XXinact=>ob(Symbol(catsym, sep_sym,catsym,:_inact))))
bundle_legs(out, [[1,2,3]])
end
function enz_sub(cat1::Symbol, sub::Symbol)
catsym = cat1
subsym = sub
catsub = Symbol(catsym, sep_sym, subsym)
out = oapply(enzXsubY, Dict(:bindXY=>bindunbind(cat1, sub), :degXY=>degrade(cat1, sub)), Dict(
:X=>ob(cat1),
:Xinact=>ob(Symbol(catsym,:_inact)),
:Xdeg=>ob(Symbol(catsym,:_deg)),
:Y=>ob(sub),
:XY=>ob(Symbol(catsym, sep_sym,subsym)),
:Ydeg=>ob(Symbol(subsym,:_deg))))
bundle_legs(out, [[1,2,3], [4,5]])
end
function enz_enz(cat1::Symbol, cat2::Symbol)
cat1sym = cat1
cat2sym = cat2
catcat = Symbol(cat1sym, sep_sym, cat2sym)
out = oapply(enzXY, Dict(:bindXY=>bindunbind(cat1, cat2), :degXY=>degrade(cat1, cat2), :bindXYinact=>bindunbind(cat1, Symbol(cat2, :_inact)), :degXYinact=>degrade(cat1, Symbol(cat2, :_inact))), Dict(
:X=>ob(cat1),
:Xinact=>ob(Symbol(cat1sym,:_inact)),
:Xdeg=>ob(Symbol(cat1sym,:_deg)),
:Y=>ob(cat2),
:Yinact=>ob(Symbol(cat2sym,:_inact)),
:Ydeg=>ob(Symbol(cat2sym,:_deg)),
:XY=>ob(catcat),
:XYinact=>ob(Symbol(catcat,:_inact))))
bundle_legs(out, [[1,2,3], [4,5,6]])
end
function enzyme_uwd(enzymes::Array{Symbol}, substrates::Array{Symbol})
rel = RelationDiagram{Symbol}(0)
chemicals = vcat(substrates, enzymes)
subs = add_junctions!(rel, length(substrates), variable=substrates)
enzs = add_junctions!(rel, length(enzymes), variable=enzymes)
nsubs = length(subs)
nenzs = length(enzs)
catx = add_parts!(rel, :Box, nenzs, name=[Symbol("cat$i") for i in enzymes])
add_parts!(rel, :Port, nenzs, junction=enzs, box=catx)
for x in 1:nenzs
for y in 1:nenzs
if y != x
catxy = add_part!(rel, :Box, name=Symbol("cat$(enzymes[x])cat$(enzymes[y])"))
add_parts!(rel, :Port, 2, junction=[enzs[x], enzs[y]], box=catxy)
end
end
end
for x in 1:nenzs
for y in 1:nsubs
catxy = add_part!(rel, :Box, name=Symbol("cat$(enzymes[x])sub$(substrates[y])"))
add_parts!(rel, :Port, 2, junction=[enzs[x], subs[y]], box=catxy)
end
end
add_parts!(rel, :OuterPort, length(chemicals), outer_junction = vcat(subs, enzs))
rel
end
function enzyme_generators(enzymes::Array{Symbol}, substrates::Array{Symbol})
gens = Dict{Symbol, Any}()
for e1 in enzymes
for e2 in enzymes
if e1 == e2
gens[Symbol(:cat, e1)] = enz(e1)
else
gens[Symbol(:cat, e1, :cat, e2)] = enz_enz(e1, e2)
end
end
for s in substrates
gens[Symbol(:cat, e1, :sub, s)] = enz_sub(e1, s)
end
end
gens
end
end
# ╔═╡ db1cf041-8f29-4433-a8b7-da5ea4828d52
Pkg.resolve()
# ╔═╡ aa5b099e-771f-42ff-a1b1-d22f0e615395
# ╔═╡ 178e764e-e239-4689-bb2f-4993b7755724
import .EnzymeReactions: ob, ode,
inactivate, bindunbind, degrade,
enzX, enzXY, enzXsubY,
enz, enz_enz, enz_sub,
enzyme_uwd, enzyme_generators
# ╔═╡ 563cf0a2-80e0-4bc2-8f6f-6a47cb2112af
@present ThAffinityNet(FreeSchema) begin
(Rxn, Species)::Ob
(Rate, Label)::Data
binder::Hom(Rxn, Species)
bindee::Hom(Rxn, Species)
affinity::Attr(Rxn, Rate)
family::Attr(Species, Label)
form::Attr(Species, Label)
end;
