Merge pull request #2 from NTUMitoLab/update20211018

update

ExpressionLevel.ipynb

@@ -147,7 +147,7 @@
  ],
  "metadata": {
   "kernelspec": {
-   "display_name": "Julia 1.6.1",
+   "display_name": "Julia 1.6.2",
    "language": "julia",
    "name": "julia-1.6"
   },

ExpressionLevelEffect.ipynb

@@ -0,0 +1,211 @@
+{
+ "cells": [
+  {
+   "cell_type": "code",
+   "execution_count": null,
+   "id": "0db6e64e-de69-4738-89a6-a987e3749be8",
+   "metadata": {},
+   "outputs": [],
+   "source": [
+    "using Pkg"
+   ]
+  },
+  {
+   "cell_type": "code",
+   "execution_count": null,
+   "id": "3dc2fbee-8dc0-4ffe-a17a-43d87578507a",
+   "metadata": {},
+   "outputs": [],
+   "source": [
+    "Pkg.activate(\"ExpressionLevelEffect\")"
+   ]
+  },
+  {
+   "cell_type": "code",
+   "execution_count": null,
+   "id": "b69ddf39-bdf0-44cb-922e-734a44f23dc8",
+   "metadata": {},
+   "outputs": [],
+   "source": [
+    "@time Pkg.instantiate()"
+   ]
+  },
+  {
+   "cell_type": "code",
+   "execution_count": null,
+   "id": "0137d189-11ce-4172-903f-4aa446c78171",
+   "metadata": {},
+   "outputs": [],
+   "source": [
+    "using Revise, FrequencyResponse, DifferentialEquations, LabelledArrays, Plots, ProgressMeter, Distributed\n",
+    "import RetroSignalModel as rs"
+   ]
+  },
+  {
+   "cell_type": "code",
+   "execution_count": null,
+   "id": "fb35f107-6c3c-4913-ba68-506a66e07eea",
+   "metadata": {},
+   "outputs": [],
+   "source": [
+    "include(\"ExpressionLevelEffect/script/utils.jl\")"
+   ]
+  },
+  {
+   "cell_type": "code",
+   "execution_count": null,
+   "id": "2acf00dc-b69f-49b9-836b-cbf542382d1a",
+   "metadata": {},
+   "outputs": [],
+   "source": [
+    "# Load librarys to workers\n",
+    "#addprocs(length(Sys.cpu_info()) - nprocs() - 1, exeflags=\"--project=$(Base.active_project())\")\n",
+    "#@everywhere begin \n",
+    "    using Revise, FrequencyResponse, DifferentialEquations, LabelledArrays, Plots, ProgressMeter\n",
+    "    import RetroSignalModel as rs\n",
+    "#end\n",
+    "\n",
+    "#@everywhere begin \n",
+    "\n",
+    "\n",
+    "    # Load Model \n",
+    "    i_sol_PLACE_HOLDER=1\n",
+    "    RTGm = rs.rtgM4(i_sol_PLACE_HOLDER)\n",
+    "    param= (; u=RTGm.u, p=RTGm.p);\n",
+    "\n",
+    "    # Dynamical Signal\n",
+    "    dynmodel = DynModel(\n",
+    "    model = RTGm.model,\n",
+    "    u = param.u,\n",
+    "    p = param.p,\n",
+    "    solver= Rosenbrock23(),\n",
+    "    signal_func = PosSine(ω=0.05,θ=(3/2)*π, amp=1),\n",
+    "    input_i = 1,\n",
+    "    tspan=(0.,500.),\n",
+    "    init_ss = true # Get steady state\n",
+    "    );\n",
+    "\n",
+    "    sol = solve(dynmodel;tmax=1.);\n",
+    "\n",
+    "\n",
+    "    function sim_square(RTGm, levels)\n",
+    "        dynmodel = DynModel(\n",
+    "            model = RTGm.model,\n",
+    "            u = rs.init_u(RTGm; expLevels=levels),\n",
+    "            p = RTGm.p,\n",
+    "            solver= Rosenbrock23(),\n",
+    "            signal_func= SquarePulse(\n",
+    "                                            t_str = 125.,\n",
+    "                                            t_end = 375,\n",
+    "                                            amp_l =0.,\n",
+    "                                            amp_h = 1.),\n",
+    "            input_i = 1,\n",
+    "            tspan=(0.,500.),\n",
+    "            init_ss = true # Get steady state\n",
+    "        );\n",
+    "        sol = solve(dynmodel;tmax=1.);\n",
+    "        return sol\n",
