From c38f9f2e4c2dec4ef163c6c76d64f5dbf4974a5a Mon Sep 17 00:00:00 2001
From: Christoph Helma <helma@in-silico.ch>
Date: Wed, 21 Nov 2012 10:09:48 +0100
Subject: Initial GUI

---
 Gemfile                      |   6 +
 VERSION                      |   1 +
 aop.gemspec                  |  27 ++++
 application.rb               | 197 ++++++++++++++++++++++++++---
 config.ru                    |   6 +
 false_positives.rb           |  39 ++++++
 pubchem-test.rb              |   8 +-
 pubchem.rb                   | 295 +++++++++++++++++++++++++++++--------------
 stat.rb                      |  30 +++++
 unicorn.rb                   |   1 +
 validation.rb                |  35 +++++
 views/assays.haml            |   6 +
 views/compound.haml          |  46 +++++++
 views/fp.haml                |  41 ++++++
 views/index.haml             |  27 ----
 views/layout.haml            |  26 ++++
 views/neighbors.haml         |  43 +++++++
 views/predicted_assays.haml  |   6 +
 views/predicted_targets.haml |   6 +
 views/select.haml            |   8 ++
 views/targets.haml           |   6 +
 21 files changed, 718 insertions(+), 142 deletions(-)
 create mode 100644 Gemfile
 create mode 100644 VERSION
 create mode 100644 aop.gemspec
 create mode 100644 config.ru
 create mode 100644 false_positives.rb
 create mode 100755 stat.rb
 create mode 100644 unicorn.rb
 create mode 100644 validation.rb
 create mode 100644 views/assays.haml
 create mode 100644 views/compound.haml
 create mode 100644 views/fp.haml
 create mode 100644 views/layout.haml
 create mode 100644 views/neighbors.haml
 create mode 100644 views/predicted_assays.haml
 create mode 100644 views/predicted_targets.haml
 create mode 100644 views/select.haml
 create mode 100644 views/targets.haml

