cell_cycle 0.0.2

data/test/virginia_test.rb

@@ -0,0 +1,270 @@
+#! /usr/bin/ruby
+# encoding: utf-8
+
+require 'minitest/autorun'
+require 'sy'
+require 'y_nelson' and include YNelson
+
+bp = './../../lib/'
+  .tap { |s| s.singleton_class.class_exec do attr_accessor :loaded end }
+  .tap { |s| s.loaded = {} }
+
+require_once = -> path do
+  bp.loaded[ path ] or
+    require( bp + path ) && bp.loaded.update( path => true )
+end
+
+describe :mammalian_cell_cycle do
+  before do
+    require_once.( 'ttp_pathway/version' )
+    require_once.( 'michaelis_menten' )
+    require_once.( 'general_assumptions' )
+    require_once.( 'cell_cycle/virginia' )
+  end
+
+  describe "sanity of this test itself" do
+    it "should have version loaded" do
+      TtpPathway::VERSION.must_be_kind_of String
+    end
+
+    it "should have michaelis_menten loaded" do
+      [ Vmax, Km_reduced, Occupancy, MMi ].all? &[ :kind_of?, Proc ]
+    end
+
+    it "should have general_assumptions loaded" do
+      assert defined? Cell_diameter
+      assert defined? Cytoplasm_volume
+      assert defined? Pieces_per_µM
+    end
+  end
+
+  describe "basic elements" do
+    it "should have basic interface places" do
+      A_phase.must_be_kind_of Place
+      S_phase.must_be_kind_of Place
+      Cdc20A.must_be_kind_of Place
+    end
+
+    it "should have parametrizing constants CASE and G2_MODULE" do
+      assert defined? CASE
+      assert defined? G2_MODULE
+    end
+
+    it "should have Godlbeter-Koshland function defined" do
+      assert B.is_a? Proc     # B function as per Csikasznagy2006agm
+      assert GK.is_a? Proc    # Golbeter-Koshland function
+    end
+
+    it "should have growth and cell division related constants" do
+      assert defined? CELL_MASS_DOUBLING_TIME
+      assert defined? CELL_GROWTH_RATE
+      assert defined? CycB_DIVISION_THRESHOLD
+    end
+
+    it "should have DATA hash holding the generic cycle parameters for " +
+      "budding yeast (BY), mammalian cell (MA), fission yeast (FY), and " +
+      "Xenopus embryo (XE)" do
+      key, val = DATA.first
+      key.must_be_kind_of Symbol
+      val.must_be_kind_of Hash
+      val.keys.must_equal [ :BY, :MA, :FY, :G2, :XE ]
+      # Now we will make an example of a single parameter that must be present
+      # both as a key in the DATA hash, and as a constant in the TOP namespace.
+      DATA.keys.must_include :J20
+      assert defined? J20                # Must be also defined as a constant.
+      J20.must_equal DATA[ :J20 ][ :MA ] # It must be set to the mammalian parameter.
+    end
+  end
+
+  describe "Module 0 -- cell growth and division" do
+    describe "places" do
+      it "should have Mass (cell mass) place" do Mass.must_be_kind_of Place end
+      it "should have CycD (cyclin D) place" do CycD.must_be_kind_of Place end
+    end
+
+    describe "assignment transitions" do
+      describe "A transition controlling CycD" do
+        it "must exist" do
+          assert transition( :CycD_ϝ ).A? # it must exist and be an A transition
+        end
+
+        describe "its dynamic behavior" do
+          before do
+            @net = Net() << Mass << CycD << transition( :CycD_ϝ )
+            @sim = @net.simulation initial_marking: { Mass: 1.0 }
+            @feature = @net.State.Feature.Assignment( CycD )
+          end
+
+          it "must assign to CycD a value proportional to the cell mass" do
+            v1 = @feature.extract_from( @sim )
+            # construct a second simulation with double mass:
+            sim2 = @net.simulation initial_marking: { Mass: 2.0 }
+            v2 = @feature.extract_from( sim2 )
+            # with double mass, the action of CycD_ϝ should be double
+            v2.must_be_within_epsilon v1 * 2
+          end
+        end
+      end
+    end
+
+    describe "transitions" do
+      describe "Cell_growth" do
+        it "should be of correct type" do
+          assert Cell_growth.TS?