# ╔═╡ 2d89b8e5-31a0-402c-b95c-87494a5a1317
begin
const AbstractAffinityNet = AbstractACSetType(ThAffinityNet)
const AffinityNet = ACSetType(ThAffinityNet){Real, Symbol}
function migrate_species!(an::AffinityNet, ln::LabelledReactionNet, index::Int64)
labels = Symbol.(split(string(ln[index, :sname]), "_"))
if length(labels) == 1
push!(labels, :norm)
end
@assert (length(labels) == 2) begin
error("Label \"$(ln[index,:sname])\" is not in a valid format (family_form)")
end
add_part!(an, :Species, family=labels[1], form=labels[2])
end
function AffinityNet(ln::LabelledReactionNet{R, C}) where {R,C}
# Collect associative/dissociative pairs
assoc = Dict{Int64, Array{Tuple{Int64, Int64, Int64},1}}()
dissoc = Dict{Int64, Array{Tuple{Int64, Int64, Int64},1}}()
for o in 1:nparts(ln, :T)
outputs = ln[incident(ln, o, :ot), :os]
inputs = ln[incident(ln, o, :it), :is]
if length(outputs) == 2 && length(inputs) == 1
if !(inputs[1] in keys(dissoc))
dissoc[inputs[1]] = Array{Tuple{Int64, Int64, Int64},1}()
end
push!(dissoc[inputs[1]], outputs[1] < outputs[2] ? (outputs[1], outputs[2], o) :
(outputs[2], outputs[1], o))
elseif length(inputs) == 2 && length(outputs) == 1
if !(outputs[1] in keys(assoc))
assoc[outputs[1]] = Array{Tuple{Int64, Int64, Int64},1}()
end
push!(assoc[outputs[1]], inputs[1] < inputs[2] ? (inputs[1], inputs[2], o) :
(inputs[2], inputs[1], o))
end
end
# Generate affinity net from pairs
an = AffinityNet()
s2i = Dict{Int64, Int64}()
for prod in keys(assoc)
if prod in keys(dissoc)
for j in 1:length(assoc[prod])
for i in 1:length(dissoc[prod])
if assoc[prod][j][[1,2]] == dissoc[prod][i][[1,2]]
ls, rs = ln[incident(ln, assoc[prod][j][3], :it), :is]
ar, dr = (ln[assoc[prod][j][3], :rate], ln[dissoc[prod][i][3], :rate])
if !(ls in keys(s2i))
s2i[ls] = migrate_species!(an, ln, ls)
end
if !(rs in keys(s2i))
s2i[rs] = migrate_species!(an, ln, rs)
end
add_part!(an, :Rxn, binder=s2i[ls], bindee=s2i[rs], affinity=ar/dr)
end
end
end
end
end
an
end
function propertygraph(an::AffinityNet;
prog::AbstractString="neato", graph_attrs::AbstractDict=Dict(),
node_attrs::AbstractDict=Dict(), edge_attrs::AbstractDict=Dict(:len=>"2.0"),
node_labels::Bool=true, edge_labels::Bool=false)
shapes = ["box", "circle", "triangle", "diamond", "pentagon", "hexagon", "septagon", "octagon"]
families = unique(an[:family])
forms = unique(an[:form])
colors = string.(hex.(distinguishable_colors(length(forms), [RGB(1,1,1),RGB(0,0,0)], dropseed=true)))
fam2shp = Dict(families[i]=>shapes[i] for i in 1:length(families))
frm2clr = Dict(forms[i]=>colors[i] for i in 1:length(forms))
rates = an[:affinity]
minrate, maxrate = (minimum(rates), maximum(rates))
rate_to_width(rate) = begin
0.1 + (log(rate) - log(minrate)) * (2/(log(maxrate)-log(minrate)))
end
node_labeler(v) = begin
Dict(:label=>"$(an[v,:family])$(an[v,:form]==:norm ? "" : Symbol("_",an[v,:form]))",
:style=>"filled",
