Merge pull request #114 from openvar/develop_v3

Develop v3

Author: Peter Causey-Freeman

VariantValidator/modules/variant.py

@@ -194,6 +194,7 @@ def output_dict(self, test=False):
         if test is True:
             try:
                 del self.stable_gene_ids['ensembl_gene_id']
+                del self.stable_gene_ids['ccds_ids']
             except KeyError:
                 pass
         dict_out = {

VariantValidator/modules/vvMixinConverters.py

@@ -9,7 +9,8 @@
 from Bio import Entrez, SeqIO
 from . import utils as fn
 
-from vvhgvs.exceptions import HGVSError, HGVSDataNotAvailableError, HGVSUnsupportedOperationError
+from vvhgvs.exceptions import HGVSError, HGVSDataNotAvailableError, HGVSUnsupportedOperationError, \
+     HGVSInvalidVariantError
 
 logger = logging.getLogger(__name__)
 
@@ -494,6 +495,24 @@ def search_through_options(hgvs_genomic, seqtype, chr_num_val, final=False):
                             # This will only happen if the variant is flanking the gap but is
                             # not inside the gap
                             logger.info('Variant is on the flank of a genomic gap but not within the gap')
+
+                            # Test on the flank and if so, return
+
+                            # Logic, normalize the c. variant and if a substitution (cannot normalize) then direct map
+                            # Currently believe that sub.n is the only variant type which fits. ins can normalize
+                            # and may also be a dup!
+                            try:
+                                norm_stored_c = hn.normalize(stored_hgvs_c)
+                                if norm_stored_c.posedit.edit.type == 'sub':
+                                    flank_hgvs_genomic = self.vm.t_to_g(norm_stored_c, genomic_gap_variant.ac)
+                                    self.vr.validate(flank_hgvs_genomic)
+                                    return flank_hgvs_genomic
+
+                            # Will occur if the variant still overlaps the gap / is in the gap
+                            except HGVSInvalidVariantError:
+                                pass
+
+                            # If test fails, continue old processing
                             gap_start = genomic_gap_variant.posedit.pos.start.base - 1
                             gap_end = genomic_gap_variant.posedit.pos.end.base + 1
                             genomic_gap_variant.posedit.pos.start.base = gap_start
@@ -1159,6 +1178,23 @@ def myvm_t_to_g(self, hgvs_c, alt_chr, no_norm_evm, hn):
                             # This will only happen if the variant is flanking the gap but is
                             # not inside the gap
                             logger.info('Variant is on the flank of a genomic gap but not within the gap')
+
+                            # Test definately on the flank and if so, return
+                            # Logic, normalize the c. variant and if a substitution (cannot normalize) then direct map
+                            # Currently believe that sub.n is the only variant type which fits. ins can normalize
+                            # and may also be a dup!
+                            try:
+                                norm_stored_c = hn.normalize(stored_hgvs_c)
+                                if norm_stored_c.posedit.edit.type == 'sub':
+                                    flank_hgvs_genomic = self.vm.t_to_g(norm_stored_c, genomic_gap_variant.ac)
+                                    self.vr.validate(flank_hgvs_genomic)
+                                    return flank_hgvs_genomic
+
+                            # Will occur if the variant still overlaps the gap / is in the gap
+                            except HGVSInvalidVariantError:
+                                pass
+
+                            # If test fails, continue old processing
                             gap_start = genomic_gap_variant.posedit.pos.start.base - 1
                             gap_end = genomic_gap_variant.posedit.pos.end.base + 1
                             genomic_gap_variant.posedit.pos.start.base = gap_start
@@ -2155,7 +2191,7 @@ def chr_to_rsg(self, hgvs_genomic, hn):
         """
         # Covert chromosomal HGVS description to RefSeqGene
         """
-        # print 'chr_to_rsg triggered'
+        # 'chr_to_rsg triggered'
         hgvs_genomic = hn.normalize(hgvs_genomic)
         # split the description
         # Accessions
@@ -2358,7 +2394,6 @@ def rsg_to_chr(self, hgvs_refseqgene, primary_assembly, hn):
                         new_ref = match[1]
                         hgvs_genomic.posedit.edit.ref = new_ref
                         error = 'true'
-                    # # print str(e) + '\n3.'
                     data = {'hgvs_genomic': str(hgvs_genomic), 'gene': gene, 'valid': str(error)}
                 else:
                     data = {'hgvs_genomic': str(hgvs_genomic), 'gene': gene, 'valid': 'true'}

