models.py 26.7 KB
Newer Older
Hervé  MENAGER's avatar
Hervé MENAGER committed
1
2
3
from __future__ import unicode_literals

from django.db import models
4
from django_pandas.managers import DataFrameManager
5
from django.db.models import Max
Hervé  MENAGER's avatar
Hervé MENAGER committed
6

7
from .ws import get_pubmed_info, get_epo_info, get_uniprot_info, get_taxonomy_info, get_go_info, get_pfam_info
8

Hervé  MENAGER's avatar
Hervé MENAGER committed
9

10
class AutoFillableModel(models.Model):
Hervé  MENAGER's avatar
Hervé MENAGER committed
11

12
13
14
15
16
17
18
19
20
21
22
23
24
    """
    AutoFillableModel makes it possible to automatically fill model fields from
    external sources in the autofill() method
    The save method allows to either include autofill or not. in autofill kwarg is
    set to True, save() will first call autofill(), otherwise it won't
    """

    class Meta:
        abstract = True

    def save(self, *args, **kwargs):
        if kwargs.get('autofill') is True:
            self.autofill()
25
26
        if 'autofill' in kwargs:
            del kwargs['autofill']
Hervé  MENAGER's avatar
Hervé MENAGER committed
27
        super(AutoFillableModel, self).save(*args, **kwargs)
28
29
30


class Bibliography(AutoFillableModel):
Hervé  MENAGER's avatar
Hervé MENAGER committed
31

Hervé  MENAGER's avatar
Hervé MENAGER committed
32
33
34
35
    """
    Bibliography data table
    """
    SOURCES = (
36
37
38
        ('PM', 'PubMed ID'),
        ('PT', 'Patent'),
        ('DO', 'DOI ID')
Hervé  MENAGER's avatar
Hervé MENAGER committed
39
    )
Hervé  MENAGER's avatar
Hervé MENAGER committed
40
41
    source = models.CharField(
        'Bibliographic type', max_length=2, choices=SOURCES, default='PM')
Hervé  MENAGER's avatar
Hervé MENAGER committed
42
43
    id_source = models.CharField('Bibliographic ID', max_length=25)
    title = models.CharField('Title', max_length=300)
44
    journal_name = models.CharField('Journal name', max_length=50, null=True)
Hervé  MENAGER's avatar
Hervé MENAGER committed
45
46
    authors_list = models.CharField('Authors list', max_length=500)
    biblio_year = models.PositiveSmallIntegerField('Year')
47
    cytotox = models.BooleanField('Cytotoxicity data', default=False)
Rachel TORCHET's avatar
Rachel TORCHET committed
48
49
50
51
    in_silico = models.BooleanField('in silico study', default=False)
    in_vitro = models.BooleanField('in vitro study', default=False)
    in_vivo = models.BooleanField('in vivo study', default=False)
    in_cellulo = models.BooleanField('in cellulo study', default=False)
Hervé  MENAGER's avatar
Hervé MENAGER committed
52
53
    pharmacokinetic = models.BooleanField(
        'pharmacokinetic study', default=False)
Rachel TORCHET's avatar
Rachel TORCHET committed
54
    xray = models.BooleanField('X-Ray data', default=False)
Hervé  MENAGER's avatar
Hervé MENAGER committed
55

56
    def autofill(self):
57
58
59
60
61
62
63
64
        if self.source == 'PM':
            info = get_pubmed_info(self.id_source)
        else:
            info = get_epo_info(self.id_source)
        self.title = info['title']
        self.journal_name = info['journal_name']
        self.authors_list = info['authors_list']
        self.biblio_year = info['biblio_year']
Hervé  MENAGER's avatar
Hervé MENAGER committed
65

Hervé  MENAGER's avatar
Hervé MENAGER committed
66
67
68
    class Meta:
        verbose_name_plural = "bibliographies"

69
70
    def __str__(self):
        return '{}, {}'.format(self.source, self.id_source)
71

Hervé  MENAGER's avatar
Hervé MENAGER committed
72

73
class Taxonomy(AutoFillableModel):
Hervé  MENAGER's avatar
Hervé MENAGER committed
74
75
    taxonomy_id = models.DecimalField(
        'NCBI TaxID', unique=True, max_digits=9, decimal_places=0)
Hervé  MENAGER's avatar
Hervé MENAGER committed
76
    name = models.CharField('Organism name', max_length=200)
77

78
    def autofill(self):
79
80
81
        info = get_taxonomy_info(self.taxonomy_id)
        self.name = info['scientific_name']

82
83
84
    def __str__(self):
        return self.name

Hervé  MENAGER's avatar
Hervé MENAGER committed
85
86
    class Meta:
        verbose_name_plural = "taxonomies"
Hervé  MENAGER's avatar
Hervé MENAGER committed
87