:width=>"0.75", :height=>"0.75", :fixedsize=>"false",
:shape=>fam2shp[an[v,:family]],
:fillcolor=>"#$(frm2clr[an[v,:form]])")
end
edge_labeler(e) = begin
return Dict(:color=>"black", :penwidth=>"$(round(rate_to_width(an[e,:affinity]), digits=1))")
end
g = Catlab.Graphs.Graph()
migrate!(g, an, Dict(:V=>:Species, :E=>:Rxn), Dict(:tgt=>:bindee, :src=>:binder))
Catlab.Graphs.PropertyGraph{Any}(g, node_labeler, edge_labeler;
prog = prog,
graph = merge!(Dict(:rankdir => "TB"), graph_attrs),
node = merge!(Graphics.GraphvizGraphs.default_node_attrs(node_labels), node_attrs),
edge = merge!(Dict(:arrowsize => "0.5"), edge_attrs),
)
end
function Graphics.to_graphviz(an::AffinityNet; kwargs...)
propertygraph(an; kwargs...) |> to_graphviz
end
end
# ╔═╡ 3779b846-e5ec-4239-a1d4-af2f8c2f10eb
begin
using PlutoUI
using LabelledArrays
using DifferentialEquations
using Plots
plotly()
display_uwd(ex) = to_graphviz(ex, box_labels=:name, junction_labels=:variable, edge_attrs=Dict(:len=>".75"));
nothing
end
# ╔═╡ 93df89f0-8429-4fcc-bd01-6982417f5134
begin
# Initial Concentrations
K = :K=>33000;
S = :S=>33000;
L = :L=>33000;
Kinact = :K_inact=>0;
Sinact = :S_inact=>0;
Linact = :L_inact=>0;
E = :E=>700000;
G = :G=>714000;
Spike = :Spike=>66000;
cats = [:K, :S, :L]
subs = [:E, :G, :Spike]
# Parameter Rates (units of pM and min)
rxns = Dict(
"K" => [inactivate(K, 7.494e-10)
bindunbind(K, K, 7.814e-4, 3.867e-3)
degrade(K, K, 2.265e-1)
bindunbind(K, Kinact, 7.814e-4, 3.867e-3)
degrade(K, Kinact, 2.265e-1)],
"S" => [inactivate(S, 1.906e-2)
bindunbind(S, S, 3.534e-7, 1.688e2)
degrade(S, S, 1.433e1)
bindunbind(S, Sinact, 3.534e-7, 1.688e2)
degrade(S, Sinact, 1.433e1)],
"L" => [inactivate(L, 7.810e-3)
bindunbind(L, L, 1.000e-11, 7.440e3)
degrade(L, L, 2.670e2)
bindunbind(L, Linact, 1.000e-11, 7.440e3)
degrade(L, Linact, 2.670e2)],
"K↦E" => [bindunbind(K, E, 9.668e-6,1.000e-2)
degrade(K, E, 1.728e0)],
"K↦G" => [bindunbind(K, G, 2.764e-6, 8.780e-1)
degrade(K, G, 1.502e0)],
"S↦E" => [bindunbind(S, E, 4.197e-7, 1.06e-3)
degrade(S, E, 1.384e4)],
"S↦G" => [bindunbind(S, G, 5.152e-8, 3.894e-3)
degrade(S, G, 8.755e-1)],
"L↦E" => [bindunbind(L, E, 1.977e-8, 1.000e-2)
degrade(L, E, 1.066e2)],
"L↦G" => [bindunbind(L, G, 3.394e-8, 2.365e1)
degrade(L, G, 4.352e0)],
"K↦S" => [bindunbind(K, S, 8.822e-4, 4.114e5)
degrade(K, S, 9.000e-10)
bindunbind(K, Sinact, 8.822e-4, 4.114e5)
degrade(K, Sinact, 9.000e-10)],
"K↦L" => [bindunbind(K, L, 1.756e-4, 3.729e4)
degrade(K, L, 6.505e6)
bindunbind(K, Linact, 1.756e-4, 3.729e4)
degrade(K, Linact, 6.505e6)],
"S↦K" => [bindunbind(S, K, 3.679e-4, 1.562e3)
degrade(S, K, 4.410e2)
bindunbind(S, Kinact, 3.679e-4, 1.562e3)
degrade(S, Kinact, 4.410e2)],
"S↦L" => [bindunbind(S, L, 1.000e-3, 5.000e2)
degrade(S, L, 1.000e-7)
bindunbind(S, Linact, 1.000e-3, 5.000e2)
degrade(S, Linact, 1.000e-7)],
"L↦K" => [bindunbind(L, K, 1.000e-3, 4.118e3)
degrade(L, K, 3.234e1)
bindunbind(L, Kinact, 1.000e-3, 4.118e3)