diff --git a/Gemfile b/Gemfile
new file mode 100644
index 0000000..48f78eb
--- /dev/null
+++ b/Gemfile
@@ -0,0 +1,6 @@
+source :gemcutter
+gemspec
+gem "haml"
+gem "dalli"
+gem "opentox-server", :path => "../opentox-server"
+gem "opentox-client", :path => "../opentox-client"
diff --git a/VERSION b/VERSION
new file mode 100644
index 0000000..3be2757
--- /dev/null
+++ b/VERSION
@@ -0,0 +1 @@
+0.0.1pre1
diff --git a/aop.gemspec b/aop.gemspec
new file mode 100644
index 0000000..fe90a75
--- /dev/null
+++ b/aop.gemspec
@@ -0,0 +1,27 @@
+# -*- encoding: utf-8 -*-
+$:.push File.expand_path("../lib", __FILE__)
+
+Gem::Specification.new do |s|
+  s.name        = "aop"
+  s.version     = File.read("./VERSION")
+  s.authors     = ["Christoph Helma","Denis Gebele","Micha Rautenberg"]
+  s.email       = ["helma@in-silico.ch","gebele@in-silico.ch","rautenenberg@in-silico.ch"]
+  s.homepage    = "http://github.com/OpenTox/task"
+  s.summary     = %q{AOP GUI}
+  s.description = %q{AOP GUI}
+  s.license     = 'GPL-3'
+  #s.platform    = Gem::Platform::CURRENT
+
+  s.rubyforge_project = "aop"
+
+  s.files         = `git ls-files`.split("\n")
+  #s.test_files    = `git ls-files -- {test,spec,features}/*`.split("\n")
+  #s.executables   = `git ls-files -- bin/*`.split("\n").map{ |f| File.basename(f) }
+  #s.require_paths = ["lib"]
+  s.required_ruby_version = '>= 1.9.2'
+
+  # specify any dependencies here; for example:
+  s.add_runtime_dependency "opentox-server"
+  s.post_install_message = "Please configure your service in ~/.opentox/config/aop.rb"
+end
+
diff --git a/application.rb b/application.rb
index 2a77013..a3d46c3 100644
--- a/application.rb
+++ b/application.rb
@@ -1,22 +1,183 @@
-require 'sinatra'
-require "sinatra/reloader" 
-require "haml"
-require 'yaml'
 require "./pubchem.rb"
-also_reload './pubchem.rb'
-
-get '/?' do
-  #@neighbors = OpenTox::PubChemNeighbors.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
-  #@neighbors.from_smiles smiles
+require 'rack/session/dalli'
+module OpenTox
+  class Application < Service
+    set :static, true
+    set :root, File.dirname(__FILE__)
+    also_reload './pubchem.rb'
+    #enable :sessions
+    use Rack::Session::Dalli, :cache => Dalli::Client.new
+
+    @@pug_uri = "http://pubchem.ncbi.nlm.nih.gov/rest/pug/"
+
+    helpers do
+
 =begin
-  File.open("compound.yaml","w+"){|f| f.puts @compound.to_yaml}
-  @compound = YAML.load_file "compound.yaml"
+      def pubchem_search url
+        attempts = 0
+        result = nil
+        begin
+          attempts += 1
+          json = RestClient.get url, :timeout => 90000000
+          result = JSON.parse json
+          while result["Waiting"] do
+            sleep 2
+            listkey = result["Waiting"]["ListKey"]
+            result = pubchem_search File.join(@pug_uri, "compound", "listkey", listkey, "cids", "JSON")
+          end
+        rescue
+          if $!.message =~ /Timeout/i and attempts < 4
+            sleep 2
+            retry
+          elsif $!.message =~ /Timeout/i and attempts >= 4
+            File.open("timeouts","a+"){|f| f.puts url}
+            puts url
+            puts $!.message
+          elsif $!.message.match /404/
+            #not_found_error #TODO
+          else
+            puts url
+            puts $!.message
+          end
+        end
+      end
 =end
-  @neighbors = YAML.load_file "search.yaml"
-  haml :index
+
+      def image_uri cid
+        File.join @@pug_uri, "compound", "cid", cid, "PNG"#?record_type=3d&image_size=small"
+      end
+
+    end
+
+    before '/cid/:cid/*' do
+      session[:compound] = PubChemCompound.new params[:cid] unless session[:compound] and session[:compound].cid == params[:cid]
+    end
+
+    get '/?' do
+      haml :index
+    end
+
+    get '/cid/:cid/?' do
+      session[:compound] = PubChemCompound.new params[:cid]
+      haml :compound
+    end
+
+    get '/search/?' do
+      #begin
+        cids = RestClientWrapper.get(File.join(@@pug_uri,"compound","name",URI.escape(params[:name]),"cids","TXT")).split("\n")
+        if cids.size == 1
+          session[:compound] = PubChemCompound.new cids.first
+          haml :compound
+        elsif cids.size > 1
+          @compounds = cids.collect{|cid| PubChemCompound.new cid }
+          haml :select
+        end
+      #rescue
+        #haml :not_found
+      #end
+    end
+
+    get '/cid/:cid/targets/?' do
+      if params[:cid] == session[:compound].cid
+        @assays = session[:compound].targets
+      else
+        @assays = PubChemCompound.new(params[:cid]).targets
+      end
+      haml :targets, :layout => false
+    end
+
+    get '/cid/:cid/nontargets/?' do
+      if params[:cid] == session[:compound].cid
+        @assays = session[:compound].non_targets
+      else
+        @assays = PubChemCompound.new(params[:cid]).non_targets
+      end
+      haml :targets, :layout => false
+    end
+
+    get '/cid/:cid/other_active_assays/?' do
+      if params[:cid] == session[:compound].cid
+        @assays = session[:compound].active_assays - session[:compound].targets
+      else
+        compound = PubChemCompound.new(params[:cid])
+        @assays = compound.active_assays - compound.targets
+      end
+      haml :assays, :layout => false
+    end
+
+    get '/cid/:cid/other_inactive_assays/?' do
+      if params[:cid] == session[:compound].cid
+        @assays = session[:compound].inactive_assays - session[:compound].non_targets
+      else
+        compound = PubChemCompound.new(params[:cid])
+        @assays = compound.inactive_assays - compound.non_targets
+      end
+      haml :assays, :layout => false
+    end
+
+    get '/cid/:cid/predicted_targets/?' do
+      if params[:cid] == session[:compound].cid
+        @assays = session[:compound].predicted_targets
+      else
+        @assays = PubChemCompound.new(params[:cid]).predicted_targets
+      end
+      haml :predicted_targets, :layout => false
+    end
+
+    get '/cid/:cid/predicted_nontargets/?' do
+      if params[:cid] == session[:compound].cid
+        @assays = session[:compound].predicted_non_targets
+      else
+        @assays = PubChemCompound.new(params[:cid]).predicted_non_targets
+      end
+      haml :predicted_targets, :layout => false
+    end
+
+    get '/cid/:cid/other_predicted_active_assays/?' do
+      if params[:cid] == session[:compound].cid
+        @assays = session[:compound].predicted_active_assays - session[:compound].predicted_targets
+      else
+        compound = PubChemCompound.new(params[:cid])
+        @assays = compound.predicted_active_assays - compound.predicted_targets
+      end
+      haml :predicted_assays, :layout => false
+    end
+
+    get '/cid/:cid/other_predicted_inactive_assays/?' do
+      if params[:cid] == session[:compound].cid
+        @assays = session[:compound].predicted_inactive_assays - session[:compound].predicted_non_targets
+      else
+        compound = PubChemCompound.new(params[:cid])
+        @assays = compound.predicted_inactive_assays - compound.predicted_non_targets
+      end
+      haml :assays, :layout => false
+    end
+
+    get '/cid/:cid/neighbors/?' do
+      haml :neighbors, :layout => false
+    end
+
+
+    get '/cid/:cid/cosine/:cid2/?' do
+      session[:compound].cosine(PubChemCompound.new(params[:cid2])).to_s
+    end
+
+    get '/fp/?' do
+      @fp = []
+      YAML.load_file("false_positives.yaml").each do |pred|
+        pred[:fp_targets].each do |gi,t|
+          @fp << {
+            "CID" => pred[:cid],
+            "Target GI" => gi,
+            "p_active" => t[:p][:active].first, 
+            "p_inactive" => t[:p][:inactive].first, 
+            :assays => t[:measured],
+            :neighbors => t[:neighbors]
+          }
+        end
+      end
+      @fp.sort!{|a,b| b["p_active"] <=> a["p_active"]}
+      haml :fp
+    end
+  end
 end
diff --git a/config.ru b/config.ru
new file mode 100644
index 0000000..4050809
--- /dev/null
+++ b/config.ru
@@ -0,0 +1,6 @@
+SERVICE = "aop"
+require 'bundler'
+Bundler.require
+timeout = 600
+require './application.rb'
+run OpenTox::Application
diff --git a/false_positives.rb b/false_positives.rb
new file mode 100644
index 0000000..9453679
--- /dev/null
+++ b/false_positives.rb
@@ -0,0 +1,39 @@
+#!/usr/bin/env ruby
+require "./pubchem.rb"
+
+false_positives = YAML.load_file("false_positives.yaml")
+#false_positives = []
+until false_positives.size > 100 do
+  result = {}
+  @compound = OpenTox::PubChemCompound.new
+  # http://www.ncbi.nlm.nih.gov/sites/entrez?term=all%5Bfilt%5D&cmd=search&db=pccompound
+  @compound.cid = Random.new.rand(1..35611104)
+  puts @compound.cid
+  if @compound.targets and @compound.non_targets and !(@compound.targets + @compound.non_targets).empty?
+    puts "predicting ..."
+    result[:cid] = @compound.cid
+    measured_non_targets = @compound.non_targets.collect{|t| t["Target GI"]}.compact.uniq
+    predicted_targets = @compound.predicted_targets.collect{|t| t[:target_gi] if t[:prediction] == "active"}.compact.uniq
+
+    result[:fp_targets] = {}
+    (predicted_targets & measured_non_targets).each do |gi|
+      result[:fp_targets][gi] = {:p => {:active => nil, :inactive => nil}, :measured => [], :neighbors => []}
+      result[:fp_targets][gi][:measured] = @compound.inactive_assays.select{|a| a["Target GI"] == gi}
+      result[:fp_targets][gi][:p][:active] = @compound.predicted_targets.collect{|t| t[:p_active] if t[:target_gi] == gi}.compact.uniq
+      result[:fp_targets][gi][:p][:inactive] = @compound.predicted_targets.collect{|t| t[:p_inactive] if t[:target_gi] == gi}.compact.uniq 
+
+      @compound.neighbors.select{|n| n.assays.collect{|a| a["Target GI"]}.include? gi }.each do |neighbor|
+        result[:fp_targets][gi][:neighbors] << {
+          :cid => neighbor.cid,
+          :similarity => neighbor.similarity,
+          :assays => neighbor.assays.select{|a| a["Target GI"] == gi }
+        }
+      end
+    end
+    unless result[:fp_targets].empty?
+      false_positives << result
+      File.open("false_positives.yaml","w+") {|f| f.puts false_positives.to_yaml}
+    end
+  end
+end
+
diff --git a/pubchem-test.rb b/pubchem-test.rb
index 273698e..a3e7799 100644
--- a/pubchem-test.rb
+++ b/pubchem-test.rb
@@ -7,7 +7,7 @@ class AOPTest < Test::Unit::TestCase
 