Hervé  MENAGER's avatar
Hervé MENAGER committed
88

89
class MolecularFunction(AutoFillableModel):
Hervé  MENAGER's avatar
Hervé MENAGER committed
90
91
    go_id = models.CharField('Gene Ontology ID', unique=True, max_length=10)
                             # GO term id format: 'GO:0000000'
Hervé  MENAGER's avatar
Hervé MENAGER committed
92
93
    description = models.CharField('description', max_length=500)

94
    def autofill(self):
95
96
97
        info = get_go_info(self.go_id)
        self.description = info['label']

98
99
100
    def __str__(self):
        return self.description

Hervé  MENAGER's avatar
Hervé MENAGER committed
101

102
class Protein(AutoFillableModel):
Hervé  MENAGER's avatar
Hervé MENAGER committed
103
    uniprot_id = models.CharField('Uniprot ID', unique=True, max_length=10)
Hervé  MENAGER's avatar
Hervé MENAGER committed
104
105
    recommended_name_long = models.CharField(
        'Uniprot Recommended Name (long)', max_length=75)
Hervé  MENAGER's avatar
Hervé MENAGER committed
106
107
108
    short_name = models.CharField('Short name', max_length=50)
    gene_name = models.CharField('Gene name', unique=True, max_length=30)
    entry_name = models.CharField('Entry name', max_length=30)
109
    organism = models.ForeignKey('Taxonomy', models.CASCADE)
Hervé  MENAGER's avatar
Hervé MENAGER committed
110
111
    molecular_functions = models.ManyToManyField(MolecularFunction)

112
    def autofill(self):
113
        info = get_uniprot_info(self.uniprot_id)
114
        self.recommended_name_long = info['recommended_name']
115
116
        self.gene_name = info['gene']
        self.entry_name = info['entry_name']
117
        self.short_name = info['short_name']
118
119
120
121
122
        try:
            taxonomy = Taxonomy.objects.get(taxonomy_id=info['organism'])
        except Taxonomy.DoesNotExist:
            taxonomy = Taxonomy()
            taxonomy.taxonomy_id = info['organism']
123
            taxonomy.save(autofill=True)
124
        self.organism = taxonomy
125
        super(Protein, self).save()
126
127
128
129
130
131
        for go_id in info['molecular_functions']:
            try:
                mol_function = MolecularFunction.objects.get(go_id=go_id)
            except MolecularFunction.DoesNotExist:
                mol_function = MolecularFunction()
                mol_function.go_id = go_id
132
                mol_function.save(autofill=True)
133
            self.molecular_functions.add(mol_function)
134

135
136
137
    def __str__(self):
        return '{} ({})'.format(self.uniprot_id, self.recommended_name_long)

Hervé  MENAGER's avatar
Hervé MENAGER committed
138

139
class Domain(AutoFillableModel):
Hervé  MENAGER's avatar
Hervé MENAGER committed
140
141
    pfam_acc = models.CharField('Pfam Accession', max_length=10, unique=True)
    pfam_id = models.CharField('Pfam Family Identifier', max_length=20)
Hervé  MENAGER's avatar
Hervé MENAGER committed
142
    pfam_description = models.CharField('Pfam Description', max_length=100)
Hervé  MENAGER's avatar
Hervé MENAGER committed
143
144
145
    domain_family = models.CharField('Domain family', max_length=25)
                                     # TODO: what is this field? check database
                                     # contents
146

147
    def autofill(self):
148
149
150
        info = get_pfam_info(self.pfam_acc)
        self.pfam_id = info['id']
        self.pfam_description = info['description']
Hervé  MENAGER's avatar
Hervé MENAGER committed
151

152
153
154
    def __str__(self):
        return '{} ({}-{})'.format(self.pfam_acc, self.pfam_id, self.pfam_description)

Hervé  MENAGER's avatar
Hervé MENAGER committed
155

156
class ProteinDomainComplex(models.Model):
157
158
    protein = models.ForeignKey('Protein', models.CASCADE)
    domain = models.ForeignKey('Domain', models.CASCADE)
Hervé  MENAGER's avatar
Hervé MENAGER committed
159
160
161
    ppc_copy_nb = models.IntegerField(
        'Number of copies of the protein in the complex')

Hervé  MENAGER's avatar
Hervé MENAGER committed
162
163
    class Meta:
        verbose_name_plural = "complexes"
164

165
166
167
    def __str__(self):
        return '{}-{}'.format(self.protein_id, self.domain_id)

168
169
    def name(self):
        return self.protein.short_name
Hervé  MENAGER's avatar
Hervé MENAGER committed
170

171

172
class ProteinDomainBoundComplex(ProteinDomainComplex):
Hervé  MENAGER's avatar
Hervé MENAGER committed
173
174
175
    ppp_copy_nb_per_p = models.IntegerField(
        'Number of copies of the protein in the pocket')

