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Update code to match preprint v2 #2

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d0c22eb
Update code to match preprint v2
bbantal Jun 24, 2026
84ebc47
Update solver dependency to OrdinaryDiffEqTsit5
bbantal Jun 24, 2026
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129 changes: 70 additions & 59 deletions GUI/backend/src/NTModelModule.jl
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Original file line number Diff line number Diff line change
Expand Up @@ -19,21 +19,23 @@ mutable struct NTModel
ps_units::Dict{Symbol, String}
u0_desc::Dict{Symbol, String}
ps_desc::Dict{Symbol, String}


# Parameters
# ----------
function NTModel()

# Initial conditions
u0 = Dict([
:GLN_e => 0.28, # mM
:GLN_i => 0.07, # mM
:GLU_e => 10.0, # mM
:GLU_i => 0.06, # mM
:GABA_i => 0.6, # mM
:GABA_v => 0.06, # mM
:GLU_i => 0.13, # mM
:GABA_i => 0.73, # mM
:GABA_v => 0.1, # mM
:GLN_a => 3.8, # mM
:GLU_a => 0.8, # mM
:KET_b => 0.0, # mM
])
]); # [X] = mM

# Units for initial conditions
u0_units = Dict([
Expand All @@ -46,7 +48,7 @@ mutable struct NTModel
:GLN_a => "mM",
:GLU_a => "mM",
:KET_b => "mM",
])
]);

u0_desc = Dict([
:GLN_e => "Glutamine in excitatory neurons",
Expand All @@ -58,29 +60,32 @@ mutable struct NTModel
:GLN_a => "Glutamine in astrocytes",
:GLU_a => "Glutamate in astrocytes",
:KET_b => "Brain ketone concentration",
])
]);

# Parameters
ps = Dict([
# Neurotransmitter cycling
# Neurotranstmitter cycling
:c_vpmas => 1.0,
:k_syn_e => 0.01912,
:k_syn_i => 0.79882,
:Vmax_GAD67 => 0.20769,
:KM_GAD67 => 0.2,
:Vmax_GT => 0.05860,
:KM_GT => 0.13359,
:Vmax_GAD65 => 0.05591,
:k_syn_e => 0.0191,
:k_syn_i => 0.4793,
:Vmax_GAD67 => 0.0959,
:KM_GAD67 => 0.13,
:Vmax_GT => 0.0582,
:KM_GT => 0.1563,
:Vmax_GAD65 => 0.0516,
:KM_GAD65 => 0.01,
:Vmax_GDH => 0.096,
:KM_GDH => 0.8,
:h_GDH => 4.0,
:Vmax_GS => 0.753,
:KM_GS => 0.8,
:KI_GS => 3.8,
:h_GS => 4.0,
:Vmax_GDH => 0.0764,
:KM_GDH => 0.8,
:h_GDH => 4.0,
:k_ox => 0.2,
:V_out => 0.012,
:V_anapl => 0.06,
:GLN_p => 0.5,
:GLN_ratio => 1/8,
:V_out0 => 0.012,
:Tmax_gln => 0.018,
:KT_gln => 0.25,

# Energy metabolism
:V_ATP => 11.94, # mM/min
Expand All @@ -92,29 +97,32 @@ mutable struct NTModel
:k_ket => 0.162, # 1/min
:ATPket => 21.5,
:KET_p => 0,
])
]);# [V] = mM/min, [KM] = mM, [X] = mM

# Units for parameters
ps_units = Dict([
# Neurotransmitter cycling
# Neurotranstmitter cycling
:c_vpmas => "-",
:k_syn_e => "1/min",
:k_syn_i => "1/min",
:k_syn_i => "1/min",
:Vmax_GAD67 => "mM/min",
:KM_GAD67 => "mM",
:Vmax_GT => "mM/min",
:KM_GT => "mM",
:Vmax_GAD65 => "mM/min",
:KM_GAD65 => "mM",
:Vmax_GS => "mM/min",
:KM_GS => "mM",
:KI_GS => "mM",
:h_GS => "-",
:Vmax_GDH => "mM/min",
:KM_GDH => "mM",
:h_GDH => "-",
:k_ox => "-",
:V_out => "mM/min",
:Vmax_GS => "mM/min",
:KM_GS => "mM",
:KI_GS => "mM",
:V_anapl => "mM/min",
:GLN_p => "mM",
:GLN_ratio => "-",
:V_out0 => "mM/min",
:Tmax_gln => "mM/min",
:KT_gln => "mM",

# Energy metabolism
:V_ATP => "mM/min",
Expand All @@ -126,28 +134,32 @@ mutable struct NTModel
:k_ket => "1/min",
:ATPket => "-",
:KET_p => "mM",
])

]);

ps_desc = Dict([
# Neurotransmitter cycling
# Neurotranstmitter cycling
:c_vpmas => "relative rate of PMAS",
:k_syn_e => "rate constant for glutamate vesicle loading",
:k_syn_i => "rate constant for GABA vesicle loading",
:k_syn_i => "rate constant for GABA vesicle loading",
:Vmax_GAD67 => "GAD67 maximum rate",
:KM_GAD67 => "GAD67 Michaelis-Menten constant for glutamate",
:Vmax_GT => "GT maximum rate",
:KM_GT => "GT Michaelis-Menten constant for GABA",
:Vmax_GAD65 => "GAD65 maximum rate",
:KM_GAD65 => "GAD65 Michaelis-Menten constant for glutamate",
:Vmax_GDH => "GDH maximum rate",
:KM_GDH => "GDH Michaelis–Menten constant for glutamate",
:h_GDH => "GDH Hill exponent",
:Vmax_GS => "GS maximum rate",
:KM_GS => "GS Michaelis-Menten constant for glutamate",
:KI_GS => "GS inhibition constant for glutamine",
:h_GS => "GS Hill exponent for the inhibition by GLN",
:Vmax_GDH => "GDH maximum rate",
:KM_GDH => "GDH Michaelis-Menten constant for glutamate",
:h_GDH => "GDH Hill exponent",
:k_ox => "relative portion of glutamate oxidation",
:V_out => "rate of GLN efflux",
:V_anapl => "rate of anaplerotic flux",
:GLN_p => "plasma glutamine concentration",
:GLN_ratio => "ratio of extracellular vs. intracellular glutamine",
:V_out0 => "baseline rate of glutamine efflux",
:Tmax_gln => "glutamine transport maximum rate",
:KT_gln => "glutamine transport Michaelis-Menten constant",

