modifications for issue #330 feature request. To use, liftover_level …

VariantValidator/modules/liftover.py

@@ -38,6 +38,9 @@ def liftover(hgvs_genomic, build_from, build_to, hn, reverse_normalizer, evm, va
     :param reverse_normalizer:
     :param evm:
     :param validator: Validator obj
+    :param specify_tx: Specify a specific transcript = False or str(transcript_ID)
+    :param liftover_level: False or 'primary'
+    :param g_to_g: True or False
     :return:
     """
 
@@ -131,7 +134,7 @@ def liftover(hgvs_genomic, build_from, build_to, hn, reverse_normalizer, evm, va
     # Get a list of overlapping RefSeq transcripts
     # Note, due to 0 base positions in UTA (I think) occasionally tx will
     rts_list = validator.hdp.get_tx_for_region(hgvs_genomic.ac, 'splign', hgvs_genomic.posedit.pos.start.base - 1,
-                                               hgvs_genomic.posedit.pos.end.base) #- 1)
+                                               hgvs_genomic.posedit.pos.end.base)  # - 1)
     rts_dict = {}
     tx_list = False
     if g_to_g is True:
@@ -160,6 +163,8 @@ def liftover(hgvs_genomic, build_from, build_to, hn, reverse_normalizer, evm, va
             for op in options:
                 sff = None
                 sft = None
+                if liftover_level is None:
+                    continue
                 if op[1].startswith('NC_'):
                     if build_to.startswith('GRC'):
                         sft = seq_data.to_chr_num_refseq(op[1], build_to)

VariantValidator/modules/mappers.py

@@ -696,15 +696,20 @@ def transcripts_to_gene(variant, validator, select_transcripts_dict_plus_version
     return False
 
 
-def final_tx_to_multiple_genomic(variant, validator, tx_variant):
+def final_tx_to_multiple_genomic(variant, validator, tx_variant, liftover_level=False):
 
     warnings = ''
     rec_var = ''
     gap_compensation = True
 
     # Multiple genomic variants
     # multi_gen_vars = []
-    variant.hgvs_coding = validator.hp.parse_hgvs_variant(str(tx_variant))
+    try:
+        tx_variant.ac
+        variant.hgvs_coding = tx_variant
+    except AttributeError:
+        variant.hgvs_coding = validator.hp.parse_hgvs_variant(str(tx_variant))
+
     # Gap gene black list
     if variant.gene_symbol:
         # If the gene symbol is not in the list, the value False will be returned
@@ -727,10 +732,17 @@ def final_tx_to_multiple_genomic(variant, validator, tx_variant):
     multi_list = []
     mapping_options = validator.hdp.get_tx_mapping_options(variant.hgvs_coding.ac)
     mapping_options = sorted(mapping_options, key=itemgetter(1))
+
     for alt_chr in mapping_options:
-        if ('NC_' in alt_chr[1] or 'NT_' in alt_chr[1] or 'NW_' in alt_chr[1]) and \
-                alt_chr[2] == validator.alt_aln_method:
-            multi_list.append(alt_chr[1])
+        if liftover_level is None:
+            multi_list.append(variant.genomic_g.split(":")[0])
+        elif liftover_level is 'primary':
+            if ('NC_' in alt_chr[1]) and alt_chr[2] == validator.alt_aln_method:
+                multi_list.append(alt_chr[1])
+        else:
+            if ('NC_' in alt_chr[1] or 'NT_' in alt_chr[1] or 'NW_' in alt_chr[1]) and \
+                    alt_chr[2] == validator.alt_aln_method:
+                multi_list.append(alt_chr[1])
 
     for alt_chr in multi_list:
         logger.debug("Trying to do final gap mapping with %s", alt_chr)

VariantValidator/modules/vvMixinCore.py

@@ -29,12 +29,18 @@ class Mixin(vvMixinConverters.Mixin):
     It's added to the Validator object in the vvObjects file.
     """
 
-    def validate(self, batch_variant, selected_assembly, select_transcripts, transcript_set="refseq"):
+    def validate(self,
+                 batch_variant,
+                 selected_assembly,
+                 select_transcripts,
+                 transcript_set="refseq",
+                 liftover_level=False):
         """
         This is the main validator function.
         :param batch_variant: A string containing the variant to be validated
         :param selected_assembly: The version of the genome assembly to use.
         :param select_transcripts: Can be an array of different transcripts, or 'all'
+        :param liftover_level: True or False - liftover to different gene/genome builds or not
         Selecting multiple transcripts will lead to a multiple variant outputs.
         :param transcript_set: 'refseq' or 'ensembl'. Currently only 'refseq' is supported
         :return:
@@ -52,14 +58,12 @@ def validate(self, batch_variant, selected_assembly, select_transcripts, transcr
                             transcript_set)
 
         primary_assembly = None
-
         self.selected_assembly = selected_assembly
         self.select_transcripts = select_transcripts
 