176
177
    class Meta:
        verbose_name_plural = "bound complexes"
Hervé  MENAGER's avatar
Hervé MENAGER committed
178
179


180
class ProteinDomainPartnerComplex(ProteinDomainComplex):
Hervé  MENAGER's avatar
Hervé MENAGER committed
181

182
183
    class Meta:
        verbose_name_plural = "partner complexes"
Hervé  MENAGER's avatar
Hervé MENAGER committed
184

Hervé  MENAGER's avatar
Hervé MENAGER committed
185

186
187
188
class Symmetry(models.Model):
    code = models.CharField('Symmetry code', max_length=2)
    description = models.CharField('Description', max_length=300)
Hervé  MENAGER's avatar
Hervé MENAGER committed
189

190
191
192
    class Meta:
        verbose_name_plural = "symmetries"

193
194
195
    def __str__(self):
        return '{} ({})'.format(self.code, self.description)

196
197

class Disease(models.Model):
Hervé  MENAGER's avatar
Hervé MENAGER committed
198
199
    name = models.CharField('Disease', max_length=30, unique=True)
                            # is there any database/nomenclature for diseases?
200
201
202
203

    def __str__(self):
        return self.name

Hervé  MENAGER's avatar
Hervé MENAGER committed
204
205
206
207
208
class PpiFamily(models.Model):
    name = models.CharField('Name', max_length=30, unique=True)

    def __str__(self):
        return self.name
Hervé  MENAGER's avatar
Hervé MENAGER committed
209

210
class Ppi(models.Model):
211
    pdb_id = models.CharField('PDB ID', max_length=4, null=True)
Hervé  MENAGER's avatar
Hervé MENAGER committed
212
213
    pockets_nb = models.IntegerField(
        'Total number of pockets in the complex', default=1)
214
    symmetry = models.ForeignKey(Symmetry, models.CASCADE)
215
    diseases = models.ManyToManyField(Disease)
Hervé  MENAGER's avatar
Hervé MENAGER committed
216
    family = models.ForeignKey(PpiFamily, models.CASCADE, null=True)
Hervé  MENAGER's avatar
Hervé MENAGER committed
217

218
219
220
    def __str__(self):
        return '{} PPI, PDB:{}'.format(self.symmetry.description, self.pdb_id or 'unknown')

221
222
223
224
225
226
227
228
229
230
    def get_ppi_complexes(self):
        """
        return all ppi complexes belonging to this ppi
        """
        return PpiComplex.objects.filter(ppi=self)

    def get_ppi_bound_complexes(self):
        """
        return bound ppi complexes belonging to this ppi
        """
Hervé  MENAGER's avatar
Hervé MENAGER committed
231
        # this is the less efficient query ever seen, FIXME
232
233
        return PpiComplex.objects.filter(ppi=self, complex__in=ProteinDomainBoundComplex.objects.all())

234
235
236
237
238
239
240
241
242
243
244
    @property
    def name(self):
        all_protein_names = set([ppi_complex.complex.protein.short_name for ppi_complex in self.get_ppi_complexes()])
        bound_protein_names = set([ppi_complex.complex.protein.short_name for ppi_complex in self.get_ppi_bound_complexes()])
        partner_protein_names = all_protein_names - bound_protein_names
        bound_str = ','.join(bound_protein_names)
        partner_str = ','.join(partner_protein_names)
        name = bound_str
        if partner_str!='':
            name += ' / ' + partner_str
        return name
245

Hervé  MENAGER's avatar
Hervé MENAGER committed
246
class PpiComplex(models.Model):
247
248
    ppi = models.ForeignKey(Ppi, models.CASCADE)
    complex = models.ForeignKey(ProteinDomainComplex, models.CASCADE)
Hervé  MENAGER's avatar
Hervé MENAGER committed
249
250
    cc_nb = models.IntegerField(
        'Number of copies of the complex in the PPI', default=1)
Hervé  MENAGER's avatar
Hervé MENAGER committed
251
252
253
254

    class Meta:
        verbose_name_plural = "Ppi complexes"

255
256
257
    def __str__(self):
        return 'PPI {}, Complex {} ({})'.format(self.ppi, self.complex, self.cc_nb)

