summaryrefslogtreecommitdiff
path: root/lib/compound.rb
blob: e8f6bc47b973a76cb2ef279b80a1b1738abab981 (plain)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
CACTUS_URI="https://cactus.nci.nih.gov/chemical/structure/"

module OpenTox

  # Small molecules with defined chemical structures
  class Compound < Substance
    require_relative "unique_descriptors.rb"
    DEFAULT_FINGERPRINT = "MP2D"

    field :inchi, type: String
    field :smiles, type: String
    field :inchikey, type: String
    field :names, type: Array
    field :cid, type: String
    field :chemblid, type: String
    field :png_id, type: BSON::ObjectId
    field :svg_id, type: BSON::ObjectId
    field :sdf_id, type: BSON::ObjectId
    field :fingerprints, type: Hash, default: {}
    field :default_fingerprint_size, type: Integer

    index({smiles: 1}, {unique: true})

    # Overwrites standard Mongoid method to create fingerprints before database insertion
    def self.find_or_create_by params
      compound = self.find_or_initialize_by params
      compound.default_fingerprint_size = compound.fingerprint(DEFAULT_FINGERPRINT).size
      compound.save
      compound
    end

    # Create chemical fingerprint
    # @param [String] fingerprint type
    # @return [Array<String>] 
    def fingerprint type=DEFAULT_FINGERPRINT
      unless fingerprints[type]
        return [] unless self.smiles
        #http://openbabel.org/docs/dev/FileFormats/MolPrint2D_format.html#molprint2d-format
        if type == "MP2D"
          fp = obconversion(smiles,"smi","mpd").strip.split("\t")
          name = fp.shift # remove Title
          fingerprints[type] = fp.uniq # no fingerprint counts
        #http://openbabel.org/docs/dev/FileFormats/Multilevel_Neighborhoods_of_Atoms_(MNA).html
        elsif type== "MNA"
          level = 2 # TODO: level as parameter, evaluate level 1, see paper
          fp = obconversion(smiles,"smi","mna","xL\"#{level}\"").split("\n")
          fp.shift # remove Title
          fingerprints[type] = fp
        else # standard fingerprints
          fp = OpenBabel::OBFingerprint.find_fingerprint(type)
          obmol = OpenBabel::OBMol.new
          obconversion = OpenBabel::OBConversion.new
          obconversion.set_in_format "smi"
          obconversion.read_string obmol, self.smiles
          result = OpenBabel::VectorUnsignedInt.new
          fp.get_fingerprint(obmol,result)
          # TODO: %ignore *::DescribeBits @ line 163 openbabel/scripts/openbabel-ruby.i
          #p OpenBabel::OBFingerprint.describe_bits(result)
          # convert result to a list of the bits that are set
          # from openbabel/scripts/python/pybel.py line 830
          # see also http://openbabel.org/docs/dev/UseTheLibrary/Python_Pybel.html#fingerprints
          result = result.to_a
          bitsperint = OpenBabel::OBFingerprint.getbitsperint()
          bits_set = []
          start = 1
          result.each do |x|
            i = start
            while x > 0 do
              bits_set << i if (x % 2) == 1
              x >>= 1
              i += 1
            end
            start += bitsperint
          end
          fingerprints[type] = bits_set
        end
        save
      end
      fingerprints[type]
    end

    # Calculate physchem properties
    # @param [Array<Hash>] list of descriptors
    # @return [Array<Float>]
    def calculate_properties descriptors=PhysChem::OPENBABEL
      calculated_ids = properties.keys
      # BSON::ObjectId instances are not allowed as keys in a BSON document.
      new_ids = descriptors.collect{|d| d.id.to_s} - calculated_ids
      descs = {}
      algos = {}
      new_ids.each do |id|
        descriptor = PhysChem.find id
        descs[[descriptor.library, descriptor.descriptor]]  = descriptor
        algos[descriptor.name] = descriptor
      end
      # avoid recalculating Cdk features with multiple values
      descs.keys.uniq.each do |k|
        descs[k].send(k[0].downcase,k[1],self).each do |n,v|
          properties[algos[n].id.to_s] = v # BSON::ObjectId instances are not allowed as keys in a BSON document.
        end
      end
      save
      descriptors.collect{|d| properties[d.id.to_s]}
    end

    # Match a SMARTS substructure
    # @param [String] smarts
    # @param [TrueClass,FalseClass] count matches or return true/false
    # @return [TrueClass,FalseClass,Fixnum] 
    def smarts_match smarts, count=false
      obconversion = OpenBabel::OBConversion.new
      obmol = OpenBabel::OBMol.new
      obconversion.set_in_format('smi')
      obconversion.read_string(obmol,self.smiles)
      smarts_pattern = OpenBabel::OBSmartsPattern.new
      smarts.collect do |sma|
        smarts_pattern.init(sma.smarts)
        if smarts_pattern.match(obmol)
          count ? value = smarts_pattern.get_map_list.to_a.size : value = 1
        else
          value = 0 
        end
        value
      end
    end

