Merge pull request #779 from LCSB-BioCore/develop

Develop → master merge for 1.5.0

Project.toml

@@ -1,7 +1,7 @@
 name = "COBREXA"
 uuid = "babc4406-5200-4a30-9033-bf5ae714c842"
 authors = ["The developers of COBREXA.jl"]
-version = "1.4.4"
+version = "1.5"
 
 [deps]
 Distributed = "8ba89e20-285c-5b6f-9357-94700520ee1b"

src/analysis/expressions.jl

@@ -0,0 +1,11 @@
+
+"""
+$(TYPEDSIGNATURES)
+
+Build an [`ExpressionLimitedModel`](@ref).
+"""
+make_expression_limited_model(
+    model::MetabolicModel;
+    relative_expression::Dict{String,Float64},
+    bounding_function::Function = expression_probabilistic_bounds,
+) = ExpressionLimitedModel(; relative_expression, bounding_function, inner = model)

src/base/types/wrappers/ExpressionLimitedModel.jl

@@ -0,0 +1,48 @@
+
+"""
+    $(TYPEDEF)
+
+[`ExpressionLimitedModel`](@ref) follows the methodology of the E-Flux algorithm to
+constraint the flux through the reactions in order to simulate the limited
+expression of genes (and thus the limited availability of the gene products).
+
+Use [`make_expression_limited_model`](@ref) or [`with_expression_limits`](@ref)
+to construct the models.
+
+E-Flux algorithm is closer described by: *Colijn, Caroline, Aaron Brandes,
+Jeremy Zucker, Desmond S. Lun, Brian Weiner, Maha R. Farhat, Tan-Yun Cheng, D.
+Branch Moody, Megan Murray, and James E. Galagan. "Interpreting expression data
+with metabolic flux models: predicting Mycobacterium tuberculosis mycolic acid
+production." PLoS computational biology 5, no. 8 (2009): e1000489*.
+
+# Fields
+$(TYPEDFIELDS)
+"""
+Base.@kwdef struct ExpressionLimitedModel <: ModelWrapper
+    """
+    Relative gene expression w.r.t. to some chosen reference; the normalization
+    and scale of the values should match the expectations of the
+    `bounding_function`.
+    """
+    relative_expression::Dict{String,Float64}
+
+    "The wrapped model."
+    inner::MetabolicModel
+
+    """
+    Function used to calculate the new reaction bounds from expression.
+    In [`make_expression_limited_model`](@ref) this defaults to
+    [`expression_probabilistic_bounds`](@ref).
+    """
+    bounding_function::Function
+end
+
+COBREXA.unwrap_model(m::ExpressionLimitedModel) = m.inner
+
+function COBREXA.bounds(m::ExpressionLimitedModel)::Tuple{Vector{Float64},Vector{Float64}}
+    (lbs, ubs) = bounds(m.inner)
+    lims = collect(
+        m.bounding_function(m.relative_expression, reaction_gene_association(m.inner, rid)) for rid in reactions(m.inner)
+    )
+    (lbs .* lims, ubs .* lims)
+end

src/base/utils/eflux.jl

@@ -0,0 +1,16 @@
+
+"""
+$(TYPEDSIGNATURES)
+
+Create E-Flux-like bounds for a reaction that requires gene products given by
+`grr`, with expression "choke" data given by relative probabilities (between 0
+and 1) in `relative_expression`.
+"""
+function expression_probabilistic_bounds(
+    relative_expression::Dict{String,Float64},
+    grr::Maybe{Vector{Vector{String}}},
+)::Float64
+    isnothing(grr) && return 1.0
+    lup(g) = get(relative_expression, g, 1.0)
+    1 - prod(1 - prod(lup.(gr)) for gr in grr)
+end

src/reconstruction/expressions.jl

@@ -0,0 +1,10 @@
+"""
+$(TYPEDSIGNATURES)
+
+Specifies a model variant which adds extra semantics of the
+[`ExpressionLimitedModel`](@ref), simulating the E-Flux algorithm. The
+arguments are forwarded to [`make_expression_limited_model`](@ref). Intended
+for usage with [`screen`](@ref).
+"""
+with_expression_limits(; kwargs...) =
+    model -> make_expression_limited_model(model; kwargs...)

test/analysis/expressions.jl

@@ -0,0 +1,16 @@
+
+@testset "Expression-limited models" begin
+    orig_model = load_model(model_paths["e_coli_core.json"])
+
+    model =
+        orig_model |>
+        with_expression_limits(relative_expression = Dict(genes(orig_model) .=> 0.5))
+
+    bs = Dict(reactions(model) .=> bounds(model)[1])
+
+    @test getindex.(Ref(bs), ["PFK", "ENO", "ACALD"]) == [0, -500, -750]
+
+    fluxes = flux_balance_analysis_dict(model, Tulip.Optimizer)
+
+    @test isapprox(fluxes["BIOMASS_Ecoli_core_w_GAM"], 0.21386, atol = TEST_TOLERANCE)
+end