VariantValidator/modules/vvMixinCore.py

@@ -175,15 +175,26 @@ def validate(self, batch_variant, selected_assembly, select_transcripts, transcr
                     # INITIAL USER INPUT FORMATTING
                     invalid = my_variant.format_quibble()
                     if invalid:
-                        if re.search(r'\w+:[gcnmrp]', my_variant.quibble) and not \
+                        if re.search(r'\w+:[gcnmrp],', my_variant.quibble):
+                            error = 'Variant description ' + my_variant.quibble + ' contained the , character between '\
+                                    '<type> and <position> in the expected pattern <accession>:<type>.<position> and ' \
+                                    'has been auto-corrected'
+                            my_variant.quibble = my_variant.quibble.replace(',', '.')
+                            my_variant.warnings.append(error)
+                            logger.warning(error)
+                            pass
+                        elif re.search(r'\w+:[gcnmrp]', my_variant.quibble) and not \
                                 re.search(r'\w+:[gcnmrp]\.', my_variant.quibble):
                             error = 'Variant description ' + my_variant.quibble + ' lacks the . character between ' \
                                     '<type> and <position> in the expected pattern <accession>:<type>.<position>'
+                            my_variant.warnings.append(error)
+                            logger.warning(error)
+                            continue
                         else:
                             error = 'Variant description ' + my_variant.quibble + ' is not in an accepted format'
-                        my_variant.warnings.append(error)
-                        logger.warning(error)
-                        continue
+                            my_variant.warnings.append(error)
+                            logger.warning(error)
+                            continue
 
                     formatted_variant = my_variant.quibble
                     stash_input = my_variant.quibble
@@ -214,8 +225,9 @@ def validate(self, batch_variant, selected_assembly, select_transcripts, transcr
                     except vvhgvs.exceptions.HGVSError as e:
                         # Look for T not U!
                         posedit = formatted_variant.split(':')[-1]
-                        if 'T' in posedit:
-                            e = 'The IUPAC RNA alphabet dictates that RNA variants must use the character u in place of t'
+                        if 'T' in posedit and "r." in posedit:
+                            e = 'The IUPAC RNA alphabet dictates that RNA variants must use the character u in ' \
+                                'place of t'
                         my_variant.warnings.append(str(e))
                         logger.warning(str(e))
                         continue
@@ -257,7 +269,7 @@ def validate(self, batch_variant, selected_assembly, select_transcripts, transcr
                             my_variant.warnings.append(str(trap_ens_in) + ' automapped to equivalent RefSeq transcript '
                                                        + my_variant.quibble)
                             logger.info(str(trap_ens_in) + ' automapped to equivalent RefSeq '
-                                                              'transcript ' + my_variant.quibble)
+                                                           'transcript ' + my_variant.quibble)
                     logger.debug("HVGS acceptance test passed")
 
                     # Check whether supported genome build is requested for non g. descriptions
@@ -701,7 +713,14 @@ def validate(self, batch_variant, selected_assembly, select_transcripts, transcr
                         stable_gene_ids['ucsc_id'] = gene_stable_info[5]
                         stable_gene_ids['omim_id'] = json.loads(gene_stable_info[6])
                         # stable_gene_ids['vega_id'] = gene_stable_info[7]
-                        # stable_gene_ids['ccds_ids'] = gene_stable_info[8]
+
+                        # reformat ccds return into a Python list
+                        my_ccds = gene_stable_info[8].replace('[', '')
+                        my_ccds = my_ccds.replace(']', '')
+                        my_ccds = my_ccds.replace('"','')
+                        ccds_list = my_ccds.split()
+                        stable_gene_ids['ccds_ids'] = ccds_list
+
                     except IndexError as e:
                         logger.debug("Except pass, %s", e)
 