degrade(L, Kinact, 3.234e1)],
"L↦S" => [bindunbind(L, S, 1.056e-12, 5.000e2)
degrade(L, S, 5.000e-1)
bindunbind(L, Sinact, 1.056e-12, 5.000e2)
degrade(L, Sinact, 5.000e-1)]
);
rxns = Dict(Symbol(k)=>v for (k,v) in rxns)
# define labels to reaction network mappings
functor(x) = oapply(x, Dict(
:catK=>enz(rxns, K),
:catS=>enz(rxns, S),
:catL=>enz(rxns, L),
:catKcatS=>enz_enz(rxns, K,S),
:catKcatL=>enz_enz(rxns, K,L),
:catScatK=>enz_enz(rxns, S,K),
:catScatL=>enz_enz(rxns, S,L),
:catLcatK=>enz_enz(rxns, L,K),
:catLcatS=>enz_enz(rxns, L,S),
:catKsubE=>enz_sub(rxns, K,E),
:catSsubE=>enz_sub(rxns, S,E),
:catLsubE=>enz_sub(rxns, L,E),
:catKsubG=>enz_sub(rxns, K,G),
:catSsubG=>enz_sub(rxns, S,G),
:catLsubG=>enz_sub(rxns, L,G)));
lfunctor(x) = oapply(x, enzyme_generators([:K,:S,:L],[:G,:E,:Spike]))
def_model = apex(functor(enzyme_uwd([:K,:S,:L],[:G,:E])))
def_rates = rates(def_model)
def_concs = Dict(c=>concentrations(def_model)[c] for c in snames(def_model))
def_concs[:Spike] = Spike[2]
def_concs[:Spike_deg] = 0
def_concs[Symbol("K↦Spike")] = 0
def_concs[Symbol("S↦Spike")] = 0
def_concs[Symbol("L↦Spike")] = 0
nothing
end
# ╔═╡ fe9b889d-79c2-493b-9426-e33e6820cd90
md""" Upload a rate data file to use: $(@bind user_csv FilePicker()) """
# ╔═╡ 950d3b4e-f957-45b6-aa80-e3dfc765aad0
md"""Use default rates (override uploaded rates)? $(@bind defbox CheckBox(false))"""
# ╔═╡ 50334069-a50c-467c-94ae-63b9b2264a18
begin
local k_rates, status
try
defbox && error("default rate override")
k_rates = UInt8.(user_csv["data"]) |> IOBuffer |> JSON.parse
status = md"""Using rates from $(user_csv["name"])"""
catch e
k_rates = def_rates
status = md"""No file selected, reverting to default rates"""
end
m_rates = Dict(Symbol(k)=>k_rates[k] for k in keys(k_rates))
valid_enz_sub = Set{Symbol}()
for e in cats
for s in vcat(cats, subs)
if Symbol("bind_$e↦$s") ∈ keys(m_rates)
push!(valid_enz_sub, e)
push!(valid_enz_sub, s)
end
end
end
status
end
# ╔═╡ ddc141ba-d2e8-4ac4-8bc3-12fb1bb9fd4d
md"""
#### Enzyme Diagram
Enzymes
"""
# ╔═╡ 4ad16c5c-73bc-4e42-9bfc-aea73a6bfbfe
begin
#TODO
#Find a more compact way to represent these checkboxes while still dynamically #determining which to display
local boxes = Dict(:K=>md"K $(@bind kbox CheckBox(:K ∈ valid_enz_sub))",
:S=>md"S $(@bind sbox CheckBox(:S ∈ valid_enz_sub))",
:L=>md"L $(@bind Lbox CheckBox(:L ∈ valid_enz_sub && false))")
md"""
$(:K ∈ valid_enz_sub ? boxes[:K] : md"")
$(:S ∈ valid_enz_sub ? boxes[:S] : md"")
$(:L ∈ valid_enz_sub ? boxes[:L] : md"")
"""
end
# ╔═╡ e89794b1-5bcd-4b6c-9cb2-77deca569c2e
md"""Substrates"""
# ╔═╡ dcdb88ef-f04f-4ee8-87cc-bb26f396f064
begin
local boxes = Dict(:G=>md"G $(@bind gbox CheckBox(:G ∈ valid_enz_sub))",
:E=>md"E $(@bind ebox CheckBox(:E ∈ valid_enz_sub && false))",
:Spike=>md"Spike $(@bind pbox CheckBox(:Spike ∈ valid_enz_sub))")
md"""
$(:G ∈ valid_enz_sub ? boxes[:G] : md"")
