From 61a0b59a491bbb26192050a1049e7f80998f125c Mon Sep 17 00:00:00 2001
From: Christoph Helma <helma@in-silico.ch>
Date: Tue, 12 Sep 2017 15:46:46 +0200
Subject: initial commit

---
 lib/kazius-alerts.rb   | 109 +++++++++++++++++++++++++++++++++++++++++++++++++
 lib/kazius-alerts.rb~  |  99 ++++++++++++++++++++++++++++++++++++++++++++
 test/kazius-alerts.rb  |  17 ++++++++
 test/kazius-alerts.rb~ |  15 +++++++
 4 files changed, 240 insertions(+)
 create mode 100644 lib/kazius-alerts.rb
 create mode 100644 lib/kazius-alerts.rb~
 create mode 100644 test/kazius-alerts.rb
 create mode 100644 test/kazius-alerts.rb~

diff --git a/lib/kazius-alerts.rb b/lib/kazius-alerts.rb
new file mode 100644
index 0000000..2068b34
--- /dev/null
+++ b/lib/kazius-alerts.rb
@@ -0,0 +1,109 @@
+re 'openbabel'
+
+class KaziusAlerts
+
+  SMARTS = [ # name, smarts, excluded smarts
+    ["specific arom nitro", 'O=N(~O)a', 'O=N(O)c[$(aS(=O)=O),$(aaS(=O)=O),$(aaaS(=O)=O),$(aC((F)F)F),$(aaC((F)F)F),$(aaaC((F)F)F)]'],
+    ["specific arom amine", 'a[NH2]', '[NH2]a[$(a[$(C((F)F)F),$(S(=O)=O),$(C(=O)O)]),$(aa[$(C((F)F)F),$(S(=O)=O),$(C(=O)O)]),$(aaa[$(C((F)F)F),$(S(=O)=O),$(C(=O)O)])]'],
+    ["aromatic nitroso", 'a[N;X2]=O'],
+    ["alkyl nitrite", 'CO[N;X2]=O'],
+    ["nitrosamine", 'N[N;X2]=O'],
+    ["epoxide", 'O1[c,C]-[c,C]1'],
+    ["aziridine", 'C1NC1'],
+    ["azide", 'N=[N+]=[N-]'],
+    ["diazo", 'C=[N+]=[N-]'],
+    ["triazene", 'N=N-N'],
+    ["aromatic azo", 'c[N;X2]!@;=[N,X2]c', '[$([N;X2]([$(acS((=O)=O)),$(aacS((=O)=O)),$(aaacS((=O)=O)),$(aaaacS((=O)=O))])=[N;X2][$(acS((=O)=O)),$(aacS((=O)=O)),$(aaacS((=O)=O)),$(aaaacS((=O)=O))])]'],
+    ["unsubstituted heteroatom-bonded heteroatom", '[OH,NH2][N,O]', 'O=N(O)[O-]'],
+    ["aromatic", '[OH]Na'],
+    ["aliphatic halide", '[Cl,Br,I]C'],
+    ["carboxylic acid halide", '[Cl,Br,I]C=O'],
+    ["nitrogen or sulphur mustard", '[N,S]!@[C;X4]!@[CH2][Cl,Br,I]'],
+    ["bay region in PAHs", '[cH]1[cH]ccc2c1c3c(cc2)cc[cH][cH]3'],
+    ["k-region in PAHs", '[cH]1cccc2c1[cH][cH]c3c2ccc[cH]3'],
+    ["polycyclic aromatic system", '[$(a13~a~a~a~a2~a1~a(~a~a~a3)~a~a~a2),$(a1~a~a~a2~a1~a~a3~a(~a2)~a~a~a3),$(a1~a~a~a2~a1~a~a~a3~a2~a~a~a3),$(a1~a~a~a~a2~a1~a3~a(~a2)~a~a~a~a3),$(a1~a~a~a~a2~a1~a~a3~a(~a2)~a~a~a3),$(a1~a~a~a~a2~a1~a~a3~a(~a2)~a~a~a~a3),$(a1~a~a~a~a2~a1~a~a~a3~a2~a~a~a3),$(a1~a~a~a~a2~a1~a~a~a3~a2~a~a~a~a3),$(a13~a~a~a~a2~a1~a(~a~a~a3)~a~a2)]'], # smarts error of original smarts fixed
+    ["sulphonate bonded carbon", '[$([C,c]OS((=O)=O)O!@[c,C]),$([c,C]S((=O)=O)O!@[c,C])]'],
+    ["aliphatic N-nitro", 'O=N(~O)N'],
