def translate_with_fs(self, frameshifts=None):
# frameshifts is a dict in {pos: Variant} form. NOT VariantSet! We are translating
# with a particular FS combination and NOT calculating possible combinations here.
if frameshifts is None:
frameshifts = []
else:
frameshifts = sorted(frameshifts) # should be already sorted, but...
# the number of bases gained or lost by each frameshift. Positive: gain, negative: lost
fs_shifts = [(fpos, fpos[0] - fpos[1] + len(fsvar)) for
fpos, fsvar in frameshifts]
def reposition(orig_pos):
start, stop = orig_pos
new_start, new_stop = start, stop
for (fs_start, fs_stop), fs_shift in fs_shifts:
if fs_start <= start < fs_stop or fs_start < stop <= fs_stop:
warnings.warn('Watch out, variant inside frameshift! We\'re not ready to handle '
'that yet. %s, (%d-%d)' % (self.id, fs_start, fs_stop))
if start >= fs_stop: # frameshift happened before variant, so variant shifts
new_start += fs_shift
new_stop += fs_shift
return new_start, new_stop
fs_positions = []
new_seq = Seq('', generic_nucleotide)
original_seq = self.sequence[self.cds[0]:]
next_start = 0
for (fs_start, fs_stop), fs_var in frameshifts:
new_seq += original_seq[next_start:fs_start]
fs_positions.append(len(new_seq)/3) # register first AA position that current FS affects
new_seq += fs_var.sequence
next_start = fs_stop
else:
new_seq += original_seq[next_start:]
protein = Protein(new_seq.translate(), self)
# now with the new sequence created it's time to translate non-FS variants. Since the frameshifts
# moved their relative positions around, we have to use their updated locations.
new_variantsets = {}
for (start, stop), vset in {reposition(vpos): vset for vpos, vset in self.variantsets.iteritems()}.iteritems():
cstart = start - (start % 3) # codon start
cstop = (stop + 2) / 3 * 3 # codon stop
new_vset = VariantSet(vset.genomic_pos, set([]))
# TODO: this may introduce superfluous AA-s, that is 'Q'->'QP' when a
# ''->'P' would be enough. Need to look into it. -- 99% SOLVED.
for v in vset:
if v.variant_type not in ('FSI', 'FSD'):
aa_seq = (new_seq[cstart:start] + v.sequence + new_seq[stop:cstop]).translate()
translated_variant = Variant(v.genomic_pos, v.variant_type, aa_seq, 'AA', v.sample_id)
# TODO: should we carry over metadata? I think we really should!
# for now, let's just keep a simple reference to the original variant
translated_variant.log_metadata('origin', v)
new_vset.add_variant(translated_variant)
new_vset.log_metadata('origin', vset) # TODO: maybe origin should be a first-class attribue not metadata?
if len(new_vset) > 0: # frameshift VariantSets would create empty new_vsets, disregard them
new_variantsets[(cstart/3, cstop/3)] = new_vset
protein.variantsets = new_variantsets
protein._trim_after_stop()
# now let's see which frameshifts were actually kept. As induced stop codons may have terminated
# the translated sequence, there's a chance that later frameshifts are irrelevant.
# <= instead of < as the stop codon (Biopython '*') is trimmed away and if a FS induces that
# as its first affected AA position it DID play a role in what the sequence has become
# although '*' is not part of the protein sequence itself.
fs_positions = filter(lambda x: x<=len(protein), fs_positions)
used_frameshifts = zip(fs_positions, (fs for _, fs in frameshifts[:len(fs_positions)]))
assert protein.get_metadata('frameshifts') == [], ("Someone has tweaked with the 'frameshift'"
" field of protein metadata before. May have come from inherited transcript metadata."
" Use a different field name in your custom functions.")
protein.log_metadata('frameshifts', used_frameshifts)
return protein