$(:E ∈ valid_enz_sub ? boxes[:E] : md"")
$(:Spike ∈ valid_enz_sub ? boxes[:Spike] : md"")
"""
end
# ╔═╡ d9f5de8a-f3a2-41c9-9f3c-a0c8347368a4
begin
inp = [kbox, sbox, Lbox];
inpSymb = [:K, :S, :L];
inpF = Symbol[];
for i = 1:3
if inp[i]
push!(inpF,inpSymb[i]);
end
end
outp = [gbox, ebox, pbox];
outSymb = [:G, :E, :Spike];
outF = Symbol[];
for i = 1:3
if outp[i]
push!(outF,outSymb[i]);
end
end
end
# ╔═╡ e6589d31-dce7-42c3-b494-db03fe561ae9
uwd = enzyme_uwd(inpF, outF);
# ╔═╡ 7dbe9349-8b9e-4ac2-b4bf-b59f58a10ebc
begin
display_uwd(uwd)
end
# ╔═╡ cf9e03db-42b7-41f6-80ce-4b12ddb93211
begin
model = uwd |> lfunctor |> apex;
r = join(["'$k': $(m_rates[k])" for k in tnames(model)], ", ");
r2 = join(["'$k': $(def_concs[k])" for k in snames(model)], ", ");
#== Basic Slider Template
<li><input
class='slider'
type='range'
min='-10'
step='0.01'
max='10'
value='0'
oninput='this.nextElementSibling.value=(10**this.value).toExponential(2)'
></input>
<output>1</output></li>
==#
c = vcat(["$(m_rates[k])" for k in tnames(model)], ["$(def_concs[k])" for k in snames(model)]);
form_vals = HTML("""
<bond def = "c">
<form>
<div id ="myDIV" style='height:500px;overflow:scroll'>
<h4>Adjust Rates</h4>
<table>
</table>
</div>
<div id ="concDiv" style='height:500px;overflow:scroll'>
<h4>Adjust Concentrations</h4>
<table id = "table2">
</table>
</div>
<div id ="bindingAff" style='height:500px;overflow:scroll'>
<h4>Binding Affinities</h4>
<table id = "bindingAffTable">
</table>
</div>
</form>
</bond>
<style>
#myDIV {
width: 100%;
padding: 50px 0;
text-align: center;
background-color: #F9F6E5;
margin-top: 20px;
}
#concDiv {
width: 100%;
padding: 50px 0;
text-align: center;
background-color: #F9F6E5;
margin-top: 20px;
display: none
}
#bindingAff {
width: 100%;
padding: 50px 0;
text-align: center;
background-color: #F9F6E5;
margin-top: 20px;
display: none
}
.button {
background-color: #003057;
border: none;
color: white;
padding: 15px 32px;
text-align: center;
text-decoration: none;
display: inline-block;
font-size: 16px;
margin: 4px 2px;
cursor: pointer;
}
.button:focus {
background-color:#BFB37C;
}
.slider {
-webkit-appearance: none;
width: 100%;
height: 7px;
border-radius: 5px;
background: #d3d3d3;
outline: none;
opacity: 0.7;
-webkit-transition: .2s;
transition: opacity .2s;
}
.slider::-webkit-slider-thumb {
-webkit-appearance: none;
appearance: none;
width: 20px;
height: 20px;
border-radius: 50%;
background: #BFB37C;
cursor: pointer;
}
.slider::-moz-range-thumb {
width: 20px;
height: 20px;
border-radius: 50%;
background: #003057;
cursor: pointer;
}
</style>
<script>
//`currentScript` is the current script tag - we use it to select elements//
function hideShowRate() {
var x = document.getElementById("myDIV");
var y = document.getElementById("concDiv");
var z = document.getElementById("bindingAff");
z.style.display = "none";
x.style.display = "block";
y.style.display = "none"
}
function hideShowConc() {