258
class Compound(models.Model):
Hervé  MENAGER's avatar
Hervé MENAGER committed
259
260
261
262
263
264
265
    canonical_smile = models.CharField(
        'Canonical Smile', unique=True, max_length=500)
    is_macrocycle = models.BooleanField('Contains one or more macrocycles')
    aromatic_ratio = models.DecimalField(
        'Aromatic ratio', max_digits=3, decimal_places=2)
    balaban_index = models.DecimalField(
        'Balaban index', max_digits=3, decimal_places=2)
266
    fsp3 = models.DecimalField('Fsp3', max_digits=3, decimal_places=2)
Hervé  MENAGER's avatar
Hervé MENAGER committed
267
268
269
270
271
272
273
274
275
276
    gc_molar_refractivity = models.DecimalField(
        'GC Molar Refractivity', max_digits=5, decimal_places=2)
    log_d = models.DecimalField(
        'LogD (Partition coefficient octanol-1/water, with pKa information)', max_digits=4, decimal_places=2)
    a_log_p = models.DecimalField(
        'ALogP (Partition coefficient octanol-1/water)', max_digits=4, decimal_places=2)
    mean_atom_vol_vdw = models.DecimalField(
        'Mean atom volume computed with VdW radii', max_digits=4, decimal_places=2)
    molecular_weight = models.DecimalField(
        'Molecular weight', max_digits=6, decimal_places=2)
277
278
279
280
    nb_acceptor_h = models.IntegerField('Number of hydrogen bond acceptors')
    nb_aliphatic_amines = models.IntegerField('Number of aliphatics amines')
    nb_aromatic_bonds = models.IntegerField('Number of aromatic bonds')
    nb_aromatic_ether = models.IntegerField('Number of aromatic ethers')
Hervé  MENAGER's avatar
Hervé MENAGER committed
281
282
283
284
    nb_aromatic_sssr = models.IntegerField(
        'Number of aromatic Smallest Set of System Rings (SSSR)')
    nb_atom = models.IntegerField('Number of atoms')
    nb_atom_non_h = models.IntegerField('Number of non hydrogen atoms')
285
286
    nb_benzene_like_rings = models.IntegerField('Number of benzene-like rings')
    nb_bonds = models.IntegerField('Number of bonds')
Hervé  MENAGER's avatar
Hervé MENAGER committed
287
288
289
290
291
292
293
294
295
296
297
298
299
300
    nb_bonds_non_h = models.IntegerField(
        'Number of bonds not involving a hydrogen')
    nb_br = models.IntegerField('Number of Bromine atoms')
    nb_c = models.IntegerField('Number of Carbon atoms')
    nb_chiral_centers = models.IntegerField('Number of chiral centers')
    nb_circuits = models.IntegerField('Number of circuits')
    nb_cl = models.IntegerField('Number of Chlorine atoms')
    nb_csp2 = models.IntegerField('Number of sp2-hybridized carbon atoms')
    nb_csp3 = models.IntegerField('Number of sp3-hybridized carbon atoms')
    nb_donor_h = models.IntegerField('Number of hydrogen bond donors')
    nb_double_bonds = models.IntegerField('Number of double bonds')
    nb_f = models.IntegerField('Number of fluorine atoms')
    nb_i = models.IntegerField('Number of iodine atoms')
    nb_multiple_bonds = models.IntegerField('Number of multiple bonds')
301
    nb_n = models.IntegerField('Number of nitrogen atoms')
Hervé  MENAGER's avatar
Hervé MENAGER committed
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
    nb_o = models.IntegerField('Number of oxygen atoms')
    nb_rings = models.IntegerField('Number of rings')
    nb_rotatable_bonds = models.IntegerField('Number of rotatable bonds')
    randic_index = models.DecimalField(
        'Randic index', max_digits=4, decimal_places=2)
    rdf070m = models.DecimalField(
        'RDF070m, radial distribution function weighted by the atomic masses at 7Å', max_digits=5, decimal_places=2)
    rotatable_bond_fraction = models.DecimalField(
        'Fraction of rotatable bonds', max_digits=3, decimal_places=2)
    sum_atom_polar = models.DecimalField(
        'Sum of atomic polarizabilities', max_digits=5, decimal_places=2)
    sum_atom_vol_vdw = models.DecimalField(
        'Sum of atom volumes computed with VdW radii', max_digits=6, decimal_places=2)
    tpsa = models.DecimalField(
        'Topological Polar Surface Area (TPSA)', max_digits=5, decimal_places=2)
    ui = models.DecimalField(
        'Unsaturation index', max_digits=4, decimal_places=2)
    wiener_index = models.IntegerField('Wiener index')
    common_name = models.CharField(
        'Common name', unique=True, max_length=20, blank=True, null=True)
    pubchem_id = models.CharField(
        'Pubchem ID', max_length=10, blank=True, null=True)
    chemspider_id = models.CharField(
        'Chemspider ID', unique=True, max_length=10, blank=True, null=True)
    chembl_id = models.CharField(
        'Chembl ID', max_length=30, blank=True, null=True)
    iupac_name = models.CharField(
        'IUPAC name', max_length=255, blank=True, null=True)
    mddr_compound = models.ForeignKey(
331
        'MDDRCompoundImport', models.CASCADE, blank=True, null=True)
332

333
334
    objects = DataFrameManager()