   def setup
     @pug_uri = "http://pubchem.ncbi.nlm.nih.gov/rest/pug/"
-    @compound = OpenTox::PubChemCompound.new
+    @compound = OpenTox::PubChemCompound.new #3036
     @compound.cid = 1983
     #@compound.from_name "2,4-D"
   end
@@ -18,8 +18,9 @@ class AOPTest < Test::Unit::TestCase
     puts @compound.to_smiles
     puts "measured targets"
     puts @compound.targets.collect{|t| t["Target Name"]}.to_yaml
+=begin
     puts "predicted targets"
-    puts @compound.predicted_targets.select{|t| t[:prediction] == "active"}.to_yaml
+    puts @compound.predicted_targets.select{|t| t[:prediction] == "active"}.size
 
     puts "predicted non_targets"
     puts @compound.predicted_targets.select{|t| t[:prediction] == "inactive"}.size
@@ -38,8 +39,11 @@ class AOPTest < Test::Unit::TestCase
     puts (predicted_nontarget_gis - measured_nontarget_gis).size
     print "incorrect predicted targets: "
     puts (measured_nontarget_gis & predicted_target_gis).size
+    puts (measured_nontarget_gis & predicted_target_gis).sort.to_yaml
+    puts @compound.predicted_targets.select{|t| t[:prediction] == "active"}.to_yaml
     print "incorrect predicted non-targets: "
     puts (measured_target_gis & predicted_nontarget_gis).size
+=end
 =begin
     @compound.neighbors.each do |n|
       #print n.cid
diff --git a/pubchem.rb b/pubchem.rb
index 891110c..a6893fb 100644
--- a/pubchem.rb
+++ b/pubchem.rb
@@ -1,154 +1,221 @@
 require '../opentox-client/lib/opentox-client.rb'
 require 'json'
+require 'base64'
 
 def Math.gauss(x, sigma = 0.3) 
   d = 1.0 - x.to_f
   Math.exp(-(d*d)/(2*sigma*sigma))
 end
 
-module PubChem
-
-  attr_accessor :result
-
-  def initialize
-    @pug_uri = "http://pubchem.ncbi.nlm.nih.gov/rest/pug/"
-  end
-
-  def pubchem_search url
-    json =  RestClient.get url#, :accept => "application/json", :timeout => 90000000
-    @result = JSON.parse json
-  rescue
-    puts url
-    puts $!.message
-    @result = nil
-  end
-
-end
-
 module OpenTox
 
+  # doc @ http://pubchem.ncbi.nlm.nih.gov/pug_rest/
   class PubChemCompound < Compound
-    include PubChem
-    # doc @ http://pubchem.ncbi.nlm.nih.gov/pug_rest/
     attr_writer :cid
     attr_accessor :similarity, :p, :assays
     
-    def initialize 
-      super
-      @summary = []
-      @similarity_threshold = 75
-      @neighbors = []
-      @predicted_targets = []
+    def initialize cid=nil
+      @pug_uri = "http://pubchem.ncbi.nlm.nih.gov/rest/pug/"
+      @cid = cid
+      @assays = nil
+      @similarity_threshold = 85
+      @neighbors = nil
+      @predicted_assays = nil
+      #@predicted_targets = nil
+      #@priors = {}
+      #@priors = JSON.parse(File.read("priors.json"))
     end
 