var x = document.getElementById("concDiv");
var y = document.getElementById("myDIV");
var z = document.getElementById("bindingAff");
x.style.display = "block";
y.style.display = "none"
z.style.display = "none"
}
function hideShowBind() {
var x = document.getElementById("bindingAff");
var y = document.getElementById("myDIV");
var z = document.getElementById("concDiv");
x.style.display = "block";
y.style.display = "none"
z.style.display = "none"
generateBindingTable()
}
function returnStrings(s,arr){
let finalArr = []
for (let item in arr){
if(arr[item].includes(s) == true){
finalArr.push(arr[item])
}
}
return finalArr
}
function generateBindingTable(){
let keyNames = Object.keys(rates)
let objVals = Object.values(rates)
let bindArr = []
let unbindArr = []
for (let i in keyNames){
let nm = keyNames[i]
if(nm.substring(0,4) == 'bind'){
bindArr.push(nm)
}else if(nm.substring(0,6) == 'unbind'){
unbindArr.push(nm)
}
}
let kdArr = []; //array of binding affinities
let kdNames = []; // array of binding affinity names
//grab values from sliders
let x = form.getElementsByClassName('sliderval');
let xarr = Array.from(x, (v,_)=>{return v.value})
//Loop over bind and unbind arrays to do calculations
for(let i in keyNames){
if(keyNames[i].substring(0,4) == 'bind'){
let bind = keyNames[i]
for(let j in keyNames){
if(keyNames[j].substring(0,6) == 'unbind'){
let unbind = keyNames[j]
if(bind.substring(5,bind.length) == unbind.substring(7,unbind.length)){
kdArr.push(xarr[j]/xarr[i])
kdNames.push('Kd_'+bind.substring(5,bind.length))
//Create name of deg
let nm = bind.substring(4,bind.length)
let deg_name = 'deg' + nm
for(let k in keyNames){
if(keyNames[k]== deg_name){
let kcat = keyNames[k]
let unbindval = parseFloat(xarr[j]);
let bindval = parseFloat(xarr[i])
let catval = parseFloat(xarr[k])
let k_m = (catval+unbindval)/bindval;
kdArr.push(k_m)
kdNames.push('Km_'+bind.substring(5,bind.length))
kdArr.push(catval/k_m)
kdNames.push('Cat_efficieny_'+bind.substring(5,bind.length))
}
}}}
}
}
}
const list3 = form.querySelector('#bindingAffTable')
while(list3.rows.length > 0) {
list3.deleteRow(0);
}
var header = document.createElement('thead')
var toprow = document.createElement('tr');
var toprowItem = document.createElement('th');
var toprowItem2 = document.createElement('th');
var toprowItem3 = document.createElement('th');
var toprowItem4 = document.createElement('th');
toprowItem.innerText = 'Name';
toprowItem2.innerText = 'Kd';
toprowItem3.innerText = 'Km';
toprowItem4.innerText = 'Catalytic Efficiency';
header.appendChild(toprow)
//toprow.appendChild(header);
toprow.appendChild(toprowItem);
toprow.appendChild(toprowItem2);
toprow.appendChild(toprowItem3);
toprow.appendChild(toprowItem4);
list3.appendChild(toprow);
for (let i = 0; i < kdNames.length/3; i++){
var item = document.createElement('tr');
var label = document.createElement('td');
label.innerText = kdNames[i*3].substring(3)