    # Create a compound from smiles string
    # @example
    #   compound = OpenTox::Compound.from_smiles("c1ccccc1")
    # @param [String] smiles 
    # @return [OpenTox::Compound]
    def self.from_smiles smiles
      if smiles.match(/\s/) # spaces seem to confuse obconversion and may lead to invalid smiles
        warn "SMILES parsing failed for '#{smiles}'', SMILES string contains whitespaces."
        return nil
      end
      smiles = obconversion(smiles,"smi","can") # test if SMILES is correct and return canonical smiles (for compound comparisons)
      if smiles.empty?
        warn "SMILES parsing failed for '#{smiles}'', this may be caused by an incorrect SMILES string."
        return nil
      else
        Compound.find_or_create_by :smiles => smiles 
      end
    end

    # Create a compound from InChI string
    # @param [String] InChI 
    # @return [OpenTox::Compound] 
    def self.from_inchi inchi
      #smiles = `echo "#{inchi}" | "#{File.join(File.dirname(__FILE__),"..","openbabel","bin","babel")}" -iinchi - -ocan`.chomp.strip
      smiles = obconversion(inchi,"inchi","can")
      if smiles.empty?
        Compound.find_or_create_by(:warnings => ["InChi parsing failed for #{inchi}, this may be caused by an incorrect InChi string or a bug in OpenBabel libraries."])
      else
        Compound.find_or_create_by(:smiles => smiles, :inchi => inchi)
      end
    end

    # Create a compound from SDF 
    # @param [String] SDF 
    # @return [OpenTox::Compound] 
    def self.from_sdf sdf
      # do not store sdf because it might be 2D
      Compound.from_smiles obconversion(sdf,"sdf","can")
    end

    # Create a compound from name. Relies on an external service for name lookups.
    # @example
    #   compound = OpenTox::Compound.from_name("Benzene")
    # @param [String] name, can be also an InChI/InChiKey, CAS number, etc
    # @return [OpenTox::Compound]
    def self.from_name name
      Compound.from_smiles RestClientWrapper.get(File.join(CACTUS_URI,URI.escape(name),"smiles"))
    end

    # Get InChI
    # @return [String] 
    def inchi
      unless self["inchi"]
        result = obconversion(smiles,"smi","inchi")
        update(:inchi => result.chomp) if result and !result.empty?
      end
      self["inchi"]
    end

    # Get InChIKey
    # @return [String]
    def inchikey
      update(:inchikey => obconversion(smiles,"smi","inchikey")) unless self["inchikey"]
      self["inchikey"]
    end

    # Get (canonical) smiles
    # @return [String]
    def smiles
      update(:smiles => obconversion(self["smiles"],"smi","can")) unless self["smiles"] 
      self["smiles"]
    end

    # Get SDF
    # @return [String]
    def sdf
      if self.sdf_id.nil? 
        sdf = obconversion(smiles,"smi","sdf")
        file = Mongo::Grid::File.new(sdf, :filename => "#{id}.sdf",:content_type => "chemical/x-mdl-sdfile")
        sdf_id = $gridfs.insert_one file
        update :sdf_id => sdf_id
      end
      $gridfs.find_one(_id: self.sdf_id).data
    end

    # Get SVG image
    # @return [image/svg] Image data
    def svg
      if self.svg_id.nil?
       svg = obconversion(smiles,"smi","svg")
       file = Mongo::Grid::File.new(svg, :filename => "#{id}.svg", :content_type => "image/svg")
       update(:svg_id => $gridfs.insert_one(file))
      end
      $gridfs.find_one(_id: self.svg_id).data
    end

    # Get png image
    # @example
    #   image = compound.png
    # @return [image/png] Image data
    def png
      if self.png_id.nil?
       png = obconversion(smiles,"smi","_png2")
       file = Mongo::Grid::File.new(Base64.encode64(png), :filename => "#{id}.png", :content_type => "image/png")
       update(:png_id => $gridfs.insert_one(file))
      end
      Base64.decode64($gridfs.find_one(_id: self.png_id).data)
    end

    # Get all known compound names. Relies on an external service for name lookups.
    # @example
    #   names = compound.names
    # @return [Array<String>] 
    def names
      update(:names => RestClientWrapper.get("#{CACTUS_URI}#{inchi}/names").split("\n")) unless self["names"] 
      self["names"]
    end