+        end
+
+        describe "its dynamic behavior" do
+          before do
+            @net = Net() << Mass << Cell_growth
+            @sim = @net.simulation initial_marking: { Mass: 1.0 }, step: 0.1
+          end
+
+          it "should define exponential growth" do
+            # Starting mass is 1. After 10 time units, the mas will be:
+            @sim.run! upto: 10
+            mass_after_10 = @sim.marking( :Mass ).first
+            # After 20 time units, the mass should be the square of it:
+            @sim.run! upto: 20
+            mass_after_20 = @sim.marking( :Mass ).first
+            mass_after_20.must_be_within_epsilon( mass_after_10 ** 2 )
+          end
+        end
+      end
+
+      describe "Cytokinesis && License_cocking" do
+        it "should be of correct type" do
+          assert Cytokinesis.A?
+          assert License_cocking.A?
+        end
+
+        describe "dynamic behavior" do
+          before do
+            @net = Net() << Mass << ActCycB << Ck_license << Cytokinesis << License_cocking
+          end
+
+          describe "low cyclin B, cytokinesis license present" do
+            before do
+              @s1 = @net.simulation initial_marking: { Ck_license: 1, Mass: 1.0, ActCycB: 0.01 }, step: 1.0
+              @s1.step!
+            end
+
+            it "cytokinesis should happen" do
+              @s1.m( Ck_license ).first.must_equal 0     # consumed
+              assert @s1.m( Mass ).first < 1             # decreased
+            end
+          end
+
+          describe "high cyclin B, cytokinesis license absent" do
+            before do
+              @s2 = @net.simulation initial_marking: { Ck_license: 0, Mass: 1.0, ActCycB: 100 }, step: 1.0
+              @s2.step!
+            end
+
+            it "license should cock" do
+              @s2.m( Ck_license ).first.must_equal 1     # cocked
+              assert @s2.m( Mass ).first >= 1            # not decreased
+            end
+          end
+
+          describe "high cyclin B, cytokinesis license present" do
+            before do
+              @s3 = @net.simulation initial_marking: { Ck_license: 1, Mass: 1.0, ActCycB: 100 }, step: 1.0
+              @s3.step!
+            end
+
+            it "cytokinesis should not happen" do
+              @s3.m( Ck_license ).first.must_equal 1     # unchanged
+              assert @s3.m( Mass ).first >= 1            # not decreased
+            end
+          end
+
+          describe "low cyclin B, cytokinesis license absent" do
+            before do
+              @s4 = @net.simulation initial_marking: { Ck_license: 0, Mass: 1.0, ActCycB: 0.1 }, step: 1.0
+              @s4.step!
+            end
+
+            it "nothing should happen" do
+              @s4.m( Ck_license ).first.must_equal 0     # cocked
+              assert @s4.m( Mass ).first >= 1            # not decreased
+            end
+          end
+        end
+      end
+    end
+  end
+
+  describe "Modules 4, 10, and 13 -- synthesis and degradation of cyclins B, E, and A" do
+    # Cyclin E is active primarily at the G1-S boundary, cyclin A is active from S phase
+    # to early M phase, and cyclin B is essential for mitosis.
+
+    it "must have certain places" do
+      CycB.must_be_kind_of Place      # Mitotic Cdk/cyclin complex
+      ActCycB.must_be_kind_of Place   # activated CycB
+      CycE.must_be_kind_of Place      # G1/S transition inducer Cdk/cyclin
+      ActCycE.must_be_kind_of Place   # activated CycE
+      CycA.must_be_kind_of Place      # S-phase Cdk/cyclin complex
+      ActCycA.must_be_kind_of Place   # S-phase Cdk/cyclin complex
+    end
+
+    describe "assigment transitions" do
+      
+    end
+
+    describe "transitions" do
+      
+    end
+  end
+
+  describe "Modules 1 and 2 -- regulation of the anaphase promoting complex (APC)" do
+    # The APC works in conjunction with Cdc20 and Cdh1 to ubiquitinylate
+    # cyclin B, thereby labeling it for degradation by proteasomes. The APC
+    # must be phosphorylated by the mitotic CycB kinase before it will associate
+    # readily with Cdc20, but not so with Cdh1. On the other hand, Cdh1 can be
+    # inactivated by phosphorylation by cyclin-dependent kinases. Cdc14 is a
+    # phosphatase that opposes Cdk by dephosphorylating and activating Cdh1.
+
+    describe "places" do
+      
+    end
+
+    describe "transitions" do
+      
+    end
+  end
+
+  describe "Module 8 -- synthesis and degradation of CKI (cyclin-dependent kinase inhibitor)" do
+    # Degradation of CKI is promoted by phoshporylation by cyclin-dependent kinases and
+    # inhibited by Cdc14 phosphatase.
