initial commit

3 files changed, 270 insertions, 0 deletions

diff --git a/application.rb b/application.rb
new file mode 100644
index 0000000..09f3188
--- /dev/null
+++ b/application.rb
@@ -0,0 +1,21 @@
+require 'sinatra'
+require "sinatra/reloader" 
+require "haml"
+require 'yaml'
+require "./pubchem.rb"
+also_reload './pubchem.rb'
+
+get '/?' do
+=begin
+  @compound = PubChem::Compound.new
+  smiles = "OC(=O)C1=C(C=CC=C1)OC(=O)C"
+  #smiles = "c1cc(CC)ccc1"
+  #smiles = "CC(=O)Nc1ccc(O)cc1"
+  smiles = "C1=CC(=C(C=C1Cl)Cl)OCC(=O)O"
+  #@compound.from_smiles smiles
+  @compound.get_neighbors smiles
+  File.open("compound.yaml","w+"){|f| f.puts @compound.to_yaml}
+=end
+  @compound = YAML.load_file "compound.yaml"
+  haml :index
+end
diff --git a/pubchem.rb b/pubchem.rb
new file mode 100644
index 0000000..e2574d1
--- /dev/null
+++ b/pubchem.rb
@@ -0,0 +1,202 @@
+require '../opentox-client/lib/opentox-client.rb'
+require 'json'
+
+# get assay from endpoint
+# search in endpoint ontology
+#
+# get measurements
+# search for compound and assay 
+#
+# get affected pathways
+# search for compound and genes
+# identify affected pathways
+# identify relations between affected genes/pathways and endpoint
+#
+# get related assays
+# search for assays in ontology tree
+# search for compound and related assays
+#
+# get similar compounds
+# search for similar compounds
+
+module PubChem
+
+  def pubchem_search url
+    puts url
+    #json =  RestClient.get url, :accept => "application/json", :timeout => 90000000
+    json =  `curl "#{url}"`#, :accept => "application/json", :timeout => 90000000
+    @result = JSON.parse json
+  end
+
+  class Assay
+    attr_accessor :aid
+  end
+
+  class Result
+    attr_accessor :aid, :cid, :sid
+  end
+
+  class Substance
+  end
+
+  class Compound
+    # doc @ http://pubchem.ncbi.nlm.nih.gov/pug_rest/
+    include OpenTox
+    include PubChem
+    attr_accessor :result, :cid, :neighbors, :tanimoto
+    
+    def initialize 
+      @uri = "http://pubchem.ncbi.nlm.nih.gov/rest/pug/"
+      @similarity_threshold = 95
+      @summary = []
+      @neighbors = []
+    end
+
+    def to_smiles
+      RestClient.get(File.join(@uri, "compound", "cid", @cid, "property", "CanonicalSMILES", "TXT")).strip
+    end
+
+    def name
+      RestClient.get(File.join(@uri, "compound", "cid", @cid, "property", "IUPACName", "TXT")).strip
+    end
+
+    def image
+      File.join @uri, "compound", "cid", @cid, "PNG?record_type=3d&image_size=small"
+    end
+
+    def properties
+      properties = [
+        "XLogP",
+        "ExactMass",
+        "MonoisotopicMass",
+        "TPSA",
+        "Complexity",
+        "Charge",
+        "HBondDonorCount",
+        "HBondAcceptorCount",
+        "RotatableBondCount",
+        "HeavyAtomCount",
+        "IsotopeAtomCount",
+        "AtomStereoCount",
+        "DefinedAtomStereoCount",
+        "UndefinedAtomStereoCount",
+        "BondStereoCount",
+        "DefinedBondStereoCount",
+        "UndefinedBondStereoCount",
+        "CovalentUnitCount",
+        "Volume3D",
+        "XStericQuadrupole3D",
+        "YStericQuadrupole3D",
+        "ZStericQuadrupole3D",
+        "FeatureCount3D",
+        "FeatureAcceptorCount3D",
+        "FeatureDonorCount3D",
+        "FeatureAnionCount3D",
+        "FeatureCationCount3D",
+        "FeatureRingCount3D",
+        "FeatureHydrophobeCount3D",
+        "ConformerModelRMSD3D",
+        "EffectiveRotorCount3D",
+        "ConformerCount3D",
+      ]
+      pubchem_search File.join(@uri, "compound", "cid", @cid, "property", properties.join(","), "JSON")
+      @result["PropertyTable"]["Properties"].first
+    end
+
+    def from_smiles smiles
+      pubchem_search File.join(@uri, "compound", "smiles", smiles, "assaysummary", "JSON")
+      from_summary @result["Table"]["Columns"]["Column"], @result["Table"]["Row"].collect{|cell| cell.values.flatten}
+    end
+
+    def from_summary columns, table
+      table.each do |row|
+        @summary << {}
+        row.each_with_index do |cell,i|
+          if columns[i] == "CID" 
+            @cid = cell if @cid.nil?