# Energy metabolism
:V_ATP => "rate of ATP synthesis",
Expand All @@ -159,45 +171,44 @@ mutable struct NTModel
:k_ket => "Ketone utilization rate constant",
:ATPket => "ATP yield from ketones",
:KET_p => "Plasma Ketone concentration",
])
]);

# Model definition
# -------------

# Custom rate functions
mm_reversible(S1P, S1B, Vmax, Km1) =
Vmax / Km1 * (S1P - S1B) / (1 + S1P/Km1 + S1B/Km1)
mm_reversible(S1P, S1B, Vmax, Km) = Vmax * (S1P - S1B) / (Km + S1P + S1B);
CMRglc(V_ATP, KET_b, k_ket, ATPglc, ATPket) = ((V_ATP - ATPket*KET_b*k_ket)/ATPglc)/0.91
Vpmas_e(cmrglc, c_vpmas) = c_vpmas*(cmrglc*0.91*0.75*0.83 - 0.077)/0.812
Vpmas_i(cmrglc, c_vpmas) = c_vpmas*(cmrglc*0.91*0.75*0.17 - 0.011)/0.763

Vpmas_e(cmrglc) = (cmrglc*0.91*0.75*0.83 - 0.077)/0.812;
Vpmas_i(cmrglc) = (cmrglc*0.91*0.75*0.17 - 0.011)/0.763;
# Reaction network
model = @reaction_network begin

# Ketone transport
# Ketone metabolism
mm_reversible(KET_p, KET_b, Tmax_ket, KT_ket), 0 => KET_b, [description="Ketone transport"]

# Ketone utilization
k_ket*KET_b, KET_b => 0, [description="Ketone utilization"]

# Glutamatergic neuron
Vpmas_e(CMRglc(V_ATP, KET_b, k_ket, ATPglc, ATPket), c_vpmas), GLN_e => GLU_e, [description="PMAS in e"]
k_syn_e * GLU_e, GLU_e => GLU_a, [description="GLU cycling"]
Vpmas_e(CMRglc(V_ATP, KET_b, k_ket, ATPglc, ATPket))*c_vpmas, GLN_e => GLU_e, [description="PMAS in e"]
k_syn_e * GLU_e, GLU_e => GLU_a, [description="GLU synaptic flux"]

# GABAergic neuron
Vpmas_i(CMRglc(V_ATP, KET_b, k_ket, ATPglc, ATPket), c_vpmas), GLN_i => GLU_i, [description="PMAS in i"]
Vpmas_i(CMRglc(V_ATP, KET_b, k_ket, ATPglc, ATPket))*c_vpmas, GLN_i => GLU_i, [description="PMAS in i"]
mm(GLU_i, Vmax_GAD67, KM_GAD67), GLU_i => GABA_i, [description="GAD67"]
mm(GLU_i, Vmax_GAD65, KM_GAD65), GLU_i => GABA_v, [description="GAD65"]
mm(GABA_i, Vmax_GT, KM_GT), GABA_i => GLU_i, [description="GT"]
k_syn_i * GABA_v, GABA_v => GLU_a, [description="GABA cycling"]
k_syn_i * GABA_v, GABA_v => GLU_a, [description="GABA synaptic flux"]

# Astrocyte
k_ox * k_syn_e * GLU_e + V_out, 0 => GLU_a, [description="Anaplerosis"]
V_anapl, 0 => GLU_a, [description="Anaplerosis"]
Vmax_GDH * (GLU_a/KM_GDH)^h_GDH / (1 + (GLU_a/KM_GDH)^h_GDH), GLU_a => 0, [description="GDH"]
Vmax_GS * GLU_a / (KM_GS*(1 + (GLN_a/KI_GS)^h_GS) + GLU_a), GLU_a => GLN_a, [description="GS"]
Vpmas_e(CMRglc(V_ATP, KET_b, k_ket, ATPglc, ATPket), c_vpmas), GLN_a => GLN_e, [description="GLN uptake in e"]
Vpmas_i(CMRglc(V_ATP, KET_b, k_ket, ATPglc, ATPket), c_vpmas), GLN_a => GLN_i, [description="GLN uptake in i"]
V_out, GLN_a => 0, [description="GLN efflux"]
Vmax_GS * GLU_a / (KM_GS*(1 + GLN_a/KI_GS) + GLU_a), GLU_a => GLN_a, [description="GS"]
Vpmas_e(CMRglc(V_ATP, KET_b, k_ket, ATPglc, ATPket))*c_vpmas, GLN_a => GLN_e, [description="GLN uptake in e"]
Vpmas_i(CMRglc(V_ATP, KET_b, k_ket, ATPglc, ATPket))*c_vpmas, GLN_a => GLN_i, [description="GLN uptake in i"]
V_out0 + mm_reversible(GLN_a*GLN_ratio, GLN_p, Tmax_gln, KT_gln), GLN_a => 0, [description="GLN efflux"]

end
end;

return new(model, u0, ps, nothing, u0_units, ps_units, u0_desc, ps_desc)

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