Hervé  MENAGER's avatar
Hervé MENAGER committed
335
336
337
338
339
340
    @property
    def biblio_refs(self):
        """
        return all RefCompoundBiblio related to this complex
        """
        return RefCompoundBiblio.objects.filter(compound=self)
341

342
343
344
345
346
347
348
349
350
351
352
353
354
    @property
    def pfam_ids(self):
        """
        return all PFAM ids for the domain of the proteins of the bound
        complexes in the PPIs this compound has an action on
        """
        pfam_ids = set()
        for ca in self.compoundaction_set.all():
            ca.get_complexes()
            for bound_complex in ca.ppi.get_ppi_bound_complexes():
                pfam_ids.add(bound_complex.complex.domain.pfam_id)
        return pfam_ids

355
356
357
358
359
360
361
362
363
364
    @property
    def compound_action_pdb_ids(self):
        """
        return all PDB codes of the corresponding compound actions
        """
        pdb_ids = set()
        for ca in self.compoundaction_set.all():
            pdb_ids.add(ca.pdb_id)
        return pdb_ids

365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
414
415
416
417
    @property
    def hba_hbd(self):
        return self.nb_acceptor_h + self.nb_donor_h

    @property
    def lipinsky_mw(self):
        return self.molecular_weight <= 500

    @property
    def lipinsky_hba(self):
        return self.nb_acceptor_h <= 10

    @property
    def lipinsky_hbd(self):
        return self.nb_donor_h <= 5

    @property
    def lipinsky_a_log_p(self):
        return self.a_log_p <= 5

    @property
    def lipinsky_global(self):
        return int(self.lipinsky_mw) + int(self.lipinsky_hba) + \
            int(self.lipinsky_hbd) + int(self.lipinsky_a_log_p) >= 3

    @property
    def veber_hba_hbd(self):
        return self.nb_acceptor_h + self.nb_donor_h <= 12

    @property
    def veber_tpsa(self):
        return self.tpsa <= 140

    @property
    def veber_rb(self):
        return self.nb_rotatable_bonds <= 10

    @property
    def veber_global(self):
        return self.veber_rb and (self.veber_hba_hbd or self.veber_tpsa)

    @property
    def pfizer_a_log_p(self):
        return self.a_log_p <= 3

    @property
    def pfizer_tpsa(self):
        return self.tpsa >= 75

    @property
    def pfizer_global(self):
        return self.pfizer_a_log_p and self.pfizer_tpsa

418
419
    @property
    def best_pXC50_activity(self):
420
        return self.compoundactivityresult_set.aggregate(Max('activity'))['activity__max']
421
422
423
424
425
426

    @property
    def best_pXC50_compound_activity_result(self):
        best_pXC50_activity = self.best_pXC50_activity
        if best_pXC50_activity is None:
            return None
427
        return self.compoundactivityresult_set.filter(activity=best_pXC50_activity)[0]
428

429
430
431
432
433
    @property
    def le(self):
        """
        LE: Ligand Efficiency
        """
434
435
436
437
        best_pXC50_activity = self.best_pXC50_activity
        if best_pXC50_activity is None:
            return None
        return (1.37 * float(best_pXC50_activity))/self.nb_atom_non_h
438
439
440
441
442
443

    @property
    def lle(self):
        """
        LLE: Lipophilic Efficiency
        """
444
445
446
447
        best_pXC50_activity = self.best_pXC50_activity
        if best_pXC50_activity is None:
            return None
        return float(best_pXC50_activity - self.a_log_p)     
448

449
    @property
450
    def best_pXC50_activity_ppi_name(self):
451
        """
452
        Name of the PPI corresponding to the best PXC50 activity
453
        """
454
455
456
        best_activity_car = self.best_pXC50_compound_activity_result
        if best_activity_car is None:
            return None
457
458
459
        ppi_name = best_activity_car.test_activity_description.ppi.name
        return ppi_name

460
461
462
463
464
465
466
467
468
469
470
471
472
473
474
    @property
    def bioch_tests_count(self):
        """
        return the number of associated biochemical tests
        """
        return self.compoundactivityresult_set.all().filter(test_activity_description__test_type='BIOCH').count()

    @property
    def cell_tests_count(self):
        """
        return the number of associated cell tests
        """
        return self.compoundactivityresult_set.all().filter(test_activity_description__test_type='CELL').count()


475
476
477
class LeLleBiplotData(models.Model):
    le_lle_biplot_data = models.CharField('LE-LLE biplot JSON data', max_length=150000, blank=True, null=True)