+        # Validation
+        ############
         try:
-            # Validation
-            ############
-
             # Create a dictionary of transcript ID : ''
             select_transcripts_dict = {}
             select_transcripts_dict_plus_version = {}
@@ -670,7 +674,10 @@ def validate(self, batch_variant, selected_assembly, select_transcripts, transcr
                     variant.gene_symbol = ''
 
                 if tx_variant != '':
-                    multi_gen_vars = mappers.final_tx_to_multiple_genomic(variant, self, tx_variant)
+                    multi_gen_vars = mappers.final_tx_to_multiple_genomic(variant,
+                                                                          self,
+                                                                          tx_variant,
+                                                                          liftover_level=liftover_level)
 
                 else:
                     # HGVS genomic in the absence of a transcript variant
@@ -1066,8 +1073,10 @@ def validate(self, batch_variant, selected_assembly, select_transcripts, transcr
                 ref_records = self.db.get_urls(variant.output_dict())
                 if ref_records != {}:
                     variant.reference_sequence_records = ref_records
-                if (variant.output_type_flag == 'intergenic') or ('grch37' not in variant.primary_assembly_loci.keys())\
-                        or ('grch38' not in variant.primary_assembly_loci.keys()):
+                if (variant.output_type_flag == 'intergenic' and liftover_level is not None) or \
+                        ('grch37' not in variant.primary_assembly_loci.keys())\
+                        or ('grch38' not in variant.primary_assembly_loci.keys()
+                            and liftover_level is not None):
 
                     # Simple cache
                     lo_cache = {}
@@ -1104,13 +1113,18 @@ def validate(self, batch_variant, selected_assembly, select_transcripts, transcr
                         g_to_g = False
                         if variant.output_type_flag != 'intergenic':
                             g_to_g = True
-                        # Liftover
+
+                        # Lift-over
                         if genomic_position_info[g_p_key]['hgvs_genomic_description'] not in lo_cache.keys():
                             lifted_response = liftover(genomic_position_info[g_p_key]['hgvs_genomic_description'],
                                                        build_from,
                                                        build_to, variant.hn, variant.reverse_normalizer,
-                                                       variant.evm, self, specify_tx=False, liftover_level=False,
+                                                       variant.evm,
+                                                       self,
+                                                       specify_tx=False,
+                                                       liftover_level=liftover_level,
                                                        g_to_g=g_to_g)
+
                             lo_cache[genomic_position_info[g_p_key]['hgvs_genomic_description']] = lifted_response
                         else:
                             lifted_response = lo_cache[genomic_position_info[g_p_key]['hgvs_genomic_description']]

tests/test_inputs.py

@@ -30501,6 +30501,29 @@ def test_issue_326(self):
         print(results)
         assert 'NM_000546.6:c.1182_*1insT' in results.keys()
 
+    def test_issue_330a(self):
+        variant = 'NM_001353.6:c.2del'
+        results = self.vv.validate(variant, 'GRCh37', 'all', liftover_level=None).format_as_dict(test=True)
+        print(results)
+        assert 'grch37' in results['NM_001353.6:c.2del']['primary_assembly_loci'].keys()
+        assert 'grch38' not in results['NM_001353.6:c.2del']['primary_assembly_loci'].keys()
+
+    def test_issue_330b(self):
+        variant = 'NM_001040114.1:c.3055_3056inv'
+        results = self.vv.validate(variant, 'GRCh37', 'all', liftover_level='primary').format_as_dict(test=True)
+        print(results)
+        assert 'grch37' in results['NM_001040114.1:c.3055_3056inv']['primary_assembly_loci'].keys()
+        assert 'grch38' in results['NM_001040114.1:c.3055_3056inv']['primary_assembly_loci'].keys()
+        assert len(results['NM_001040114.1:c.3055_3056inv']['alt_genomic_loci']) == 0
+
+    def test_issue_330c(self):
+        variant = 'NC_000017.10:g.48279242G>T'
+        results = self.vv.validate(variant, 'GRCh37', 'all', liftover_level='primary').format_as_dict(test=True)
+        print(results)
+        assert 'grch37' in results['intergenic_variant_1']['primary_assembly_loci'].keys()
+        assert 'grch38' in results['intergenic_variant_1']['primary_assembly_loci'].keys()
+        assert len(results['intergenic_variant_1']['alt_genomic_loci']) == 0
+
 
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 # Copyright (C) 2016-2022 VariantValidator Contributors