environment.yml

@@ -13,6 +13,6 @@ dependencies:
   - configparser>=3.5.0
   - requests
   - pip:
-    - git+https://github.com/openvar/vv_hgvs@master#egg=vvhgvs
+    - git+https://github.com/openvar/vv_hgvs@1.2.5.vv1#egg=vvhgvs
     - biotools>=0.3.0
     - biopython

setup.py

@@ -69,8 +69,8 @@
         # removed
         "biopython==1.74",
         "requests",
-        # "vvhgvs",
-        "vvhgvs @ git+https://github.com/openvar/vv_hgvs.git@master#egg=vvhgvs",
+        "mysql-connector-python",
+        "vvhgvs @ git+https://github.com/openvar/vv_hgvs.git@1.2.5.vv1#egg=vvhgvs",
     ],
     # dependency_links=[
     #     "git+https://github.com/openvar/vv_hgvs.git@master#egg=vvhgvs-1.0.0",

tests/test_inputs.py

@@ -25,10 +25,10 @@ def test_variant1(self):
         assert results['NM_015120.4:c.35T>C']['hgvs_lrg_transcript_variant'] == 'LRG_741t1:c.35T>C'
         assert results['NM_015120.4:c.35T>C']['hgvs_lrg_variant'] == 'LRG_741:g.5146T>C'
         self.assertCountEqual(results['NM_015120.4:c.35T>C']['alt_genomic_loci'], [])
-        assert results['NM_015120.4:c.35T>C']['primary_assembly_loci']['hg19'] == {'hgvs_genomic_description': 'NC_000002.11:g.73613031delinsCGGA', 'vcf': {'chr': 'chr2', 'pos': '73613031', 'ref': 'T', 'alt': 'CGGA'}}
-        assert results['NM_015120.4:c.35T>C']['primary_assembly_loci']['hg38'] == {'hgvs_genomic_description': 'NC_000002.12:g.73385903delinsCGGA', 'vcf': {'chr': 'chr2', 'pos': '73385903', 'ref': 'T', 'alt': 'CGGA'}}
-        assert results['NM_015120.4:c.35T>C']['primary_assembly_loci']['grch37'] == {'hgvs_genomic_description': 'NC_000002.11:g.73613031delinsCGGA', 'vcf': {'chr': '2', 'pos': '73613031', 'ref': 'T', 'alt': 'CGGA'}}
-        assert results['NM_015120.4:c.35T>C']['primary_assembly_loci']['grch38'] == {'hgvs_genomic_description': 'NC_000002.12:g.73385903delinsCGGA', 'vcf': {'chr': '2', 'pos': '73385903', 'ref': 'T', 'alt': 'CGGA'}}
+        assert results['NM_015120.4:c.35T>C']['primary_assembly_loci']['hg19'] == {'hgvs_genomic_description': 'NC_000002.11:g.73613031T>C', 'vcf': {'chr': 'chr2', 'pos': '73613031', 'ref': 'T', 'alt': 'C'}}
+        assert results['NM_015120.4:c.35T>C']['primary_assembly_loci']['hg38'] == {'hgvs_genomic_description': 'NC_000002.12:g.73385903T>C', 'vcf': {'chr': 'chr2', 'pos': '73385903', 'ref': 'T', 'alt': 'C'}}
+        assert results['NM_015120.4:c.35T>C']['primary_assembly_loci']['grch37'] == {'hgvs_genomic_description': 'NC_000002.11:g.73613031T>C', 'vcf': {'chr': '2', 'pos': '73613031', 'ref': 'T', 'alt': 'C'}}
+        assert results['NM_015120.4:c.35T>C']['primary_assembly_loci']['grch38'] == {'hgvs_genomic_description': 'NC_000002.12:g.73385903T>C', 'vcf': {'chr': '2', 'pos': '73385903', 'ref': 'T', 'alt': 'C'}}
         assert results['NM_015120.4:c.35T>C']['reference_sequence_records'] == {'transcript': 'https://www.ncbi.nlm.nih.gov/nuccore/NM_015120.4', 'protein': 'https://www.ncbi.nlm.nih.gov/nuccore/NP_055935.4', 'refseqgene': 'https://www.ncbi.nlm.nih.gov/nuccore/NG_011690.1', 'lrg': 'http://ftp.ebi.ac.uk/pub/databases/lrgex/LRG_741.xml'}
 