+    ["alpha,beta unsaturated aldehyde", '[$(O=[CH]C=C),$(O=[CH]C=O)]', '[$(O=[CH]C([N,O,S])=C),$(O=[CH]C=C[N,O,S]),$(O=[CH]C=Ca)]'],
+    ["diazonium", '[N;v4]#N'],
+    ["beta-propriolactone", 'O=C1CCO1'],
+    ["alpha,beta unsaturated alkoxy group", '[CH]=[CH]O'],
+    ["1-aryl-2-monoalkyl hydrazine", '[NH;!R][NH;!R]a'],
+    ["aromatic methylamine", '[CH3][NH]a', '[CH3][NH]a[$(a[$(C((F)F)F),$(S=O),$(C(=O)O)]),$(aa[$(C((F)F)F),$(S=O),$(C(=O)O)]),$(aaa[$(C((F)F)F),$(S=O),$(C(=O)O)])]'],
+    ["ester derivative of aromatic hydroxylamine", 'aN([$([OH]),$(O*=O)])[$([#1]),$(C(=O)[CH3]),$([CH3]),$([OH]),$(O*=O)]'],
+    ["polycyclic planar system", '[$([X2,X3]13~[X2,X3]~[X2,X3]~[X2,X3]~[X2,X3]2~[X2,X3]1~[X2,X3
+](~[X2,X3]~[X2,X3]~[X2,X3]3)~[X2,X3]~[X2,X3]~[X2,X3]2),$([X2,X3]1~[X2,X3]~[X2,X3]~[X2,X3]2~[X2,
+X3]1~[X2,X3]~[X2,X3]3~[X2,X3](~[X2,X3]2)~[X2,X3]~[X2,X3]~[X2,X3]3),$([X2,X3]1~[X2,X3]~[X2,X3]~[
+X2,X3]2~[X2,X3]1~[X2,X3]~[X2,X3]~[X2,X3]3~[X2,X3]2~[X2,X3]~[X2,X3]~[X2,X3]3),$([X2,X3]1~[X2,X3]
+~[X2,X3]~[X2,X3]~[X2,X3]2~[X2,X3]1~[X2,X3]3~[X2,X3](~[X2,X3]2)~[X2,X3]~[X2,X3]~[X2,X3]~[X2,X3]3),$([X2,X3]1~[X2,X3]~[X2,X3]~[X2,X3]~[X2,X3]2~[X2,X3]1~[X2,X3]~[X2,X3]3~[X2,X3](~[X2,X3]2)~[X2,X3]~[X2,X3]~[X2,X3]3),$([X2,X3]1~[X2,X3]~[X2,X3]~[X2,X3]~[X2,X3]2~[X2,X3]1~[X2,X3]~[X2,X3]3~[X2,X3](~[X2,X3]2)~[X2,X3]~[X2,X3]~[X2,X3]~[X2,X3]3),$([X2,X3]1~[X2,X3]~[X2,X3]~[X2,X3]~[X2,X3]2~[X2,X3]1~[X2,X3]~[X2,X3]~[X2,X3]3~[X2,X3]2~[X2,X3]~[X2,X3]~[X2,X3]3),$([X2,X3]1~[X2,X3]~[X2,X3]~[X2,X3]~[X2,X3]2~[X2,X3]1~[X2,X3]~[X2,X3]~[X2,X3]3~[X2,X3]2~[X2,X3]~[X2,X3]~[X2,X3]~[X2,X3]3),$([X2,X3]13~[X2,X3]~[X2,X3]~[X2,X3]~[X2,X3]2~[X2,X3]1~[X2,X3](~[X2,X3]~[X2,X3]~[X2,X3]3)~[X2,X3]~[X2,X3]2)]', '[S]1-*~*-[N,O,S]-*~*-1'] # smarts error of original smarts fixed
+  ]
+
+  CONFIDENCES = {
+    "specific arom nitro" => 0.81,
+    "specific arom amine" => 0.79,
+    "nitrosamine" => 0.90,
+    "epoxide" => 0.85,
+    "aliphatic halide" => 0.79,
+    "polycyclic aromatic system" => 0.90,
+    "other SAs" => 0.81
+  }
+
+  def self.predict smiles
+    smi2mol = OpenBabel::OBConversion.new
+    smi2mol.set_in_format("smi")
+    mol = OpenBabel::OBMol.new
+    smi2mol.read_string(mol, smiles)
+
+    matches = []
+    prediction = false
+    error_product = 1
+
+    smarts_pattern = OpenBabel::OBSmartsPattern.new
+    SMARTS.each do |sma|
+      if sma[2]
+        smarts_pattern.init sma[1]
+        if smarts_pattern.match(mol)
+          smarts_pattern.init sma[2]
+          matches << sma if !smarts_pattern.match(mol)
+        end
+      else
+        smarts_pattern.init sma[1]
+        matches << sma if smarts_pattern.match(mol)
+      end
+