+
+    describe "places" do
+      
+    end
+  end
+
+  describe "Modules 6, 9 and 12 -- reversible binding of CKI to cyclin/Cdk dimers to produce " +
+    "catalytically inactive trimers (stoichiometric inhibition)." do
+    
+  end
+
+  describe "Module 3, 7, and 11 -- regulation of the transcription factors that drive " +
+    "expression of cyclins and CKI" do
+    # TFB is activated by cyclin B-dependent kinase. TFE is activated by some cyclin-dependent
+    # kinases and inhibited by others. TFI is inhibited by cyclin B-dependent kinase and activated
+    # by Cdc14 phosphatase.
+  end
+
+  describe "Module 5 -- regulation of cyclin B-dependent kinase by tyrosine phosphorylation " +
+    "and dephosphorylation (by Wee1 kinase and Cdc25 phosphatase, respectively)." do
+    # The tyrosine-phosphorylated form is less active than the unphosphorylated form.
+    # Cyclin B-dependent kinase phosphorylates both Wee1 (inactivating it) and Cdc25
+    # (activating it), and these phosphorylations are reversed by Cdc14 phosphatase.
+  end
+
+  # The model is replete with positive feedback loops (CycB activates TFB, which drives synthesis
+  # of CycB; CKI inhibits CycB, which inhibits Cdh1), and negative feedback loops (CycB activates
+  # APC, which activates Cdc20, which degrades CycB; CycB activates Cdc20, which activates Cdc14,
+  # which opposes CycB; TFE drives synthesis of CycA, which inhibits TFE). These complex, inter-
+  # woven feedback loops create the interesting dynamical properties of the control system, which
+  # account for the characteristic features of cell cycle regulation, as we intend to show.
+end

metadata

@@ -0,0 +1,92 @@
+--- !ruby/object:Gem::Specification
+name: cell_cycle
+version: !ruby/object:Gem::Version
+  version: 0.0.2
+platform: ruby
+authors:
+- boris
+autorequire: 
+bindir: bin
+cert_chain: []
+date: 2014-10-14 00:00:00.000000000 Z
+dependencies:
+- !ruby/object:Gem::Dependency
+  name: bundler
+  requirement: !ruby/object:Gem::Requirement
+    requirements:
+    - - "~>"
+      - !ruby/object:Gem::Version
+        version: '1.6'
+  type: :development
+  prerelease: false
+  version_requirements: !ruby/object:Gem::Requirement
+    requirements:
+    - - "~>"
+      - !ruby/object:Gem::Version
+        version: '1.6'
+- !ruby/object:Gem::Dependency
+  name: rake
+  requirement: !ruby/object:Gem::Requirement
+    requirements:
+    - - ">="
+      - !ruby/object:Gem::Version
+        version: '0'
+  type: :development
+  prerelease: false
+  version_requirements: !ruby/object:Gem::Requirement
+    requirements:
+    - - ">="
+      - !ruby/object:Gem::Version
+        version: '0'
+description: 'Eukaryotic cell cycle modelled at different levels of precision. Has
+  two levels at the moment: Simple and Virginia Tech.'
+email:
+- '"boris@iis.sinica.edu.tw"'
+executables:
+- run_virginia
+extensions: []
+extra_rdoc_files: []
+files:
+- ".gitignore"
+- ACKNOWLEDGMENT.txt
+- Gemfile
+- LICENSE.txt
+- README.md
+- Rakefile
+- bin/run_virginia
+- cell_cycle.gemspec
+- lib/cell_cycle.rb
+- lib/cell_cycle/alternative_syntax_for_transitions.rb
+- lib/cell_cycle/simple.rb
+- lib/cell_cycle/version.rb
+- lib/cell_cycle/virginia_tech.rb
+- lib/cell_cycle/virginia_tech/mammalian_constants.rb
+- test/simple_test.rb
+- test/virginia_test.rb
+homepage: ''
+licenses:
+- MIT
+metadata: {}
+post_install_message: 
+rdoc_options: []
+require_paths:
+- lib
+required_ruby_version: !ruby/object:Gem::Requirement
+  requirements:
+  - - ">="
+    - !ruby/object:Gem::Version
+      version: '0'
+required_rubygems_version: !ruby/object:Gem::Requirement
+  requirements:
+  - - ">="
+    - !ruby/object:Gem::Version
+      version: '0'
+requirements: []
+rubyforge_project: 
+rubygems_version: 2.2.2
+signing_key: 
+specification_version: 4
+summary: A model of eukaryotic cell cycle.
+test_files:
+- test/simple_test.rb
+- test/virginia_test.rb