-    def from_name name
-      @inchi = RestClientWrapper.get File.join(CACTUS_URI,URI.escape(name),"stdinchi")
+    def fingerprint
+      unless @fingerprint
+        begin
+          # ftp://ftp.ncbi.nlm.nih.gov/pubchem/specifications/pubchem_fingerprints.txt
+          base64key = `curl http://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/#{cid}/SDF|grep -A1 PUBCHEM_CACTVS_SUBSKEYS|sed '1d'`.chomp
+          @fingerprint = Base64.decode64(base64key)[4..-1].unpack("B*").first[0..-8].split(//).collect{|c| c == "1"}
+        rescue
+        end
+      end
+      @fingerprint
+    end
+
+    def self.from_name name
+      pug_uri = "http://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/name"
+      compounds = []
+      session[:name] = name
+      cid = RestClientWrapper.get(File.join(pug_uri,URI.escape(name),"cids","TXT"))
+      #puts response
+      #response.split("\n") do |cid|
+        puts cid
+        compound = OpenTox::PubChemCompound.new
+        compound.cid = cid.chomp
+        compounds << compound
+      #end
+      compounds
     end
 
     def neighbors
-      if @neighbors.empty?
-        pubchem_search File.join(@pug_uri, "compound", "similarity", "cid", cid.to_s, "JSON")+"?Threshold=#{@similarity_threshold}&MaxRecords=100"
-        listkey = @result["Waiting"]["ListKey"]
-        while @result["Waiting"] do
-          sleep 1
-          pubchem_search File.join(@pug_uri, "compound", "listkey", listkey, "assaysummary", "JSON")
+      unless @neighbors
+        @neighbors = []
+        result = pubchem_search File.join(@pug_uri, "compound", "similarity", "cid", cid.to_s, "JSON")+"?Threshold=#{@similarity_threshold}&MaxRecords=100"
+        while result["Waiting"] do
+          sleep 2
+          listkey = result["Waiting"]["ListKey"]
+          result = pubchem_search File.join(@pug_uri, "compound", "listkey", listkey, "cids", "JSON")
+          #result = pubchem_search File.join(@pug_uri, "compound", "listkey", listkey, "assaysummary", "JSON")
         end
-        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|
+        puts "Neighbor CIDs received"
+        result["IdentifierList"]["CID"].each do |cid|
           unless cid.to_s == @cid.to_s
-            tab = table.collect{|r| r if r[cid_idx] == cid}.compact
-            c = PubChemCompound.new
-            c.extract_result columns, tab
-            c.similarity = tanimoto c
-            @neighbors << c unless (c.targets + c.non_targets).empty?
+            c = PubChemCompound.new cid.to_s
+            @neighbors << c if c.assays #and !(c.targets + c.non_targets).empty?
+          end
+        end if result and result["IdentifierList"]
+=begin
+        if result and result["Table"]
+          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|
+            unless cid.to_s == @cid.to_s
+              tab = table.collect{|r| r if r[cid_idx] == cid}.compact
+              c = PubChemCompound.new
+              c.extract_result columns, tab
+              c.similarity = tanimoto c
+              @neighbors << c unless (c.targets + c.non_targets).empty?
+            end
           end
         end
-        @neighbors.sort!{|a,b| b.similarity <=> a.similarity}
+=end
+        #@neighbors.sort!{|a,b| b.similarity <=> a.similarity}
       end
       @neighbors
     end
 
-    def summary
-      if @summary.empty?
-        pubchem_search File.join(@pug_uri, "compound", "cid", cid.to_s, "assaysummary", "JSON")
-        extract_result @result["Table"]["Columns"]["Column"], @result["Table"]["Row"].collect{|cell| cell.values.flatten}
+    def assays
+      unless @assays
+        result = pubchem_search File.join(@pug_uri, "compound", "cid", cid.to_s, "assaysummary", "JSON")
+        extract_result result["Table"]["Columns"]["Column"], result["Table"]["Row"].collect{|cell| cell.values.flatten} if result and result["Table"]
       end
-      @summary
+      @assays
     end
 
     def active_assays
-      summary.select{|a| a["Activity Outcome"] == "active"}
+      assays.select{|a| a["Activity Outcome"] == "active"} if assays
     end
 
     def inactive_assays
-      summary.select{|a| a["Activity Outcome"] == "inactive"}
+      assays.select{|a| a["Activity Outcome"] == "inactive"} if assays
     end
 
     def targets
-      active_assays.select{|a| a["Target GI"]}
+      active_assays.select{|a| a["Target GI"]} if assays
     end
 
     def non_targets
-      inactive_assays.select{|a| a["Target GI"]}
+      inactive_assays.select{|a| a["Target GI"]} if assays
     end
 