+    matches.each { |m| error_product *= error(m) }
+
+    prediction = true if matches.size > 0
+    {:prediction => prediction, :error_product => error_product, :matches => matches}
+  end
+
+  def self.error(alert)
+    if CONFIDENCES[alert[0]]
+      return 1 - CONFIDENCES[alert[0]]
+    else
+      return 1 - CONFIDENCES["other SAs"]
+    end
+  end
+
+end
+
+class ConsensusMutagenicity
+
+  def self.predict smiles
+    sa_prediction = KaziusAlerts.predict smiles
+    lazar_prediction = Lazar.predict smiles
+    confidence = 0
+    if sa_prediction[:prediction] == false && lazar_mutagenicity.prediction == 0
+      confidence = 0.85
+    elsif sa_prediction[:prediction] == true && lazar_mutagenicity.prediction == 1
+      confidence = 0.85 * ( 1 - sa_prediction[:error_product] )
+    elsif sa_prediction[:prediction] == false && lazar_mutagenicity.prediction == 1
+      confidence = 0.11
+    elsif sa_prediction[:prediction] == true && lazar_mutagenicity.prediction == 0
+      confidence = ( 1 - sa_prediction[:error_product] ) - 0.57
+    end
+    {:prediction => prediction, :confidence => confidence}
+  end
+
+end
+
diff --git a/lib/kazius-alerts.rb~ b/lib/kazius-alerts.rb~
new file mode 100644
index 0000000..ccc888c
--- /dev/null
+++ b/lib/kazius-alerts.rb~
@@ -0,0 +1,99 @@
+require 'openbabel'
+
+class KaziusAlerts
+
+  SMARTS = [ # name, smarts, excluded smarts
+    ["specific arom nitro", 'O=N(~O)a', 'O=N(O)c[$(aS(=O)=O),$(aaS(=O)=O),$(aaaS(=O)=O),$(aC((F)F)F),$(aaC((F)F)F),$(aaaC((F)F)F)]'],
+    ["specific arom amine", 'a[NH2]', '[NH2]a[$(a[$(C((F)F)F),$(S(=O)=O),$(C(=O)O)]),$(aa[$(C((F)F)F),$(S(=O)=O),$(C(=O)O)]),$(aaa[$(C((F)F)F),$(S(=O)=O),$(C(=O)O)])]'],
+    ["aromatic nitroso", 'a[N;X2]=O'],
+    ["alkyl nitrite", 'CO[N;X2]=O'],
+    ["nitrosamine", 'N[N;X2]=O'],
+    ["epoxide", 'O1[c,C]-[c,C]1'],
+    ["aziridine", 'C1NC1'],
+    ["azide", 'N=[N+]=[N-]'],
+    ["diazo", 'C=[N+]=[N-]'],
+    ["triazene", 'N=N-N'],
+    ["aromatic azo", 'c[N;X2]!@;=[N,X2]c', '[$([N;X2]([$(acS((=O)=O)),$(aacS((=O)=O)),$(aaacS((=O)=O)),$(aaaacS((=O)=O))])=[N;X2][$(acS((=O)=O)),$(aacS((=O)=O)),$(aaacS((=O)=O)),$(aaaacS((=O)=O))])]'],
+    ["unsubstituted heteroatom-bonded heteroatom", '[OH,NH2][N,O]', 'O=N(O)[O-]'],
+    ["aromatic", '[OH]Na'],
+    ["aliphatic halide", '[Cl,Br,I]C'],
+    ["carboxylic acid halide", '[Cl,Br,I]C=O'],
+    ["nitrogen or sulphur mustard", '[N,S]!@[C;X4]!@[CH2][Cl,Br,I]'],
+    ["bay region in PAHs", '[cH]1[cH]ccc2c1c3c(cc2)cc[cH][cH]3'],
+    ["k-region in PAHs", '[cH]1cccc2c1[cH][cH]c3c2ccc[cH]3'],