478
class MDDRActivityClass(models.Model):
Hervé  MENAGER's avatar
Hervé MENAGER committed
479
    name = models.CharField('Activity Class', max_length=100, unique=True)
480
481
482
483
484

    class Meta:
        verbose_name_plural = "MDDR activity classes"

    def __str__(self):
485
        return self.name
486

Hervé  MENAGER's avatar
Hervé MENAGER committed
487

488
class MDDRCompoundImport(models.Model):
489
490

    MDDR_DEVELOPMENT_PHASES = (
Hervé  MENAGER's avatar
Hervé MENAGER committed
491
492
493
494
495
496
497
498
499
500
501
502
503
504
505
506
        ('Biological Testing', ''),
        ('Preclinical', ''),
        ('Phase III', ''),
        ('Phase II', ''),
        ('Phase I/II', ''),
        ('Phase I', ''),
        ('Launched', ''),
        ('Pre-Registered', ''),
        ('Not Applicable', ''),
        ('Discontinued', ''),
        ('Clinical', ''),
        ('Withdrawn', ''),
        ('Registered', ''),
        ('Not Determined', ''),
        ('Phase II/III', ''),
        ('IND Filed', ''),
507
508
    )

Hervé  MENAGER's avatar
Hervé MENAGER committed
509
510
511
512
513
514
515
    mddr_name = models.CharField('MDDR name', max_length=40)
    dvpmt_phase = models.CharField(
        'Development phase', max_length=20, choices=MDDR_DEVELOPMENT_PHASES)
    canonical_smile = models.CharField(
        'Canonical Smile', max_length=500, blank=True, null=True)
    # TODO index this table on canonical_smile
    db_import_date = models.DateTimeField('MDDR release year/month')
516
    activity_classes = models.ManyToManyField(MDDRActivityClass)
Hervé  MENAGER's avatar
Hervé MENAGER committed
517

518
519
    class Meta:
        # over multiple releases of the MDDR database, the same compound can evolve in its development phase
Hervé  MENAGER's avatar
Hervé MENAGER committed
520
521
        # the same compound can have different names and development phases in
        # the same MDDR release
522
        unique_together = (('mddr_name', 'dvpmt_phase', 'canonical_smile'),)
Hervé  MENAGER's avatar
Hervé MENAGER committed
523
        verbose_name_plural = "MDDR compound imports"
Hervé  MENAGER's avatar
Hervé MENAGER committed
524

525
526
527
    def __str__(self):
        return "{}, {}".format(self.mddr_name, self.dvpmt_phase)

Hervé  MENAGER's avatar
Hervé MENAGER committed
528

529
class MDDRSimilarity(models.Model):
Hervé  MENAGER's avatar
Hervé MENAGER committed
530
531
532
533
534
    canonical_smile_ippidb = models.CharField(
        'Canonical Smile for IPPIDB compound', max_length=500, unique=True, blank=True, null=True)
    canonical_smile_mddr = models.CharField(
        'Canonical Smile for MDDR Compound', max_length=500, unique=True, blank=True, null=True)
    tanimoto = models.DecimalField('Tanimoto', max_digits=6, decimal_places=5)
Hervé  MENAGER's avatar
Hervé MENAGER committed
535
536

    class Meta:
537
        unique_together = (('canonical_smile_ippidb', 'canonical_smile_mddr'),)
Hervé  MENAGER's avatar
Hervé MENAGER committed
538
        verbose_name_plural = "MDDR similarities"
539

Hervé  MENAGER's avatar
Hervé MENAGER committed
540

541
542
class CellLine(models.Model):
    name = models.CharField('Name', max_length=50, unique=True)
Hervé  MENAGER's avatar
Hervé MENAGER committed
543

544
545
546
    def __str__(self):
        return self.name

Hervé  MENAGER's avatar
Hervé MENAGER committed
547

548
549
550
551
552
553
554
555
556
557
class TestActivityDescription(models.Model):
    TEST_TYPES = (
        ('BIOCH', 'Biochemical assay'),
        ('CELL', 'Cellular assay')
    )
    TEST_MODULATION_TYPES = (
        ('B', 'Binding'),
        ('I', 'Inhibition'),
        ('S', 'Stabilization')
    )
558
559
560
561
    PROTEIN_BOUND_CONSTRUCTS = (
        ('F', 'Full length'),
        ('U', 'Unspecified')
    )
562
    biblio = models.ForeignKey(Bibliography, models.CASCADE)
563
    protein_domain_bound_complex = models.ForeignKey(ProteinDomainBoundComplex, models.CASCADE)
564
    ppi = models.ForeignKey(Ppi, models.CASCADE, blank=True, null=True)
Hervé  MENAGER's avatar
Hervé MENAGER committed
565
    test_name = models.CharField('Test name', max_length=100)
566
567
    is_primary = models.BooleanField('Is primary')
    protein_bound_construct = models.CharField('Protein bound construct', max_length=5, choices=PROTEIN_BOUND_CONSTRUCTS, blank=True, null=True)
568
    test_type = models.CharField('Test type', max_length=5, choices=TEST_TYPES)
Hervé  MENAGER's avatar
Hervé MENAGER committed
569
570
571
572
    test_modulation_type = models.CharField(
        'Test modulation type', max_length=1, choices=TEST_MODULATION_TYPES)
    nb_active_compounds = models.IntegerField(
        'Total number of active compounds')
573
    cell_line = models.ForeignKey(CellLine, models.CASCADE, blank=True, null=True)
574