+          else
+            cell.blank? ?  @summary.last[columns[i]] = nil : @summary.last[columns[i]] = cell
+          end
+        end
+      end
+    end
+
+    def active_assays
+      @summary.collect{|a| a if a["Activity Outcome"] == "active"}.compact
+    end
+
+    def inactive_assays
+      @summary.collect{|a| a if a["Activity Outcome"] == "inactive"}.compact
+    end
+
+    def targets
+      active_assays.collect{|a| a["Target Name"]}.compact
+    end
+
+    def non_targets
+      inactive_assays.collect{|a| a["Target Name"]}.compact
+    end
+
+    def assay_similarity compound
+      a1 = active_assays.collect{|a| a["Assay Name"]}
+      a2 = compound.active_assays.collect{|a| a["Assay Name"]}
+      i1 = inactive_assays.collect{|a| a["Assay Name"]}
+      i2 = compound.inactive_assays.collect{|a| a["Assay Name"]}
+      self_assays = a1 + i1
+      compound_assays = a2 + i2
+      common_assays = self_assays & compound_assays
+      same_outcome = (a1 & a2) + (i1 & i2)
+      same_outcome.size.to_f/common_assays.size
+    end
+
+    def target_similarity compound
+      self_assays = targets + non_targets
+      compound_assays = compound.targets + compound.non_targets
+      common_assays = self_assays & compound_assays
+      same_outcome = (targets & compound.targets) + (non_targets & compound.non_targets)
+      same_outcome.size.to_f/common_assays.size
+    end
+
+    def assay_genes
+      active = []
+      @aids[:active].each do |aid|
+        begin
+        pubchem_search File.join(@uri, "assay", "aid", aid.to_s, "genes", "JSON")
+        active << @result["InformationList"]["Information"].collect{|i| i["GeneID"]}.flatten
+        rescue; end
+      end
+      @aids[:inactive].each do |aid|
+        begin
+        pubchem_search File.join(@uri, "assay", "aid", aid.to_s, "genes", "JSON")
+        inactive << @result["InformationList"]["Information"].collect{|i| i["GeneID"]}.flatten
+        rescue; end
+      end
+      {:active => active, :inactive => inactive } 
+    end
+
+    def get_neighbors smiles
+      pubchem_search File.join(@uri, "compound", "similarity", "smiles", smiles, "JSON")+"?Threshold=#{@similarity_threshold}&MaxRecords=250"
+      listkey = @result["Waiting"]["ListKey"]
+      while @result["Waiting"] do
+        sleep 1
+        pubchem_search File.join(@uri, "compound", "listkey", listkey, "assaysummary", "JSON")
+      end
+      File.open("search.yaml","w+"){|s| s.puts @result.to_yaml}
+      columns = @result["Table"]["Columns"]["Column"]
+      table = @result["Table"]["Row"].collect{|cell| cell.values.flatten}
+      cid_idx = columns.index("CID")
+      cids = table.collect{|r| r[cid_idx]}.uniq
+      cids.each do |cid|
+        tab = table.collect{|r| r if r[cid_idx] == cid}.compact
+        c = PubChem::Compound.new
+        c.from_summary columns, tab
+        @neighbors << c unless (c.targets + c.active_assays).flatten.compact.empty?
+      end
+      File.open("smiles.smi","w+"){|f| f.puts @neighbors.collect{|n| n.to_smiles}.join("\n")}
+      `babel smiles.smi -ofpt 2>/dev/null| grep Tanimoto|cut -d "=" -f2`.split("\n").each_with_index do |t,i|
+        @neighbors[i].tanimoto = t.strip.to_f
+      end
+    end
+  end
+end
+
diff --git a/views/index.haml b/views/index.haml
new file mode 100644
index 0000000..c8481c3
--- /dev/null
+++ b/views/index.haml
@@ -0,0 +1,47 @@
+!!! 5
+= @compound.neighbors.size
+%table
+  %tr
+    %th Structure
+    %th Properties
+    %th Targets
+    %th Assays
+  - @compound.neighbors.each do |neighbor|
+    %tr
+      %td
+        = neighbor.name
+        %img{:src => neighbor.image}
+        %dl
+          %dt Similarity
+          %dd
+            = neighbor.tanimoto
+      %td
+        %dl
+          - neighbor.properties.each do |p,v|
+            %dt 
+              = p
+            %dd
+              = v
+      %td
+        %dl
+          %dt Similarity
+          %dd
+            = neighbor.target_similarity @compound.neighbors.first
+          %dt Targets
+          %dd
+            = neighbor.targets.uniq
+          %dt Total
+          %dd
+            = neighbor.targets.size + neighbor.non_targets.size
+      %td
+        %dl
+          %dt Similarity
+          %dd
+            = neighbor.assay_similarity @compound.neighbors.first
+          %dt Active
+          %dd
+            = neighbor.active_assays.collect{|a| a["Assay Name"]}
+          %dt Total
+          %dd
+            = neighbor.active_assays.size + neighbor.inactive_assays.size
+            =# neighbor.inactive_assays.collect{|a| a["Assay Name"]}