+    "    end\n",
+    "\n",
+    "    function mut_tuple(tup, i, mul)\n",
+    "        vs = NamedTuple{tuple(i)}(tuple(tup[i]*mul))\n",
+    "        return LVector(merge(tup, vs))\n",
+    "    end\n",
+    "\n",
+    "    \"\"\"\n",
+    "    pr: protein to change\n",
+    "    ch: change fold\n",
+    "    obs: observe protein\n",
+    "    \"\"\"\n",
+    "    function ch_cmp(pr, ch, obs;i = i_sol_PLACE_HOLDER)\n",
+    "        RTGm = rs.rtgM4(i)\n",
+    "        levels =rs.getExpLevels(;condition=rs.DefaultCondition)\n",
+    "\n",
+    "        #simulation\n",
+    "        sol = sim_square(RTGm, levels)\n",
+    "        sol2 = sim_square(RTGm, mut_tuple(levels, pr, ch)) \n",
+    "\n",
+    "\n",
+    "        p = Plots.plot(sol.t,total_conc(sol, RTGm, obs), label=\"Control\")\n",
+    "        Plots.plot!(p, sol2.t,total_conc(sol2, RTGm, obs), label=string(pr,\":\",ch,\"x\"))\n",
+    "\n",
+    "        Plots.xlabel!(p, \"time\")\n",
+    "        Plots.ylabel!(p, \"Concentration ($(obs))\")\n",
+    "        return p\n",
+    "    end\n",
+    "\n",
+    "    function ch_cmp!(p, pr, ch, obs;i = i_sol_PLACE_HOLDER, plot_control=false)\n",
+    "        RTGm = rs.rtgM4(i)\n",
+    "        levels =rs.getExpLevels(;condition=rs.DefaultCondition)\n",
+    "\n",
+    "        #simulation\n",
+    "        sol2 = sim_square(RTGm, mut_tuple(levels, pr, ch)) \n",
+    "\n",
+    "\n",
+    "        if plot_control \n",
+    "            sol = sim_square(RTGm, levels)\n",
+    "            Plots.plot!(p, sol.t,total_conc(sol, RTGm, obs), label=\"Control\") \n",
+    "        end\n",
+    "\n",
+    "        Plots.plot!(p, sol2.t,total_conc(sol2, RTGm, obs), label=string(pr,\":\",ch,\"x\"))\n",
+    "\n",
+    "        Plots.xlabel!(p, \"time\")\n",
+    "        Plots.ylabel!(p, \"Concentration ($(obs))\")\n",
+    "        return p\n",
+    "    end\n",
+    "\n",
+    "    \"\"\"\n",
+    "    ob: name of observe protein; chs: list of changes\n",
+    "    \"\"\"\n",
+    "    function simulation(ob, pr, chs)\n",
+    "        plot_control = false\n",
+    "        p_ = Plots.plot()\n",
+    "        for c in chs \n",
+    "            if plot_control == false \n",
+    "                ch_cmp!(p_, pr, c, ob;plot_control=true)\n",
+    "                plot_control = true\n",
+    "            end\n",
+    "            ch_cmp!(p_, pr, c, ob;plot_control=false) \n",
+    "        end\n",
+    "        name = string(pr,\"_\",\"foldChange\" ,\"_\",\"obs_\",ob)\n",
+    "        @show name\n",
+    "        Plots.savefig(p_, joinpath(dirname(@__DIR__),\"result\",\"$(name).pdf\"))\n",
+    "        p_ = nothing\n",
+    "    end\n",
+    "#end \n",
+    "\n",
+    "levels =rs.getExpLevels(;condition=rs.DefaultCondition)\n",
+    "prs = keys(levels)\n",
+    "obs = [:Rtg1_n, :Rtg3_n]\n",
+    "chs = [0.001,0.01,0.1,0.2,0.5,1.,2.,4. ,8., 16.,50.,100.]\n",
+    "\n",
+    "sims = [(b,pr,chs)  for b in obs for pr in prs]\n",
+    "\n",
+    "#@showprogress map(x->simulation(x...), sims)\n",
+    "@showprogress for sim in sims \n",
+    "    simulation(sim...)\n",
+    "end"
+   ]
+  },
+  {
+   "cell_type": "code",
+   "execution_count": null,
+   "id": "1164fbba-b9a8-4f92-a5fa-b481962f885f",
+   "metadata": {},
+   "outputs": [],
+   "source": []
+  }
+ ],
+ "metadata": {
+  "kernelspec": {
+   "display_name": "Julia 1.6.2",
+   "language": "julia",
+   "name": "julia-1.6"
+  },
+  "language_info": {
+   "name": ""
+  }
+ },
+ "nbformat": 4,
+ "nbformat_minor": 5
+}