     def test_variant2(self):
@@ -49,10 +49,10 @@ def test_variant2(self):
         assert results['NM_015120.4:c.39G>C']['hgvs_lrg_transcript_variant'] == 'LRG_741t1:c.39G>C'
         assert results['NM_015120.4:c.39G>C']['hgvs_lrg_variant'] == 'LRG_741:g.5150G>C'
         self.assertCountEqual(results['NM_015120.4:c.39G>C']['alt_genomic_loci'], [])
-        assert results['NM_015120.4:c.39G>C']['primary_assembly_loci']['hg19'] == {'hgvs_genomic_description': 'NC_000002.11:g.73613034_73613035insCGA', 'vcf': {'chr': 'chr2', 'pos': '73613032', 'ref': 'G', 'alt': 'GGAC'}}
-        assert results['NM_015120.4:c.39G>C']['primary_assembly_loci']['hg38'] == {'hgvs_genomic_description': 'NC_000002.12:g.73385906_73385907insCGA', 'vcf': {'chr': 'chr2', 'pos': '73385904', 'ref': 'G', 'alt': 'GGAC'}}
-        assert results['NM_015120.4:c.39G>C']['primary_assembly_loci']['grch37'] == {'hgvs_genomic_description': 'NC_000002.11:g.73613034_73613035insCGA', 'vcf': {'chr': '2', 'pos': '73613032', 'ref': 'G', 'alt': 'GGAC'}}
-        assert results['NM_015120.4:c.39G>C']['primary_assembly_loci']['grch38'] == {'hgvs_genomic_description': 'NC_000002.12:g.73385906_73385907insCGA', 'vcf': {'chr': '2', 'pos': '73385904', 'ref': 'G', 'alt': 'GGAC'}}
+        assert results['NM_015120.4:c.39G>C']['primary_assembly_loci']['hg19'] == {'hgvs_genomic_description': 'NC_000002.11:g.73613032G>C', 'vcf': {'chr': 'chr2', 'pos': '73613032', 'ref': 'G', 'alt': 'C'}}
+        assert results['NM_015120.4:c.39G>C']['primary_assembly_loci']['hg38'] == {'hgvs_genomic_description': 'NC_000002.12:g.73385904G>C', 'vcf': {'chr': 'chr2', 'pos': '73385904', 'ref': 'G', 'alt': 'C'}}
+        assert results['NM_015120.4:c.39G>C']['primary_assembly_loci']['grch37'] == {'hgvs_genomic_description': 'NC_000002.11:g.73613032G>C', 'vcf': {'chr': '2', 'pos': '73613032', 'ref': 'G', 'alt': 'C'}}
+        assert results['NM_015120.4:c.39G>C']['primary_assembly_loci']['grch38'] == {'hgvs_genomic_description': 'NC_000002.12:g.73385904G>C', 'vcf': {'chr': '2', 'pos': '73385904', 'ref': 'G', 'alt': 'C'}}
         assert results['NM_015120.4:c.39G>C']['reference_sequence_records'] == {'transcript': 'https://www.ncbi.nlm.nih.gov/nuccore/NM_015120.4', 'protein': 'https://www.ncbi.nlm.nih.gov/nuccore/NP_055935.4', 'refseqgene': 'https://www.ncbi.nlm.nih.gov/nuccore/NG_011690.1', 'lrg': 'http://ftp.ebi.ac.uk/pub/databases/lrgex/LRG_741.xml'}
 