+    ["polycyclic aromatic system", '[$(a13~a~a~a~a2~a1~a(~a~a~a3)~a~a~a2),$(a1~a~a~a2~a1~a~a3~a(~a2)~a~a~a3),$(a1~a~a~a2~a1~a~a~a3~a2~a~a~a3),$(a1~a~a~a~a2~a1~a3~a(~a2)~a~a~a~a3),$(a1~a~a~a~a2~a1~a~a3~a(~a2)~a~a~a3),$(a1~a~a~a~a2~a1~a~a3~a(~a2)~a~a~a~a3),$(a1~a~a~a~a2~a1~a~a~a3~a2~a~a~a3),$(a1~a~a~a~a2~a1~a~a~a3~a2~a~a~a~a3),$(a13~a~a~a~a2~a1~a(~a~a~a3)~a~a2)]'], # smarts error of original smarts fixed
+    ["sulphonate bonded carbon", '[$([C,c]OS((=O)=O)O!@[c,C]),$([c,C]S((=O)=O)O!@[c,C])]'],
+    ["aliphatic N-nitro", 'O=N(~O)N'],
+    ["alpha,beta unsaturated aldehyde", '[$(O=[CH]C=C),$(O=[CH]C=O)]', '[$(O=[CH]C([N,O,S])=C),$(O=[CH]C=C[N,O,S]),$(O=[CH]C=Ca)]'],
+    ["diazonium", '[N;v4]#N'],
+    ["beta-propriolactone", 'O=C1CCO1'],
+    ["alpha,beta unsaturated alkoxy group", '[CH]=[CH]O'],
+    ["1-aryl-2-monoalkyl hydrazine", '[NH;!R][NH;!R]a'],
+    ["aromatic methylamine", '[CH3][NH]a', '[CH3][NH]a[$(a[$(C((F)F)F),$(S=O),$(C(=O)O)]),$(aa[$(C((F)F)F),$(S=O),$(C(=O)O)]),$(aaa[$(C((F)F)F),$(S=O),$(C(=O)O)])]'],
+    ["ester derivative of aromatic hydroxylamine", 'aN([$([OH]),$(O*=O)])[$([#1]),$(C(=O)[CH3]),$([CH3]),$([OH]),$(O*=O)]'],
+    ["polycyclic planar system", '[$([X2,X3]13~[X2,X3]~[X2,X3]~[X2,X3]~[X2,X3]2~[X2,X3]1~[X2,X3](~[X2,X3]~[X2,X3]~[X2,X3]3)~[X2,X3]~[X2,X3]~[X2,X3]2),$([X2,X3]1~[X2,X3]~[X2,X3]~[X2,X3]2~[X2,X3]1~[X2,X3]~[X2,X3]3~[X2,X3](~[X2,X3]2)~[X2,X3]~[X2,X3]~[X2,X3]3),$([X2,X3]1~[X2,X3]~[X2,X3]~[X2,X3]2~[X2,X3]1~[X2,X3]~[X2,X3]~[X2,X3]3~[X2,X3]2~[X2,X3]~[X2,X3]~[X2,X3]3),$([X2,X3]1~[X2,X3]~[X2,X3]~[X2,X3]~[X2,X3]2~[X2,X3]1~[X2,X3]3~[X2,X3](~[X2,X3]2)~[X2,X3]~[X2,X3]~[X2,X3]~[X2,X3]3),$([X2,X3]1~[X2,X3]~[X2,X3]~[X2,X3]~[X2,X3]2~[X2,X3]1~[X2,X3]~[X2,X3]3~[X2,X3](~[X2,X3]2)~[X2,X3]~[X2,X3]~[X2,X3]3),$([X2,X3]1~[X2,X3]~[X2,X3]~[X2,X3]~[X2,X3]2~[X2,X3]1~[X2,X3]~[X2,X3]3~[X2,X3](~[X2,X3]2)~[X2,X3]~[X2,X3]~[X2,X3]~[X2,X3]3),$([X2,X3]1~[X2,X3]~[X2,X3]~[X2,X3]~[X2,X3]2~[X2,X3]1~[X2,X3]~[X2,X3]~[X2,X3]3~[X2,X3]2~[X2,X3]~[X2,X3]~[X2,X3]3),$([X2,X3]1~[X2,X3]~[X2,X3]~[X2,X3]~[X2,X3]2~[X2,X3]1~[X2,X3]~[X2,X3]~[X2,X3]3~[X2,X3]2~[X2,X3]~[X2,X3]~[X2,X3]~[X2,X3]3),$([X2,X3]13~[X2,X3]~[X2,X3]~[X2,X3]~[X2,X3]2~[X2,X3]1~[X2,X3](~[X2,X3]~[X2,X3]~[X2,X3]3)~[X2,X3]~[X2,X3]2)]', '[S]1-*~*-[N,O,S]-*~*-1'] # smarts error of original smarts fixed
+  ]
+
+  CONFIDENCES = {
+    "specific arom nitro" => 0.81,
+    "specific arom amine" => 0.79,
+    "nitrosamine" => 0.90,
+    "epoxide" => 0.85,
+    "aliphatic halide" => 0.79,
+    "polycyclic aromatic system" => 0.90,
+    "other SAs" => 0.81
+  }
+
+  def self.predict smiles
+    smi2mol = OBConversion.new
+    smi2mol.set_in_format("smi")
+    mol = OBMol.new
+    smi2mol.read_string(mol, smiles)