-    def predicted_targets
-      if @predicted_targets.empty?
-        target_gis = neighbors.collect{|n| n.summary.collect{|a| a["Target GI"]}}.flatten.compact.uniq
-        target_gis.each do |gid|
-          target = {:target_gi => gid}
+    def predicted_assays
+      unless @predicted_assays
+        @predicted_assays = []
+        neighbors.collect{|n| n.assays.collect{|a| a["AID"]}}.flatten.compact.uniq.each do |aid|
+          predicted_assay = {"AID" => aid}
           neighbors.each do |neighbor|
-            if neighbor.similarity > 0.5 # avoid downweighting
-              search = neighbor.summary.select{|a| a["Target GI"] == gid}
-              unless search.empty? or search.size == 1
-                print "+++ ("
-                print search.size
-                puts ")"
-                puts search.inspect
-              end
+            if similarity(neighbor) > 0.5 # avoid downweighting
+              search = neighbor.assays.select{|a| a["AID"] == aid}
               search.each do |assay|
-                target[:aid] ||= assay["AID"]
-                target[:name] ||= assay["Target Name"]
-                target[:assay_name] ||= assay["Assay Name"]
-                target[:active_similarities] ||= []
-                target[:inactive_similarities] ||= []
+                predicted_assay["Target GI"] ||= assay["Target GI"]
+                predicted_assay["Target Name"] ||= assay["Target Name"]
+                predicted_assay["Assay Name"] ||= assay["Assay Name"]
+                predicted_assay[:active_similarities] ||= []
+                predicted_assay[:inactive_similarities] ||= []
 
                 if assay["Activity Outcome"] == "active"
-                  target[:p_active] ? target[:p_active] = target[:p_active]*neighbor.similarity : target[:p_active] = neighbor.similarity
-                  target[:p_inactive] ? target[:p_inactive] = target[:p_inactive]*(1-neighbor.similarity) : target[:p_inactive] = 1-neighbor.similarity
-                  target[:active_similarities] << neighbor.similarity
+                  predicted_assay[:p_active] ? predicted_assay[:p_active] = predicted_assay[:p_active]*similarity(neighbor) : predicted_assay[:p_active] = similarity(neighbor)
+                  predicted_assay[:p_inactive] ? predicted_assay[:p_inactive] = predicted_assay[:p_inactive]*(1-similarity(neighbor)) : predicted_assay[:p_inactive] = 1-similarity(neighbor)
+                  predicted_assay[:active_similarities] << similarity(neighbor)
                 elsif assay["Activity Outcome"] == "inactive"
-                  target[:p_active] ? target[:p_active] = target[:p_active]*(1-neighbor.similarity) : target[:p_active] = 1-neighbor.similarity
-                  target[:p_inactive] ? target[:p_inactive] = target[:p_inactive]*neighbor.similarity : target[:p_inactive] = neighbor.similarity
-                  target[:inactive_similarities] << neighbor.similarity
+                  predicted_assay[:p_active] ? predicted_assay[:p_active] = predicted_assay[:p_active]*(1-similarity(neighbor)) : predicted_assay[:p_active] = 1-similarity(neighbor)
+                  predicted_assay[:p_inactive] ? predicted_assay[:p_inactive] = predicted_assay[:p_inactive]*similarity(neighbor) : predicted_assay[:p_inactive] = similarity(neighbor)
+                  predicted_assay[:inactive_similarities] << similarity(neighbor)
                 end
               end
             end
           end
-          if target[:p_active] and target[:p_inactive] and target[:p_active] + target[:p_inactive] != 0
-            target[:p_active] = target[:p_active]/(target[:p_active]+target[:p_inactive])
-            target[:p_inactive] = target[:p_inactive]/(target[:p_active]+target[:p_inactive])
-            if target[:p_active] > target[:p_inactive]
-              target[:prediction] = "active"
-            elsif target[:p_active] < target[:p_inactive]
-              target[:prediction] = "inactive"
+          if predicted_assay[:p_active] and predicted_assay[:p_inactive] and predicted_assay[:p_active] != 0 and predicted_assay[:p_inactive] != 0
+            predicted_assay[:p_active] = predicted_assay[:p_active]/(predicted_assay[:p_active]+predicted_assay[:p_inactive])
+            predicted_assay[:p_inactive] = predicted_assay[:p_inactive]/(predicted_assay[:p_active]+predicted_assay[:p_inactive])
+            if predicted_assay[:p_active] > predicted_assay[:p_inactive]
+              predicted_assay[:prediction] = "active"
+            elsif predicted_assay[:p_active] < predicted_assay[:p_inactive]
+              predicted_assay[:prediction] = "inactive"
             end
-            @predicted_targets << target
+            @predicted_assays << predicted_assay
           end
         end
-        @predicted_targets.sort{|a,b| b[:p_active] <=> a[:p_active]}
+        #@predicted_targets.sort{|a,b| b[:p_active] <=> a[:p_active]}
       end
-      @predicted_targets
+      @predicted_assays
+    end
+
+    def predicted_active_assays
+      predicted_assays.select{|a| a[:prediction] == "active"} if predicted_assays
+    end
+
+    def predicted_inactive_assays
+      predicted_assays.select{|a| a[:prediction] == "inactive"} if predicted_assays
+    end
+
+    def predicted_targets
+      predicted_active_assays.select{|a| a[:target_gi]} if predicted_assays
+    end
+
+    def predicted_non_targets
+      inactive_assays.select{|a| a[:target_gi]} if predicted_assays
     end
 
     def to_smiles
       RestClient.get(File.join(@pug_uri, "compound", "cid", cid.to_s, "property", "CanonicalSMILES", "TXT")).strip
     end
 