    # Get PubChem Compound Identifier (CID), obtained via REST call to PubChem
    # @return [String] 
    def cid
      pug_uri = "https://pubchem.ncbi.nlm.nih.gov/rest/pug/"
      update(:cid => RestClientWrapper.post(File.join(pug_uri, "compound", "inchi", "cids", "TXT"),{:inchi => inchi}).strip) unless self["cid"] 
      self["cid"]
    end

    # Get ChEMBL database compound id, obtained via REST call to ChEMBL
    # @return [String] 
    def chemblid
      # https://www.ebi.ac.uk/chembldb/ws#individualCompoundByInChiKey
      uri = "https://www.ebi.ac.uk/chemblws/compounds/smiles/#{smiles}.json"
      update(:chemblid => JSON.parse(RestClientWrapper.get(uri))["compounds"].first["chemblId"]) unless self["chemblid"] 
      self["chemblid"]
    end

    def db_neighbors min_sim: 0.2, dataset_id:
      #p fingerprints[DEFAULT_FINGERPRINT]
      # from http://blog.matt-swain.com/post/87093745652/chemical-similarity-search-in-mongodb

      #qn = default_fingerprint_size
      #qmin = qn * threshold
      #qmax = qn / threshold
      #not sure if it is worth the effort of keeping feature counts up to date (compound deletions, additions, ...)
      #reqbits = [count['_id'] for count in db.mfp_counts.find({'_id': {'$in': qfp}}).sort('count', 1).limit(qn - qmin + 1)]
      aggregate = [
        #{'$match': {'mfp.count': {'$gte': qmin, '$lte': qmax}, 'mfp.bits': {'$in': reqbits}}},
        #{'$match' =>  {'_id' => {'$ne' => self.id}}}, # remove self
        {'$project' => {
          'similarity' => {'$let' => {
            'vars' => {'common' => {'$size' => {'$setIntersection' => ["$fingerprints.#{DEFAULT_FINGERPRINT}", fingerprints[DEFAULT_FINGERPRINT]]}}},
            'in' => {'$divide' => ['$$common', {'$subtract' => [{'$add' => [default_fingerprint_size, '$default_fingerprint_size']}, '$$common']}]}
          }},
          '_id' => 1,
          #'measurements' => 1,
          'dataset_ids' => 1
        }},
        {'$match' =>  {'similarity' => {'$gte' => min_sim}}},
        {'$sort' => {'similarity' => -1}}
      ]

      # TODO move into aggregate pipeline, see http://stackoverflow.com/questions/30537317/mongodb-aggregation-match-if-value-in-array
      $mongo["substances"].aggregate(aggregate).select{|r| r["dataset_ids"].include? dataset_id}
        
    end
    
    # Convert mmol to mg
    # @return [Float] value in mg
    def mmol_to_mg mmol
      mmol.to_f*molecular_weight
    end

    # Convert mg to mmol
    # @return [Float] value in mmol
    def mg_to_mmol mg
      mg.to_f/molecular_weight
    end
    
    # Calculate molecular weight of Compound with OB and store it in compound object
    # @return [Float] molecular weight
    def molecular_weight
      mw_feature = PhysChem.find_or_create_by(:name => "Openbabel.MW")
      calculate_properties([mw_feature]).first
    end

    private

    def self.obconversion(identifier,input_format,output_format,option=nil)
      obconversion = OpenBabel::OBConversion.new
      obconversion.set_options(option, OpenBabel::OBConversion::OUTOPTIONS) if option
      obmol = OpenBabel::OBMol.new
      obconversion.set_in_and_out_formats input_format, output_format
      return nil if identifier.nil?
      obconversion.read_string obmol, identifier
      case output_format
      when /smi|can|inchi/
        obconversion.write_string(obmol).gsub(/\s/,'').chomp
      when /sdf/
        # TODO: find disconnected structures
        # strip_salts
        # separate
        obmol.add_hydrogens
        builder = OpenBabel::OBBuilder.new
        builder.build(obmol)

        sdf = obconversion.write_string(obmol)
print sdf
        if sdf.match(/.nan/)
          
          warn "3D generation failed for compound #{identifier}, trying to calculate 2D structure"
          obconversion.set_options("gen2D", OpenBabel::OBConversion::GENOPTIONS)
          sdf = obconversion.write_string(obmol)
          if sdf.match(/.nan/)
            warn "2D generation failed for compound #{identifier}, rendering without coordinates."
            obconversion.remove_option("gen2D", OpenBabel::OBConversion::GENOPTIONS)
            sdf = obconversion.write_string(obmol)
          end
        end
        sdf
      else
        obconversion.write_string(obmol)
      end
    end

    def obconversion(identifier,input_format,output_format,option=nil)
      self.class.obconversion(identifier,input_format,output_format,option)
    end
  end
end