var label2 = document.createElement('td');
var label3 = document.createElement('td');
var label4 = document.createElement('td');
label2.innerText = kdArr[i*3].toExponential(2)
label3.innerText = kdArr[i*3+1].toExponential(2) // 'placeholder'
label4.innerText = kdArr[i*3+2].toExponential(2) // 'placeholder'
item.appendChild(header)
item.appendChild(label)
item.appendChild(label2)
item.appendChild(label3)
item.appendChild(label4)
list3.appendChild(item)
}
}
const form = currentScript.parentElement.querySelector('form')
const list = form.querySelector('table')
var rates = {$r};
var conc = {$r2};
for ( var r in rates ){
console.log(r);
var item = document.createElement('tr');
var label = document.createElement('th');
label.innerText = r
var slider_box = document.createElement('td');
var slider_val_box = document.createElement('td');
var slider = document.createElement('input');
var slider_val = document.createElement('input');
slider_val.setAttribute('type', 'text');
slider_val.setAttribute('class', 'sliderval');
slider_val.value = rates[r].toExponential(2);
slider.setAttribute('type', 'range');
slider.setAttribute('class', 'slider');
slider.setAttribute('min', '-9.99');
slider.setAttribute('max', '10');
slider.setAttribute('value', '0.0');
slider.setAttribute('step', '0.01');
slider.setAttribute('oninput', `this.parentElement.nextElementSibling.children[0].value=((10**this.value)*\${rates[r]}).toExponential(2)`);
slider_box.appendChild(slider)
slider_val_box.appendChild(slider_val)
item.appendChild(label)
item.appendChild(slider_box)
item.appendChild(slider_val_box)
list.appendChild(item)
}
const list2 = form.querySelector('#table2')
for ( var r in conc ){
console.log(r);
var item = document.createElement('tr');
var label = document.createElement('th');
label.innerText = r
var slider_box = document.createElement('td');
var slider_val_box = document.createElement('td');
var slider = document.createElement('input');
var slider_val = document.createElement('input');
slider_val.setAttribute('type', 'text');
slider_val.setAttribute('class', 'sliderval');
slider_val.value = conc[r].toExponential(2);
slider.setAttribute('type', 'range');
slider.setAttribute('class', 'slider');
slider.setAttribute('min', '-9.99');
slider.setAttribute('max', '10');
slider.setAttribute('value', '0.0');
slider.setAttribute('step', '0.01');
console.log('concentration')
console.log(conc[r]);
let test = conc[r];
if(test == 0){
test = .000001
}
slider.setAttribute('oninput', `this.parentElement.nextElementSibling.children[0].value=((10**this.value)*\${test}).toExponential(2)`);
slider_box.appendChild(slider)
slider_val_box.appendChild(slider_val)
item.appendChild(label)
item.appendChild(slider_box)
item.appendChild(slider_val_box)
list2.appendChild(item)
}
var x = form.getElementsByClassName('sliderval');
function onsubmit(){
// We send the value back to Julia //