+    def image_uri
+      File.join @pug_uri, "compound", "cid", @cid, "PNG"#?record_type=3d&image_size=small"
+    end
+
+    def similarity compound
+      cosine compound
+    end
+
     def tanimoto compound
+      if fingerprint and compound.fingerprint
+        m11 = 0.0
+        m1 = 0.0
+        fingerprint.each_index do |i|
+          m11 += 1 if (@fingerprint[i] and compound.fingerprint[i])
+          m1 += 1 if (@fingerprint[i] or compound.fingerprint[i]) 
+        end
+        m11/m1
+      end
+    end
+
+    def cosine compound
+      if fingerprint and compound.fingerprint
+        m11 = 0.0
+        m01 = 0.0
+        m10 = 0.0
+        m00 = 0.0
+        fingerprint.each_index do |i|
+          m11 += 1 if (@fingerprint[i] and compound.fingerprint[i])
+          m01 += 1 if (!@fingerprint[i] and compound.fingerprint[i]) 
+          m10 += 1 if (@fingerprint[i] and !compound.fingerprint[i]) 
+          m00 += 1 if (!@fingerprint[i] and !compound.fingerprint[i]) 
+        end
+        m11/((m01+m11)*(m10+m11))**0.5
+      end
+    end
+
+=begin
       f1 = File.open(File.join(".","tmp",SecureRandom.uuid+".smi"),"w+")
       f1.puts to_smiles
       f1.close
@@ -160,20 +227,62 @@ module OpenTox
       File.delete(f2.path)
       sim
     end
+=end
+
+    def pubchem_search url
+      attempts = 0
+      begin
+        attempts += 1
+        json = RestClient.get url, :timeout => 90000000
+        puts url
+        JSON.parse json
+      rescue
+        if $!.message =~ /Timeout/i and attempts < 4
+          sleep 2
+          retry
+        elsif $!.message =~ /Timeout/i and attempts >= 4
+          File.open("timeouts","a+"){|f| f.puts url}
+          puts url
+          puts $!.message
+          nil
+        elsif $!.message.match /404/
+          nil
+        else
+          puts url
+          puts $!.message
+          nil
+        end
+      end
+    end
 
     def extract_result columns, table
+      @assays = []
       table.each do |row|
-        @summary << {}
+        @assays << {}
         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
+            cell.blank? ?  @assays.last[columns[i]] = nil : @assays.last[columns[i]] = cell
           end
         end
       end
     end
 
+    def priors aid
+      unless @priors[aid]
+        @priors[aid] = {"nr_active" => 0, "nr_inactive" => 0}
+        result = nil
+        result = pubchem_search File.join(@pug_uri, "assay", "aid", aid.to_s, "cids", "JSON?cids_type=active&list_return=listkey")
+        @priors[aid]["nr_active"] = result["IdentifierList"]["Size"].to_i if result
+        result = nil
+        result = pubchem_search File.join(@pug_uri, "assay", "aid", aid.to_s, "cids", "JSON?cids_type=inactive&list_return=listkey")
+        @priors[aid]["nr_inactive"] = result["IdentifierList"]["Size"].to_i if result
+        File.open("priors.json","w+"){|f| f.puts @priors.to_json}
+      end
+      @priors[aid]
+    end
+
 =begin
     def assay_summary assay
         if assay["Target GI"] and !@assays[assay["AID"]]
@@ -262,10 +371,6 @@ module OpenTox
     def to_name
       RestClient.get(File.join(@pug_uri, "compound", "cid", @cid, "property", "IUPACName", "TXT")).strip
     end
-
-    def to_image_uri
-      File.join @pug_uri, "compound", "cid", @cid, "PNG?record_type=3d&image_size=small"
-    end
 =end
 