Hervé  MENAGER's avatar
Hervé MENAGER committed
575
    def get_complexes(self):
576
577
578
579
        """
        get the complexes tested for this PPI
        depends on the modulation type
        """
Hervé  MENAGER's avatar
Hervé MENAGER committed
580
        if self.test_modulation_type == 'I':
581
582
583
            return self.ppi.get_ppi_complexes()
        else:
            return self.ppi.get_ppi_bound_complexes()
584

585
586
587
588
589
590
591
    @property
    def protein_domain_partner_complex(self):
        for ppic in self.ppi.ppicomplex_set.all():
            if hasattr(ppic.complex,'proteindomainpartnercomplex'):
                return ppic.complex.proteindomainpartnercomplex
        return None

Hervé  MENAGER's avatar
Hervé MENAGER committed
592

593
class CompoundActivityResult(models.Model):
594
595
596
597
598
    MODULATION_TYPES = (
        ('B', 'Binding'),
        ('I', 'Inhibition'),
        ('S', 'Stabilization')
    )
Hervé  MENAGER's avatar
Hervé MENAGER committed
599
    ACTIVITY_TYPES = (
Hervé  MENAGER's avatar
Hervé MENAGER committed
600
601
602
603
        ('pIC50', 'pIC50 (half maximal inhibitory concentration, -log10)'),
        ('pEC50', 'pEC50 (half maximal effective concentration, -log10)'),
        ('pKd', 'pKd (dissociation constant, -log10)'),
        ('pKi', 'pKi (inhibition constant, -log10)'),
Hervé  MENAGER's avatar
Hervé MENAGER committed
604
    )
605
606
    compound = models.ForeignKey(Compound, models.CASCADE)
    test_activity_description = models.ForeignKey(TestActivityDescription, models.CASCADE)
Hervé  MENAGER's avatar
Hervé MENAGER committed
607
608
609
610
    activity_type = models.CharField(
        'Activity type', max_length=5, choices=ACTIVITY_TYPES)
    activity = models.DecimalField(
        'Activity', max_digits=12, decimal_places=10)
611
612
    inhibition_percentage = models.DecimalField(
        'Inhibition percentage', max_digits=3, decimal_places=0, null=True)
Hervé  MENAGER's avatar
Hervé MENAGER committed
613
614
    modulation_type = models.CharField(
        'Modulation type', max_length=1, choices=MODULATION_TYPES)
Hervé  MENAGER's avatar
Hervé MENAGER committed
615
616

    class Meta:
Hervé  MENAGER's avatar
Hervé MENAGER committed
617
618
619
        unique_together = (
            ('compound', 'test_activity_description', 'activity_type'),)

620
621
    def __str__(self):
        return 'Compound activity result for {} test {} on {}'.format(self.activity_type, self.test_activity_description.id, self.compound.id)
Hervé  MENAGER's avatar
Hervé MENAGER committed
622

623
624
625
    def is_best(self):
        return self.compound.best_pXC50_compound_activity_result.id == self.id

626
class TestCytotoxDescription(models.Model):
627
    biblio = models.ForeignKey(Bibliography, models.CASCADE)
Hervé  MENAGER's avatar
Hervé MENAGER committed
628
    test_name = models.CharField('Cytotoxicity test name', max_length=100)
629
    cell_line = models.ForeignKey(CellLine, models.CASCADE)
Hervé  MENAGER's avatar
Hervé MENAGER committed
630
631
632
    compound_concentration = models.DecimalField(
        'Compound concentration in μM', max_digits=7, decimal_places=3, blank=True, null=True)

Hervé  MENAGER's avatar
Hervé MENAGER committed
633

634
class CompoundCytotoxicityResult(models.Model):
635
636
    compound = models.ForeignKey(Compound, models.CASCADE)
    test_cytotoxicity_description = models.ForeignKey(TestCytotoxDescription, models.CASCADE)
637
    toxicity = models.BooleanField('Toxicity', default=False)
Hervé  MENAGER's avatar
Hervé MENAGER committed
638
639

    class Meta:
640
        unique_together = (('compound', 'test_cytotoxicity_description'),)
641

642
643
644
    def __str__(self):
        return 'Compound cytotoxicity result for test {} on {}'.format(self.test_cytotoxicity_description.id, self.compound.id)

