Support for wildcards lost in the newer versions of hgvs?

[melissacline]

One of the engineers on my team noticed that he updated hgvs recently, and after the update we somehow lost the ability to parse cDNA variants with indeterminate nucleotides. Was this by design?

(the message was copied from our project slack board, and sorry if the formatting looks funny. The original is here).

From Marc:

here one of the variants I've mentioned on the call where the conversion to protein fails with newer versions of hgvs (newer than 1.3.0 I believe)

print(parser,(url) assembly_mapper)
cdna = parser.parse('NM_000059.3:c.2339C>R')
assembly_mapper.c_to_p(cdna)

gives:

KeyError                                  Traceback (most recent call last)
~/software/anaconda/envs/brca_pipeline_py3/lib/python3.8/site-packages/bioutils/sequences.py in translate_cds(seq, full_codons, ter_symbol)
    443         try:
--> 444             aa = dna_to_aa1_lut[seq[i:i + 3]]
    445         except KeyError:
KeyError: 'TRA'
During handling of the above exception, another exception occurred:
ValueError                                Traceback (most recent call last)
<ipython-input-31-0172ec91a9d8> in <module>
      1 print(parser, assembly_mapper)
      2 cdna = parser.parse('NM_000059.3:c.2339C>R')
----> 3 assembly_mapper.c_to_p(cdna)
~/software/anaconda/envs/brca_pipeline_py3/lib/python3.8/site-packages/hgvs/assemblymapper.py in c_to_p(self, var_c)
    156 
    157     def c_to_p(self, var_c):
--> 158         var_out = super(AssemblyMapper, self).c_to_p(var_c)
    159         return self._maybe_normalize(var_out)
    160 
~/software/anaconda/envs/brca_pipeline_py3/lib/python3.8/site-packages/hgvs/variantmapper.py in c_to_p(self, var_c, pro_ac)
    402         # currently get list of 1 element loop structure implemented
    403         # to handle this, but doesn't really do anything currently.
--> 404         all_alt_data = builder.build_altseq()
    405 
    406         var_ps = []
~/software/anaconda/envs/brca_pipeline_py3/lib/python3.8/site-packages/hgvs/utils/altseqbuilder.py in build_altseq(self)
    158 
    159         try:
--> 160             this_alt_data = type_map[edit_type]()
    161         except KeyError:
    162             raise NotImplementedError("c to p translation unsupported for {} type {}".format(
~/software/anaconda/envs/brca_pipeline_py3/lib/python3.8/site-packages/hgvs/utils/altseqbuilder.py in _incorporate_delins(self)
    235         variant_start_aa = max(int(math.ceil((self._var_c.posedit.pos.start.base) / 3.0)), 1)
    236 
--> 237         alt_data = AltTranscriptData(
    238             seq,
    239             cds_start,
~/software/anaconda/envs/brca_pipeline_py3/lib/python3.8/site-packages/hgvs/utils/altseqbuilder.py in __init__(self, seq, cds_start, cds_stop, is_frameshift, variant_start_aa, accession, is_substitution, is_ambiguous)
     59             seq_cds = seq[cds_start - 1:]
     60             seq_cds = ''.join(seq_cds)
---> 61             seq_aa = translate_cds(seq_cds, full_codons=False, ter_symbol="X")
     62             stop_pos = seq_aa[:(cds_stop - cds_start + 1) // 3].rfind("*")
     63             if stop_pos == -1:
~/software/anaconda/envs/brca_pipeline_py3/lib/python3.8/site-packages/bioutils/sequences.py in translate_cds(seq, full_codons, ter_symbol)
    444             aa = dna_to_aa1_lut[seq[i:i + 3]]
    445         except KeyError:
--> 446             raise ValueError("Codon {} at position {}..{} is undefined in codon table".format(
    447                 seq[i:i + 3], i+1, i+3))
    448         protein_seq.append(aa)
ValueError: Codon TRA at position 2338..2340 is undefined in codon table
---------------------------------------------------------------------------
KeyError                                  Traceback (most recent call last)
~/software/anaconda/envs/brca_pipeline_py3/lib/python3.8/site-packages/bioutils/sequences.py in translate_cds(seq, full_codons, ter_symbol)
    443         try:
--> 444             aa = dna_to_aa1_lut[seq[i:i + 3]]
    445         except KeyError:
KeyError: 'TRA'
During handling of the above exception, another exception occurred:
ValueError                                Traceback (most recent call last)
<ipython-input-31-0172ec91a9d8> in <module>
      1 print(parser, assembly_mapper)
      2 cdna = parser.parse('NM_000059.3:c.2339C>R')
----> 3 assembly_mapper.c_to_p(cdna)
~/software/anaconda/envs/brca_pipeline_py3/lib/python3.8/site-packages/hgvs/assemblymapper.py in c_to_p(self, var_c)
    156 
    157     def c_to_p(self, var_c):
--> 158         var_out = super(AssemblyMapper, self).c_to_p(var_c)
    159         return self._maybe_normalize(var_out)
    160 
~/software/anaconda/envs/brca_pipeline_py3/lib/python3.8/site-packages/hgvs/variantmapper.py in c_to_p(self, var_c, pro_ac)
    402         # currently get list of 1 element loop structure implemented
    403         # to handle this, but doesn't really do anything currently.
--> 404         all_alt_data = builder.build_altseq()
    405 
    406         var_ps = []
~/software/anaconda/envs/brca_pipeline_py3/lib/python3.8/site-packages/hgvs/utils/altseqbuilder.py in build_altseq(self)
    158 
    159         try:
--> 160             this_alt_data = type_map[edit_type]()
    161         except KeyError:
    162             raise NotImplementedError("c to p translation unsupported for {} type {}".format(
~/software/anaconda/envs/brca_pipeline_py3/lib/python3.8/site-packages/hgvs/utils/altseqbuilder.py in _incorporate_delins(self)
    235         variant_start_aa = max(int(math.ceil((self._var_c.posedit.pos.start.base) / 3.0)), 1)
    236 
--> 237         alt_data = AltTranscriptData(
    238             seq,
    239             cds_start,
~/software/anaconda/envs/brca_pipeline_py3/lib/python3.8/site-packages/hgvs/utils/altseqbuilder.py in __init__(self, seq, cds_start, cds_stop, is_frameshift, variant_start_aa, accession, is_substitution, is_ambiguous)
     59             seq_cds = seq[cds_start - 1:]
     60             seq_cds = ''.join(seq_cds)
---> 61             seq_aa = translate_cds(seq_cds, full_codons=False, ter_symbol="X")
     62             stop_pos = seq_aa[:(cds_stop - cds_start + 1) // 3].rfind("*")
     63             if stop_pos == -1:
~/software/anaconda/envs/brca_pipeline_py3/lib/python3.8/site-packages/bioutils/sequences.py in translate_cds(seq, full_codons, ter_symbol)
    444             aa = dna_to_aa1_lut[seq[i:i + 3]]
    445         except KeyError:
--> 446             raise ValueError("Codon {} at position {}..{} is undefined in codon table".format(
    447                 seq[i:i + 3], i+1, i+3))
    448         protein_seq.append(aa)
ValueError: Codon TRA at position 2338..2340 is undefined in codon table"

[reece]

Confirmed. Rats.

#527, released in hgvs 1.4, eliminated the dependency on biopython which was used solely for the translate function.

The replacement translate function doesn't support degenerate codons. The lookup table is here:
https://github.com/biocommons/bioutils/blob/master/src/bioutils/sequences.py#L40

See biocommons/bioutils#29.