   end
diff --git a/stat.rb b/stat.rb
new file mode 100755
index 0000000..9f590d8
--- /dev/null
+++ b/stat.rb
@@ -0,0 +1,30 @@
+#!/usr/bin/env ruby
+require 'yaml'
+
+stat = {:tp => 0, :tn => 0, :fp => 0, :fn => 0, :tp_p => [], :fp_p => []}
+thresh = 0.05
+Dir["./validation/*yaml"].each do |f|
+  data = YAML.load_file f
+  pa = data[:predicted][:active].select{|gi| data[:predicted][:p][gi][:p_active] > thresh }
+  pi = data[:predicted][:inactive].select{|gi| data[:predicted][:p][gi][:p_inactive] > thresh }
+  stat[:tp] += (pa & data[:measured][:active]).size
+  stat[:tn] += (pi & data[:measured][:inactive]).size
+  stat[:fp] += (pa & data[:measured][:inactive]).size
+  stat[:fn] += (pi & data[:measured][:active]).size
+  (pa & data[:measured][:active]).each{|gi| stat[:tp_p] << data[:predicted][:p][gi][:p_active] }
+  (pa & data[:measured][:inactive]).each{|gi| stat[:fp_p] << data[:predicted][:p][gi][:p_active] }
+end
+
+stat[:tp_p].sort!
+stat[:fp_p].sort!
+puts stat.to_yaml
+print "accuracy: "
+puts (stat[:tp]+stat[:tn])/(stat[:tp]+stat[:tn]+stat[:fp]+stat[:fn]).to_f
+print "sensitivity: "
+puts stat[:tp]/(stat[:tp]+stat[:fn]).to_f
+print "specificity: "
+puts stat[:tn]/(stat[:tn]+stat[:fp]).to_f
+print "positive predictive value: "
+puts stat[:tp]/(stat[:tp]+stat[:fp]).to_f
+print "negative predictive value: "
+puts stat[:tn]/(stat[:tn]+stat[:fn]).to_f
diff --git a/unicorn.rb b/unicorn.rb
new file mode 100644
index 0000000..59b9883
--- /dev/null
+++ b/unicorn.rb
@@ -0,0 +1 @@
+timeout 600
diff --git a/validation.rb b/validation.rb
new file mode 100644
index 0000000..0e95fc3
--- /dev/null
+++ b/validation.rb
@@ -0,0 +1,35 @@
+#!/usr/bin/env ruby
+require "./pubchem.rb"
+
+until Dir["./validation/*.yaml"].size > 1000 do
+#100.times do
+  result = {}
+  @compound = OpenTox::PubChemCompound.new
+  # http://www.ncbi.nlm.nih.gov/sites/entrez?term=all%5Bfilt%5D&cmd=search&db=pccompound
+  @compound.cid = Random.new.rand(1..35611104)
+  puts @compound.cid
+  unless File.exists?  "./validation/#{@compound.cid}.yaml"
+    if (@compound.targets + @compound.non_targets).size > 0
+    #if @compound.assays#.empty?
+      begin
+        puts "predicting ..."
+        result[:cid] = @compound.cid
+        result[:measured] = {}
+        result[:predicted] = {}
+        result[:measured][:active] = @compound.targets.collect{|t| t["Target GI"]}.compact.uniq
+        result[:measured][:inactive] = @compound.non_targets.collect{|t| t["Target GI"]}.compact.uniq
+        result[:predicted][:active] = @compound.predicted_targets.collect{|t| t[:target_gi] if t[:prediction] == "active"}.compact.uniq
+        result[:predicted][:inactive] = @compound.predicted_targets.collect{|t| t[:target_gi] if t[:prediction] == "inactive"}.compact.uniq
+        result[:predicted][:p] = {}
+        @compound.predicted_targets.each do |t|
+          result[:predicted][:p][t[:target_gi]] = {}
+          result[:predicted][:p][t[:target_gi]][:p_active] = t[:p_active]
+          result[:predicted][:p][t[:target_gi]][:p_inactive] = t[:p_inactive]
+        end
+        File.open("./validation/#{@compound.cid}.yaml","w+"){|f| f.puts result.to_yaml}
+        puts result.to_yaml
+      rescue
+      end
+    end
+  end
+end
diff --git a/views/assays.haml b/views/assays.haml
new file mode 100644
index 0000000..e995842
--- /dev/null
+++ b/views/assays.haml
@@ -0,0 +1,6 @@
+%ul
+  - @assays.each do |assay|
+    %li
+      %a{:href => "/aid/#{assay["AID"]}"} #{assay['Assay Name']}
+      AID:
+      = assay["AID"]
diff --git a/views/compound.haml b/views/compound.haml
new file mode 100644
index 0000000..7614142
--- /dev/null
+++ b/views/compound.haml
@@ -0,0 +1,46 @@
+:javascript
+  $(document).ready(function() {
+    display(".targets", "/cid/#{session[:compound].cid}/targets");
+    //display(".nontargets", "/cid/#{session[:compound].cid}/targets");
+    display(".active_assays", "/cid/#{session[:compound].cid}/other_active_assays");
+    //display(".inactive_assays", "/cid/#{session[:compound].cid}/other_active_assays");
+    display(".predicted_targets", "/cid/#{session[:compound].cid}/predicted_targets");
+    display(".predicted_active_assays", "/cid/#{session[:compound].cid}/other_predicted_active_assays");
+    display(".neighbors", "/cid/#{session[:compound].cid}/neighbors");
+  });
+
+%script{:type => "text/javascript", :src  => "sorttable.js"}
+%table{:class => "sortable"}
+  %tr
+    %th Structure
+    %th 
+    %th Targets (experimental data)
+    %th Other assays (experimental data)
+  %tr
+    %td{:valign => "top"}
+      %img{:src => session[:compound].image_uri}
+    %td
+    %td{:valign => "top"}
+      .targets
+      -# %h2 Non-Targets
+        .nontargets
+    %td{:valign => "top"}
+      .active_assays
+      -# %h2 Inactive assays
+        .inactive_assays
+  %tr
+    %th 
+    %th 
+    %th Targets (predicted)
+    %th Other assays (predicted)
+  %tr
+    %td
+    %td
+    %td{:valign => "top"}
+      .predicted_targets
+    %td{:valign => "top"}
+      .predicted_active_assays
+
+%h2 Neighbors
+.neighbors
+
diff --git a/views/fp.haml b/views/fp.haml
new file mode 100644
index 0000000..4bffba3
--- /dev/null
+++ b/views/fp.haml
@@ -0,0 +1,41 @@
+!!! 5
+%style{:type => "text/css" }
+  //dt { float: left; clear: left; width: 100px; text-align: right; font-weight: bold; color: green; }
+  //dt {  float: left; clear: left; text-align: left; font-weight: bold; color: green; }
+  table { border-top: 2px black }
+  dl {text-align:left;}
+  dt { display: inline; text-align: left; font-weight: bold; color: green; }
+  dt:after { content: ": "; }
+  dd {  display: inline; text-align: left; margin:0 }
+  dd:after { content: '\A'; white-space: pre; }
+- @fp.each do |p|
+  %table{:class => "sortable"}
+    %tr
+      %th
+        %img{:src => "http://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/#{p["CID"]}/PNG"}
