Merge pull request #114 from griffithlab/intron_variants

Handle variants with multiple stops in the amino acid change

.travis.yml

@@ -10,7 +10,9 @@ before_install:
   - sudo apt-get install -y ghostscript
 install:
   #Remove the following line when pvacseq-client is first pushed to the live pypi site
-  - pip install -i https://testpypi.python.org/pypi pvacseq-client
+  #This has been updated to pull from the live pypi site, instead of test pypi.
+  #Not sure if it can or needs to be deleted altogether.
+  - pip install pvacseq-client
   - pip install -e .[API]
 before_script:
   - "export DISPLAY=:99.0"

lib/fasta_generator.py

@@ -104,10 +104,15 @@ def execute(self):
                     position = int(line['protein_position'].split('-', 1)[0]) - 1
             elif variant_type == 'missense' or variant_type == 'inframe_ins':
                 wildtype_amino_acid, mutant_amino_acid = line['amino_acid_change'].split('/')
-                if wildtype_amino_acid.endswith('*'):
-                    wildtype_amino_acid = wildtype_amino_acid.replace('*', '')
-                if mutant_amino_acid.endswith('*'):
-                    mutant_amino_acid = mutant_amino_acid.replace('*', '')
+                if '*' in wildtype_amino_acid:
+                    wildtype_amino_acid = wildtype_amino_acid.split('*')[0]
+                elif 'X' in wildtype_amino_acid:
+                    wildtype_amino_acid = wildtype_amino_acid.split('X')[0]
+                if '*' in mutant_amino_acid:
+                    mutant_amino_acid = mutant_amino_acid.split('*')[0]
+                    stop_codon_added = True
+                elif 'X' in mutant_amino_acid:
+                    mutant_amino_acid = mutant_amino_acid.split('X')[0]
                     stop_codon_added = True
                 else:
                     stop_codon_added = False
@@ -124,10 +129,15 @@ def execute(self):
             elif variant_type == 'inframe_del':
                 variant_type = 'inframe_del'
                 wildtype_amino_acid, mutant_amino_acid = line['amino_acid_change'].split('/')
-                if wildtype_amino_acid.endswith('*'):
-                    wildtype_amino_acid = wildtype_amino_acid.replace('*', '')
-                if mutant_amino_acid.endswith('*'):
-                    mutant_amino_acid = mutant_amino_acid.replace('*', '')
+                if '*' in wildtype_amino_acid:
+                    wildtype_amino_acid = wildtype_amino_acid.split('*')[0]
+                elif 'X' in wildtype_amino_acid:
+                    wildtype_amino_acid = wildtype_amino_acid.split('X')[0]
+                if '*' in mutant_amino_acid:
+                    mutant_amino_acid = mutant_amino_acid.split('*')[0]
+                    stop_codon_added = True
+                elif 'X' in mutant_amino_acid:
+                    mutant_amino_acid = mutant_amino_acid.split('X')[0]
                     stop_codon_added = True
                 else:
                     stop_codon_added = False
@@ -151,7 +161,11 @@ def execute(self):
                 mutation_start_position, wildtype_subsequence = self.get_wildtype_subsequence(position, full_wildtype_sequence, wildtype_amino_acid_length, peptide_sequence_length, line)
                 mutation_end_position = mutation_start_position + wildtype_amino_acid_length
                 if wildtype_amino_acid != '-' and wildtype_amino_acid != wildtype_subsequence[mutation_start_position:mutation_end_position]:
-                    sys.exit("ERROR: There was a mismatch between the actual wildtype amino acid and the expected amino acid. Did you use the same reference build version for VEP that you used for creating the VCF?\n%s" % line)
+                    if line['amino_acid_change'].split('/')[0].count('*') > 1:
+                        print("Warning: Amino acid change is not sane - contains multiple stops. Skipping entry {}".format(line['index']))
+                        continue
+                    else:
+                        sys.exit("ERROR: There was a mismatch between the actual wildtype amino acid sequence ({}) and the expected amino acid sequence ({}). Did you use the same reference build version for VEP that you used for creating the VCF?\n{}".format(wildtype_subsequence[mutation_start_position:mutation_end_position], wildtype_amino_acid, line))
                 if stop_codon_added:
                     mutant_subsequence = wildtype_subsequence[:mutation_start_position] + mutant_amino_acid
                 else:

tests/test_data/fasta_generator/protein_change_with_X_in_wildtype_and_mutant/input.tsv