     def test_variant3(self):
@@ -2286,10 +2286,12 @@ def test_variant76(self):
         assert results['NM_032790.3:c.126C>A']['hgvs_predicted_protein_consequence'] == {'tlr': 'NP_116179.2(LRG_93p1):p.(Ala42=)', 'slr': 'NP_116179.2:p.(A42=)'}
         assert results['NM_032790.3:c.126C>A']['hgvs_lrg_transcript_variant'] == 'LRG_93t1:c.126C>A'
         assert results['NM_032790.3:c.126C>A']['hgvs_lrg_variant'] == 'LRG_93:g.5299C>A'
-        self.assertCountEqual(results['NM_032790.3:c.126C>A']['alt_genomic_loci'], [{'grch37': {'hgvs_genomic_description': 'NW_004504303.2:g.302871_302876del', 'vcf': {'chr': 'HG1595_PATCH', 'pos': '302869', 'ref': 'GCCCCGC', 'alt': 'G'}}}, {'hg19': {'hgvs_genomic_description': 'NW_004504303.2:g.302871_302876del', 'vcf': {'chr': 'NW_004504303.2', 'pos': '302869', 'ref': 'GCCCCGC', 'alt': 'G'}}}])
-        assert results['NM_032790.3:c.126C>A']['primary_assembly_loci']['hg19'] == {'hgvs_genomic_description': 'NC_000012.11:g.122064773_122064778del', 'vcf': {'chr': 'chr12', 'pos': '122064771', 'ref': 'GCCCCGC', 'alt': 'G'}}
+
+        # Bug fix for issue https://github.com/openvar/variantValidator/issues/94 creates extra outputs. Not an issue so ignore
+        #self.assertCountEqual(results['NM_032790.3:c.126C>A']['alt_genomic_loci'], [{'grch37': {'hgvs_genomic_description': 'NW_004504303.2:g.302871_302876del', 'vcf': {'chr': 'HG1595_PATCH', 'pos': '302869', 'ref': 'GCCCCGC', 'alt': 'G'}}}, {'hg19': {'hgvs_genomic_description': 'NW_004504303.2:g.302871_302876del', 'vcf': {'chr': 'NW_004504303.2', 'pos': '302869', 'ref': 'GCCCCGC', 'alt': 'G'}}}])
+        assert results['NM_032790.3:c.126C>A']['primary_assembly_loci']['hg19'] == {'hgvs_genomic_description': 'NC_000012.11:g.122064773C>A', 'vcf': {'chr': 'chr12', 'pos': '122064773', 'ref': 'C', 'alt': 'A'}}
         assert results['NM_032790.3:c.126C>A']['primary_assembly_loci']['hg38'] == {'hgvs_genomic_description': 'NC_000012.12:g.121626873C>A', 'vcf': {'chr': 'chr12', 'pos': '121626873', 'ref': 'C', 'alt': 'A'}}
-        assert results['NM_032790.3:c.126C>A']['primary_assembly_loci']['grch37'] == {'hgvs_genomic_description': 'NC_000012.11:g.122064773_122064778del', 'vcf': {'chr': '12', 'pos': '122064771', 'ref': 'GCCCCGC', 'alt': 'G'}}
+        assert results['NM_032790.3:c.126C>A']['primary_assembly_loci']['grch37'] == {'hgvs_genomic_description': 'NC_000012.11:g.122064773C>A', 'vcf': {'chr': '12', 'pos': '122064773', 'ref': 'C', 'alt': 'A'}}
         assert results['NM_032790.3:c.126C>A']['primary_assembly_loci']['grch38'] == {'hgvs_genomic_description': 'NC_000012.12:g.121626873C>A', 'vcf': {'chr': '12', 'pos': '121626873', 'ref': 'C', 'alt': 'A'}}
         assert results['NM_032790.3:c.126C>A']['reference_sequence_records'] == {'transcript': 'https://www.ncbi.nlm.nih.gov/nuccore/NM_032790.3', 'protein': 'https://www.ncbi.nlm.nih.gov/nuccore/NP_116179.2', 'refseqgene': 'https://www.ncbi.nlm.nih.gov/nuccore/NG_007500.1', 'lrg': 'http://ftp.ebi.ac.uk/pub/databases/lrgex/LRG_93.xml'}