+      %th
+        %dl
+          - [ "CID", "Target GI", "p_active", "p_inactive" ].each do |k|
+            %dt= k
+            %dd= p[k]
+      - p[:assays].each do |a|
+        %th
+          %dl
+            - a.each do |k,v|
+              %dt= k
+              %dd= v
+      - p[:neighbors].each do |n|
+        %tr
+          %td
+            %img{:src => "http://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/#{n[:cid]}/PNG"}
+          %td
+            %dl
+              - ["CID", "Similarity"].each do |k|
+                %dt= k
+                %dd= n[k.downcase.to_sym]
+          - n[:assays].each do |a|
+            %td
+              %dl
+                - a.each do |k,v|
+                  %dt= k
+                  %dd= v
diff --git a/views/index.haml b/views/index.haml
index b75a9ab..e69de29 100644
--- a/views/index.haml
+++ b/views/index.haml
@@ -1,27 +0,0 @@
-!!! 5
-%script{:type => "text/javascript", :src  => "sorttable.js"}
-%table{:class => "sortable"}
-  %tr
-    %th
-      = @neighbors.query.to_name
-      %br
-        %img{:src => @neighbors.query.to_image_uri}
-    %th Structure
-    %th Properties
-    %th Targets
-    %th Assays
-  - @neighbors.neighbors.each do |neighbor|
-    - sim = neighbor.structure_similarity @neighbors.query
-    %tr{:sorttable_customkey => sim}
-      %td
-        = neighbor.to_name
-        %br
-          %img{:src => neighbor.to_image_uri}
-      %td
-        = sim
-      %td
-        = neighbor.property_similarity @neighbors.query
-      %td
-        = neighbor.target_similarity @neighbors.query
-      %td
-        = neighbor.assay_similarity @neighbors.query
diff --git a/views/layout.haml b/views/layout.haml
new file mode 100644
index 0000000..8641692
--- /dev/null
+++ b/views/layout.haml
@@ -0,0 +1,26 @@
+!!! 5
+%html
+  %head
+    %script{:type => "text/javascript", :src  => "jquery-1.8.2.js"}
+    :javascript
+      function display(element,uri) {
+        $(element).html("<img src=\"/spinning-wait-icons/wait30trans.gif\" alt=\"Searching PubChem\">");
+        $.ajax({
+          url: uri,
+          success: function(data){
+            $(element).html(data);
+          },
+          error: function(data,textStatus,message){
+            $(element).html(message);
+          }
+        });
+      }
+
+  %body
+    %h1 adverse outcome pathways
+    %form{:name => "form", :action => '/search', :method => "GET"}
+      %fieldset
+        %label{:for => 'identifier'} Compound name:
+        %input{:type => 'text', :name => 'name', :id => 'name', :size => '60'}
+        %input{ :type => "submit", :value => "Predict" }
+    = yield
diff --git a/views/neighbors.haml b/views/neighbors.haml
new file mode 100644
index 0000000..54905ce
--- /dev/null
+++ b/views/neighbors.haml
@@ -0,0 +1,43 @@
+%script{:type => "text/javascript", :src  => "sorttable.js"}
+%table{:class => "sortable"}
+  - session[:compound].neighbors[0..10].each do |compound|
+    %tr
+      %td{:valign => "top"}
+        %img{:src => compound.image_uri}
+      %td{:id => "sim#{compound.cid}", :valign => "top"}
+        %img{:src => "/spinning-wait-icons/wait30trans.gif"}
+        :javascript
+          $.ajax({
+            url: "/cid/#{session[:compound].cid}/cosine/#{compound.cid}",
+            success: function(data){
+              $("#sim#{compound.cid}").html(data);
+            },
+            error: function(data,textStatus,message){
+              $("#sim#{compound.cid}").html(message);
+            }
+          });
+      %td{:id => "targets#{compound.cid}", :valign => "top"}
+        %img{:src => "/spinning-wait-icons/wait30trans.gif"}
+        :javascript
+          $.ajax({
+            url: "/cid/#{compound.cid}/targets",
+            success: function(data){
+              $("#targets#{compound.cid}").html(data);
+            },
+            error: function(data,textStatus,message){
+              $("#targets#{compound.cid}").html(message);
+            }
+          });
+      %td{:id => "assays#{compound.cid}", :valign => "top"}
+        %img{:src => "/spinning-wait-icons/wait30trans.gif"}
+        :javascript
+          $.ajax({
+            url: "/cid/#{compound.cid}/other_active_assays",
+            success: function(data){
+              $("#assays#{compound.cid}").html(data);
+            },
+            error: function(data,textStatus,message){
+              $("#assays#{compound.cid}").html(message);
+            }
+          });
+      %td
diff --git a/views/predicted_assays.haml b/views/predicted_assays.haml
new file mode 100644
index 0000000..e995842
--- /dev/null
+++ b/views/predicted_assays.haml
@@ -0,0 +1,6 @@
+%ul
+  - @assays.each do |assay|
+    %li
+      %a{:href => "/aid/#{assay["AID"]}"} #{assay['Assay Name']}
+      AID:
+      = assay["AID"]
diff --git a/views/predicted_targets.haml b/views/predicted_targets.haml
new file mode 100644
index 0000000..1a172ff
--- /dev/null
+++ b/views/predicted_targets.haml
@@ -0,0 +1,6 @@
+%ul
+  - @assays.each do |assay|
+    %li
+      %a{:href => "/aid/#{assay["AID"]}"} #{assay['Target Name']}
+      Target GI:
+      = assay['Target GI']
diff --git a/views/select.haml b/views/select.haml
new file mode 100644
index 0000000..d6e3d20
--- /dev/null
+++ b/views/select.haml
@@ -0,0 +1,8 @@
+%p
+  More than one compound found for
+  = "\"#{params[:name]}\"."
+  Please select a structure:
+- @compounds.each do |compound|
+  %a{:href => "/cid/#{compound.cid}"}
+    %img{:src => compound.image_uri }
+
diff --git a/views/targets.haml b/views/targets.haml
new file mode 100644
index 0000000..1a172ff
--- /dev/null
+++ b/views/targets.haml
@@ -0,0 +1,6 @@
+%ul
+  - @assays.each do |assay|
+    %li
+      %a{:href => "/aid/#{assay["AID"]}"} #{assay['Target Name']}
+      Target GI:
+      = assay['Target GI']
-- 
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