PlottingMakie/Project.toml → ExpressionLevelEffect/Project.toml

@@ -4,9 +4,13 @@ authors = ["stevengogogo <stevengogogo4321@gmail.com>"]
 version = "0.1.0"
 
 [deps]
+Catalyst = "479239e8-5488-4da2-87a7-35f2df7eef83"
+Dierckx = "39dd38d3-220a-591b-8e3c-4c3a8c710a94"
 DifferentialEquations = "0c46a032-eb83-5123-abaf-570d42b7fbaa"
 FrequencyResponse = "23be90ff-b906-42a4-9508-8c19908ecbef"
+Interpolations = "a98d9a8b-a2ab-59e6-89dd-64a1c18fca59"
 LabelledArrays = "2ee39098-c373-598a-b85f-a56591580800"
+Optim = "429524aa-4258-5aef-a3af-852621145aeb"
 Plots = "91a5bcdd-55d7-5caf-9e0b-520d859cae80"
 ProgressMeter = "92933f4c-e287-5a05-a399-4b506db050ca"
 PyPlot = "d330b81b-6aea-500a-939a-2ce795aea3ee"

ExpressionLevelEffect/script/analytic_Rtg2.jl

@@ -0,0 +1,59 @@
+
+using Pkg
+Pkg.activate(dirname(@__DIR__))
+Pkg.instantiate()
+
+using Catalyst
+import RetroSignalModel as rs
+
+function get_total_conc(concs, feature)
+    Is = [ i for i in keys(RTGm.u) if occursin(feature,string(i))]
+    return sum(concs[Is])
+end
+
+rtg2m = @reaction_network begin 
+    (1), s→s
+    (hill(s, ksV, ksD, n_s), k2I), Rtg2_ina_c ↔ Rtg2_act_c #[1]
+    (k2M, kn2M), Rtg2_act_c + Mks ↔ Rtg2Mks_c
+    (kBM, knBM), Bmh + Mks ↔ BmhMks
+end n_s ksV ksD k2I k2M kn2M kBM knBM
+
+
+RTGm = rs.rtgM4(1)
+Catalyst.params(RTGm.model)
+Catalyst.params(rtg2m)
+
+ps = NamedTuple{tuple(Symbol.(params(RTGm.model))...)}(RTGm.p)
+psR = NamedTuple{tuple(Symbol.(params(rtg2m))...)}(tuple([getindex(ps, Symbol(i)) for i in Catalyst.params(rtg2m)]...))
+
+
+
+
+Kr = psR.kn2M/psR.k2M 
+Kb = psR.knBM/psR.kBM 
+Kt(s) = psR.k2I/ (psR.ksV * s^psR.n_s / (psR.ksD^psR.n_s + s^psR.n_s))
+Kr_(s) = Kr*(1+1/Kt(s))
+
+
+Rtg2₀ = get_total_conc(RTGm.u, "Rtg2")
+Bmh₀ = get_total_conc(RTGm.u, "Bmh")
+Mks₀ = get_total_conc(RTGm.u, "Mks")
+
+a(s) = Kr_(s) + Kb + Rtg2₀ + Bmh₀ - Mks₀
+b(s) = Kb*(Rtg2₀ - Mks₀) + Kr_(s)*(Bmh₀ - Mks₀)+Kr_(s)*Kb 
+c(s) = -Kr_(s)*Kb*Mks₀
+
+θ(s) = acos( (-2*a(s)^3 + 9*a(s)*b(s) - 27*c(s)) / (2*sqrt((a(s)^2-3*b(s))^3)))
+
+Mks(s) = -a(s)/3 + 2/3*sqrt(a(s)^2 - 3*b(s)) * cos(θ(s)/3)
+
+function auxB(s)
+    2*sqrt(a(s)^2-3*b(s))*cos(θ(s)/3) - a(s)
+end
+function BmhMks(s) 
+    return Bmh₀*aux(s) / (3*Kb + aux(s))
+end
+
+Mks(1)
+BmhMks(0.)
+BmhMks(0.01)