form.value = Array.from(x, (v,_)=>{return v.value})
form.dispatchEvent(new CustomEvent('input'))
console.log(form.value)
}
var b = document.createElement('input');
b.setAttribute('type', 'button');
b.setAttribute('class', 'button');
b.value = 'Update Plot';
b.addEventListener('click', function() {onsubmit();console.log('hello from button')})
form.appendChild(b)
onsubmit()
let sp2 = document.getElementById("myDIV")
var d = document.createElement('input')
d.setAttribute('type','button')
d.setAttribute('class','button')
d.value = 'Rates'
d.addEventListener('click', function() {hideShowRate();})
form.insertBefore(d,sp2)
var e = document.createElement('input')
e.setAttribute('type','button')
e.setAttribute('class','button')
e.value = 'Concentrations'
e.addEventListener('click', function() {hideShowConc();})
form.insertBefore(e,sp2)
var f = document.createElement('input')
f.setAttribute('type','button')
f.setAttribute('class','button')
f.value = 'Binding Affinities'
f.addEventListener('click', function() {hideShowBind();})
form.insertBefore(f,sp2)
</script>
""");
end
# ╔═╡ 1f27f695-9d83-4744-b6f0-e3280b746691
length(c)
# ╔═╡ bc90290e-81ba-4963-8a1f-5be15c0f3940
length(tnames(model))
# ╔═╡ 9e847b90-54ae-4afb-bf72-1b9adeb97abc
length(snames(model))
# ╔═╡ 066b7505-e21b-467e-86c1-cea1ff80246e
begin
cur_rate = Dict(tnames(model)[i]=>parse(Float64, c[i]) for i in 1:length(tnames(model)))
# cur_conc = concentrations(model)
cur_conc_prep = Dict(snames(model)[i]=>parse(Float64, c[i+length(tnames(model))]) for i in 1:length(snames(model)))
keysa = keys(cur_conc_prep)
keyArr = Symbol[]
keyArrStr= String[]
valArr = Float64[]
for key in keys(cur_conc_prep)
push!(keyArr,key)
push!(valArr,cur_conc_prep[key])
push!(keyArrStr,String(key))
end
cur_conc = @LArray valArr Tuple(keyArr)
vf = vectorfield(model);
sol = solve(ODEProblem(vf, cur_conc, (0.0,120.0),cur_rate));
nothing
end
# ╔═╡ 3f8db202-ac50-462d-b96d-ba629ca43325
md"""### Iterate over multiple species concentrations $(@bind multCheck CheckBox(false))
#### Select species to iterate:
$(@bind veg Select(keyArrStr))
Starting Concentration: $(@bind initConc TextField()) \
End Concentration: $(@bind endConc TextField()) \
number of steps: $(@bind stepsConc NumberField(1:10, default=5)) \
Choose spacing type: $(@bind spacing Select(["Logarithmic","Linear"])) \
Display combined concentrations excluding degraded? $(@bind combineCheckDeg CheckBox(false)) \
Use constant scale for axis? $(@bind scaleCheck CheckBox(false))
"""
# ╔═╡ cb45ae16-8893-4b80-bae0-fcef646a56b2
begin
if multCheck
keyArr3 = ["A","B"];
graphKeys3 = []
graphKeyVals3 = HTML("""
<bond def = "graphKeys3">
<form>
<div id ="myDIV3" style='height:300px;overflow:scroll'>
<h4>Select Species to plot</h4>
<p>This plot will display how selected species change over iterations. Limit of 6 species. Iteration is indicated by color and species is indicated by marker shape</p>