Hervé  MENAGER's avatar
Hervé MENAGER committed
645

646
class TestPKDescription(models.Model):
647
648
649
650
651
652
    ADMINISTRATION_MODES = (
        ('IV', ''),
        ('PO', ''),
        ('IP', ''),
        ('SL', 'SL')
    )
653
    biblio = models.ForeignKey(Bibliography, models.CASCADE)
Hervé  MENAGER's avatar
Hervé MENAGER committed
654
    test_name = models.CharField('Pharmacokinetic test name', max_length=100)
655
    organism = models.ForeignKey(Taxonomy, models.CASCADE)
Hervé  MENAGER's avatar
Hervé MENAGER committed
656
657
    administration_mode = models.CharField(
        'Administration mode', max_length=2, choices=ADMINISTRATION_MODES, blank=True, null=True)
658
659
    concentration = models.DecimalField(
        'Concentration in mg/l', max_digits=7, decimal_places=3, blank=True, null=True)
Hervé  MENAGER's avatar
Hervé MENAGER committed
660
    dose = models.DecimalField(
661
        'Dose in mg/kg', max_digits=9, decimal_places=4, blank=True, null=True)
Hervé  MENAGER's avatar
Hervé MENAGER committed
662
663
664
    dose_interval = models.IntegerField(
        'Dose interval, in hours', blank=True, null=True)

665
666

class CompoundPKResult(models.Model):
667
668
    compound = models.ForeignKey(Compound, models.CASCADE)
    test_pk_description = models.ForeignKey(TestPKDescription, models.CASCADE)
669
    tolerated = models.NullBooleanField('Tolerated', null=True)
Hervé  MENAGER's avatar
Hervé MENAGER committed
670
671
672
673
674
675
676
677
678
679
680
681
    auc = models.IntegerField(
        'Area under curve (ng.mL-1.hr)', blank=True, null=True)
    clearance = models.DecimalField(
        'Clearance (mL/hr)', max_digits=7, decimal_places=3, blank=True, null=True)
    cmax = models.DecimalField(
        'Maximal concentration (ng/mL)', max_digits=7, decimal_places=3, blank=True, null=True)
    oral_bioavailability = models.IntegerField(
        'Oral Bioavailability (%F)', blank=True, null=True)
    t_demi = models.IntegerField('t½', blank=True, null=True)
    t_max = models.IntegerField('tmax', blank=True, null=True)
    voldistribution = models.DecimalField(
        'Volume distribution (Vd)', max_digits=5, decimal_places=2, blank=True, null=True)
Hervé  MENAGER's avatar
Hervé MENAGER committed
682
683

    class Meta:
684
        unique_together = (('compound', 'test_pk_description'),)
Hervé  MENAGER's avatar
Hervé MENAGER committed
685

686
687
688
    def __str__(self):
        return 'Compound PK result for test {} on {}'.format(self.test_pk_description.id, self.compound.id)

Hervé  MENAGER's avatar
Hervé MENAGER committed
689

690
class CompoundAction(models.Model):
691
692
    ACTIVATION_MODES = (
        ('O', 'Orthosteric'),
693
694
        ('A', 'Allosteric'),
        ('U', 'Unspecified')
695
    )
696
    compound = models.ForeignKey(Compound, models.CASCADE)
Hervé  MENAGER's avatar
Hervé MENAGER committed
697
698
    activation_mode = models.CharField(
        'Activation mode', max_length=1, choices=ACTIVATION_MODES)
699
    ppi = models.ForeignKey(Ppi, models.CASCADE)
700
    pdb_id = models.CharField('PDB ID', max_length=4, blank=True, null=True)
Hervé  MENAGER's avatar
Hervé MENAGER committed
701
702
    nb_copy_compounds = models.IntegerField(
        'Number of copies for the compound')
Hervé  MENAGER's avatar
Hervé MENAGER committed
703
704

    class Meta:
Hervé  MENAGER's avatar
Hervé MENAGER committed
705
706
707
        unique_together = (('ppi', 'compound', 'activation_mode', 'pdb_id'),)

    def get_complexes(self):
708
709
710
711
        """
        get the complexes involved in the compound action
        which are always the bound complexes
        """
712
        return self.ppi.get_ppi_bound_complexes()
Hervé  MENAGER's avatar
Hervé MENAGER committed
713

Hervé  MENAGER's avatar
Hervé MENAGER committed
714

715
class RefCompoundBiblio(models.Model):
716
717
    compound = models.ForeignKey(Compound, models.CASCADE)
    bibliography = models.ForeignKey(Bibliography, models.CASCADE)
Hervé  MENAGER's avatar
Hervé MENAGER committed
718
719
    compound_name = models.CharField(
        'Compound name in the publication', max_length=50)
Hervé  MENAGER's avatar
Hervé MENAGER committed
720
721

    class Meta:
722
        unique_together = (('compound', 'bibliography'),)