+
+    matches = []
+    prediction = false
+    error_product = 1
+
+    SMARTS.each do |sma|
+      if sma[2]
+        matches << sma if mol.matches_smarts?(sma[1]) && !mol.matches_smarts?(sma[2])
+      else
+        matches << sma if mol.matches_smarts?(sma[1])
+      end
+    end
+
+    matches.each { |m| error_product *= error(m) }
+
+    prediction = true if matches.size > 0
+    {:prediction => prediction, :error_product => error_product, :matches => matches}
+  end
+
+  def self.error(alert)
+    if CONFIDENCES[alert[0]]
+      return 1 - CONFIDENCES[alert[0]]
+    else
+      return 1 - CONFIDENCES["other SAs"]
+    end
+  end
+
+end
+
+class ConsensusMutagenicity
+
+  def self.predict smiles
+    sa_prediction = KaziusAlerts.predict smiles
+    lazar_prediction = Lazar.predict smiles
+    confidence = 0
+    if sa_prediction[:prediction] == false && lazar_mutagenicity.prediction == 0
+      confidence = 0.85
+    elsif sa_prediction[:prediction] == true && lazar_mutagenicity.prediction == 1
+      confidence = 0.85 * ( 1 - sa_prediction[:error_product] )
+    elsif sa_prediction[:prediction] == false && lazar_mutagenicity.prediction == 1
+      confidence = 0.11
+    elsif sa_prediction[:prediction] == true && lazar_mutagenicity.prediction == 0
+      confidence = ( 1 - sa_prediction[:error_product] ) - 0.57
+    end
+    {:prediction => prediction, :confidence => confidence}
+  end
+
+end
diff --git a/test/kazius-alerts.rb b/test/kazius-alerts.rb
new file mode 100644
index 0000000..ac2f098
--- /dev/null
+++ b/test/kazius-alerts.rb
@@ -0,0 +1,17 @@
+require 'minitest/autorun'
+#require 'kazius-alerts'
+require_relative '../lib/kazius-alerts.rb'
+
+class KaziusAlertsTest < MiniTest::Test
+
+  def test_alerts_size
+    assert_equal 29, KaziusAlerts::SMARTS.size
+  end
+
+  def test_kazius_alerts_prediction
+    prediction = KaziusAlerts.predict("c1ccccc1NN")
+    assert prediction[:prediction]
+    assert_equal [["unsubstituted heteroatom-bonded heteroatom", "[OH,NH2][N,O]", "O=N(O)[O-]"]], prediction[:matches]
+  end
+
+end
diff --git a/test/kazius-alerts.rb~ b/test/kazius-alerts.rb~
new file mode 100644
index 0000000..e0e0acf
--- /dev/null
+++ b/test/kazius-alerts.rb~
@@ -0,0 +1,15 @@
+require 'minitest/autorun'
+#require 'kazius-alerts'
+require_relative '../lib/kazius-alerts.rb'
+
+class KaziusAlertsTest < MiniTest::Test
+
+  def test_alerts_size
+    assert_equal 29, KaziusAlerts::SMARTS.size
+  end
+
+  def test_kazius_alerts_prediction
+    assert_equal 29, KaziusAlerts::SMARTS.size
+  end
+
+end
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