@@ -0,0 +1,2 @@
+chromosome_name	start	stop	reference	variant	gene_name	transcript_name	amino_acid_change	ensembl_gene_id	wildtype_amino_acid_sequence	downstream_amino_acid_sequence	fusion_amino_acid_sequence	variant_type	protein_position	transcript_expression	gene_expression	normal_depth	normal_vaf	tdna_depth	tdna_vaf	trna_depth	trna_vaf	index	protein_length_change
+12	96617457	96617460	CAGA	C	ELK3	ENST00000547249	AX/X	ENSG00000111145	MESAITLWQFLLQLLLDQKHEHLICWTSNDGEFKLLKA			inframe_del	38-39	NA	NA	NA	NA	NA	NA	NA	NA	39805.ELK3.ENST00000547249.inframe_del.38-39AX/X	

tests/test_data/fasta_generator/protein_change_with_multiple_asterisks/input.tsv

@@ -0,0 +1,2 @@
+chromosome_name	start	stop	reference	variant	gene_name	transcript_name	amino_acid_change	ensembl_gene_id	wildtype_amino_acid_sequence	downstream_amino_acid_sequence	fusion_amino_acid_sequence	variant_type	protein_position	transcript_expression	gene_expression	normal_depth	normal_vaf	tdna_depth	tdna_vaf	trna_depth	trna_vaf	index	protein_length_change
+3	41265565	41266581	TACTCAAGGTTTGTGTCATTAAATCTTTAGTTACTGAATTGGGGCTCTGCTTCGTTGCCATTAAGCCAGTCTGGCTGAGATCCCCCTGCTTTCCTCTCTCCCTGCTTACTTGTCAGGCTACCTTTTGCTCCATTTTCTGCTCACTCCTCCTAATGGCTTGGTGAAATAGCAAACAAGCCACCAGCAGGAATCTAGTCTGGATGACTGCTTCTGGAGCCTGGATGCAGTACCATTCTTCCACTGATTCAGTGAGTAACTGTTAGGTGGTTCCCTAAGGGATTAGGTATTTCATCACTGAGCTAACCCTGGCTATCATTCTGCTTTTCTTGGCTGTCTTTCAGATTTGACTTTATTTCTAAAAATATTTCAATGGGTCATATCACAGATTCTTTTTTTTTAAATTAAAGTAACATTTCCAATCTACTAATGCTAATACTGTTTCGTATTTATAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAGTATTATTTTTCATTGCCTTACTGAAAGTCAGAATGCAGTTTTGAGAACTAAAAAGTTAGTGTATAATAGTTTAAATAAAATGTTGTGGTGAAGAAAAGAGAGTAATAGCAATGTCACTTTTACCATTTAGGATAGCAAATACTTAGGTAAATGCTGAACTGTGGATAGTGAGTGTTGAATTAACCTTTTCCAGATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCT	T	CTNNB1	ENST00000349496	TQGLCH*IFSY*IGALLRCH*ASLAEIPLLSSLPAYLSGYLLLHFLLTPPNGLVK*QTSHQQESSLDDCFWSLDAVPFFH*FSE*LLGGSLRD*VFHH*ANPGYHSAFLGCLSDLTLFLKIFQWVISQILFF*IKVTFPIY*C*YCFVFIADLMELDMAMEPDRKAAVSHWQQQSYLDSGIHSGATTTAPSLSGKGNPEEEDVDTSQVLYEWEQGFSQSFTQEQVAGKSIIFHCLTESQNAVLRTKKLVYNSLNKMLW*RKESNSNVTFTI*DSKYLGKC*TVDSEC*INLFQILMDSMQ*LELRGYELLCSLRH*MRACRSHLHSLMLLIPLMSSVWX/-	ENSG00000168036	MATQADLMELDMAMEPDRKAAVSHWQQQSYLDSGIHSGATTTAPSLSGKGNPEEEDVDTSQVLYEWEQGFSQSFTQEQVADIDGQYAMTRAQRVRAAMFPETLDEGMQIPSTQFDAAHPTNVQRLAEPSQMLKHAVVNLINYQDDAELATRAIPELTKLLNDEDQVVVNKAAVMVHQLSKKEASRHAIMRSPQMVSAIVRTMQNTNDVETARCTAGTLHNLSHHREGLLAIFKSGGIPALVKMLGSPVDSVLFYAITTLHNLLLHQEGAKMAVRLAGGLQKMVALLNKTNVKFLAITTDCLQILAYGNQESKLIILASGGPQALVNIMRTYTYEKLLWTTSRVLKVLSVCSSNKPAIVEAGGMQALGLHLTDPSQRLVQNCLWTLRNLSDAATKQEGMEGLLGTLVQLLGSDDINVVTCAAGILSNLTCNNYKNKMMVCQVGGIEALVRTVLRAGDREDITEPAICALRHLTSRHQEAEMAQNAVRLHYGLPVVVKLLHPPSHWPLIKATVGLIRNLALCPANHAPLREQGAIPRLVQLLVRAHQDTQRRTSMGGTQQQFVEGVRMEEIVEGCTGALHILARDVHNRIVIRGLNTIPLFVQLLYSPIENIQRVAAGVLCELAQDKEAAEAIEAEGATAPLTELLHSRNEGVATYAAAVLFRMSEDKPQDYKKRLSVELTSSLFRTEPMAWNETADLGLDIGAQGEPLGYRQDDPSYRSFHSGGYGQDALGMDPMMEHEMGGHHPGADYPVDGLPDLGHAQDLMDGLPPGDSNQLAWFDTDL			inframe_del	3-126	NA	NA	NA	NA	NA	NA	NA	NA	1.CTNNB1.ENST00000349496.inframe_del.3-126TQGLCH*IFSY*IGALLRCH*ASLAEIPLLSSLPAYLSGYLLLHFLLTPPNGLVK*QTSHQQESSLDDCFWSLDAVPFFH*FSE*LLGGSLRD*VFHH*ANPGYHSAFLGCLSDLTLFLKIFQWVISQILFF*IKVTFPIY*C*YCFVFIADLMELDMAMEPDRKAAVSHWQQQSYLDSGIHSGATTTAPSLSGKGNPEEEDVDTSQVLYEWEQGFSQSFTQEQVAGKSIIFHCLTESQNAVLRTKKLVYNSLNKMLW*RKESNSNVTFTI*DSKYLGKC*TVDSEC*INLFQILMDSMQ*LELRGYELLCSLRH*MRACRSHLHSLMLLIPLMSSVWX/-	

tests/test_fasta_generator.py

@@ -564,6 +564,48 @@ def test_protein_change_with_asterisk_in_wildtype_and_mutant(self):
         self.assertEqual(os.path.getsize(generate_fasta_output_file.name), 0)
         self.assertEqual(os.path.getsize(generate_fasta_key_output_file.name), 0)
 
+    def test_protein_change_with_X_in_wildtype_and_mutatnt(self):
+        peptide_sequence_length        = '21'
+        test_data_dir                  = os.path.join(self.test_data_dir, 'protein_change_with_X_in_wildtype_and_mutant')
+        generate_fasta_input_file      = os.path.join(test_data_dir, 'input.tsv')
+        generate_fasta_output_file     = tempfile.NamedTemporaryFile()
+        generate_fasta_key_output_file = tempfile.NamedTemporaryFile()
+
+        generate_fasta_params = {
+            'input_file'                : generate_fasta_input_file,
+            'peptide_sequence_length'   : self.peptide_sequence_length,
+            'epitope_length'            : self.epitope_length,
+            'output_file'               : generate_fasta_output_file.name,
+            'output_key_file'           : generate_fasta_key_output_file.name,
+            'downstream_sequence_length': None,
+        }
+        generator = FastaGenerator(**generate_fasta_params)
+
+        self.assertFalse(generator.execute())
+        self.assertEqual(os.path.getsize(generate_fasta_output_file.name), 0)
+        self.assertEqual(os.path.getsize(generate_fasta_key_output_file.name), 0)
+
+    def test_protein_change_with_multiple_asterisks(self):
+        peptide_sequence_length        = '21'
+        test_data_dir                  = os.path.join(self.test_data_dir, 'protein_change_with_multiple_asterisks')
+        generate_fasta_input_file      = os.path.join(test_data_dir, 'input.tsv')
+        generate_fasta_output_file     = tempfile.NamedTemporaryFile()
+        generate_fasta_key_output_file = tempfile.NamedTemporaryFile()
+
+        generate_fasta_params = {
+            'input_file'                : generate_fasta_input_file,
+            'peptide_sequence_length'   : self.peptide_sequence_length,
+            'epitope_length'            : self.epitope_length,
+            'output_file'               : generate_fasta_output_file.name,
+            'output_key_file'           : generate_fasta_key_output_file.name,
+            'downstream_sequence_length': None,
+        }
+        generator = FastaGenerator(**generate_fasta_params)
+
+        self.assertFalse(generator.execute())
+        self.assertEqual(os.path.getsize(generate_fasta_output_file.name), 0)
+        self.assertEqual(os.path.getsize(generate_fasta_key_output_file.name), 0)
+
     def test_distance_from_start_works_as_expected(self):
         generate_fasta_input_file      = tempfile.NamedTemporaryFile()
         generate_fasta_output_file     = tempfile.NamedTemporaryFile()