def AlignExhaustive(seq_wobble,
seq_cds,
seq_peptide,
map_p2c,
options,
diag_width=2):
"""Align two sequences.
Align in chunks to keep memory low. Both sequences are roughly the same,
thus align only in diagonal.
"""
gop, gep = -1.0, -1.0
matrix = alignlib_lite.py_makeSubstitutionMatrixBackTranslation(
1, -10, 1, alignlib_lite.py_getDefaultEncoder())
alignlib_lite.py_setDefaultSubstitutionMatrix(matrix)
if seq_wobble.getLength() < 10000:
if options.loglevel >= 6:
options.stdlog.write("# using full dynamic programing matrix.\n")
options.stdlog.flush()
# do not penalize gaps at the end, because sometimes the last codon
# might be missing
alignator = alignlib_lite.py_makeAlignatorDPFull(
alignlib_lite.py_ALIGNMENT_GLOBAL, gop, gep, 1, 1)
else:
diag_width = abs(seq_wobble.getLength() - seq_cds.getLength()) + 1
if options.loglevel >= 6:
options.stdlog.write("# using dot alignment with diagonal %i\n" %
diag_width)
options.stdlog.flush()
dots = alignlib_lite.py_makeAlignmentMatrixRow()
for x in range(0, seq_wobble.getLength()):
xr = seq_wobble.asResidue(x)
for y in range(max(0, x - diag_width),
min(seq_cds.getLength(), x + diag_width)):
s = matrix.getValue(xr, seq_cds.asResidue(y))
if s >= 0:
dots.addPair(x, y, float(s))
if options.loglevel >= 6:
options.stdlog.write("# finished adding %i dots" %
dots.getLength())
options.stdlog.flush()
alignator_dummy = alignlib_lite.py_makeAlignatorPrebuilt(dots)
alignator = alignlib_lite.py_makeAlignatorDots(alignator_dummy, gop,
gep)
alignator.align(map_p2c, seq_wobble, seq_cds)
def AlignExhaustive(seq_wobble, seq_cds, seq_peptide, map_p2c,
options,
diag_width=2):
"""Align two sequences.
Align in chunks to keep memory low. Both sequences are roughly the same,
thus align only in diagonal.
"""
gop, gep = -1.0, -1.0
matrix = alignlib_lite.py_makeSubstitutionMatrixBackTranslation(
1, -10, 1, alignlib_lite.py_getDefaultEncoder())
alignlib_lite.py_setDefaultSubstitutionMatrix(matrix)
if seq_wobble.getLength() < 10000:
if options.loglevel >= 6:
options.stdlog.write("# using full dynamic programing matrix.\n")
options.stdlog.flush()
# do not penalize gaps at the end, because sometimes the last codon
# might be missing
alignator = alignlib_lite.py_makeAlignatorDPFull(
alignlib_lite.py_ALIGNMENT_GLOBAL, gop, gep, 1, 1)
else:
diag_width = abs(seq_wobble.getLength() - seq_cds.getLength()) + 1
if options.loglevel >= 6:
options.stdlog.write(
"# using dot alignment with diagonal %i\n" % diag_width)
options.stdlog.flush()
dots = alignlib_lite.py_makeAlignmentMatrixRow()
for x in range(0, seq_wobble.getLength()):
xr = seq_wobble.asResidue(x)
for y in range(max(0, x - diag_width),
min(seq_cds.getLength(),
x + diag_width)):
s = matrix.getValue(xr, seq_cds.asResidue(y))
if s >= 0:
dots.addPair(x, y, float(s))
if options.loglevel >= 6:
options.stdlog.write(
"# finished adding %i dots" % dots.getLength())
options.stdlog.flush()
alignator_dummy = alignlib_lite.py_makeAlignatorPrebuilt(dots)
alignator = alignlib_lite.py_makeAlignatorDots(
alignator_dummy, gop, gep)
alignator.align(map_p2c, seq_wobble, seq_cds)
def AlignCodonBased( seq_wobble, seq_cds, seq_peptide, map_p2c, options,
diag_width = 2, max_advance = 2 ):
"""advance in codons in seq_wobble and match to nucleotides in seq_cds.
Due to alinglib this is all in one-based coordinates.
Takes care of frameshifts.
"""
map_p2c.clear()
gop, gep = -1.0, -1.0
matrix = alignlib_lite.py_makeSubstitutionMatrixBackTranslation( 1, -10, 1, alignlib_lite.py_getDefaultEncoder() )
pep_seq = seq_peptide.asString()
cds_seq = seq_cds.asString()
wobble_seq = seq_wobble.asString()
lcds = seq_cds.getLength()
lwobble = seq_wobble.getLength()
y = 0
x = 0
last_start = None
while x < lwobble and y < lcds:
xr = seq_wobble.asResidue( x )
# skip over masked chars in wobble - these are gaps
if seq_wobble.asChar(x) == "X":
x += 1
continue
# skip over masked chars in wobble - these are from
# masked chars in the peptide sequence
# Note to self: do not see all implications of this change
# check later.
if seq_wobble.asChar(x) == "N":
x += 1
continue
# skip over gaps in wobble
if seq_wobble.asChar(x) == "-":
x += 1
continue
s = matrix.getValue( xr, seq_cds.asResidue(y) )
if options.loglevel >= 6:
if (x % 3 == 0):
c = seq_cds.asChar(y) + seq_cds.asChar(y+1) + seq_cds.asChar(y+2)
options.stdlog.write( "# c=%s, x=%i, y=%i, aa=%s target=%s\n" % (c, x, y,
Genomics.MapCodon2AA( c ),
pep_seq[int(x/3)]) )
options.stdlog.write( "# x=%i\twob=%s\ty=%i\tcds=%s\txr=%s\tcds=%i\tscore=%s\n" % \
(x, seq_wobble.asChar(x), y, seq_cds.asChar(y), xr, seq_cds.asResidue(y), str(s) ))
# deal with mismatches
if s <= 0:
tmp_map_p2c = alignlib_lite.py_makeAlignmentVector()
## backtrack to previous three codons and align
## three codons for double frameshifts that span two codons and
## produce two X's and six WWWWWW.
## number of nucleotides to extend (should be multiple of 3)
## less than 12 caused failure for some peptides.
d = 15
# extend by amound dx
dx = (x % 3) + d
x_start = max(0, x - dx )
# map to ensure that no ambiguous residue mappings
# exist after re-alignment
y_start = max(0, map_p2c.mapRowToCol( x_start, alignlib_lite.py_RIGHT ))
if (x_start, y_start) == last_start:
raise ValueError( "infinite loop detected" )
last_start = (x_start, y_start)
x_end = min(x_start + 2 * d, len(wobble_seq) )
y_end = min(y_start + 2 * d, len(cds_seq) )
wobble_fragment = alignlib_lite.py_makeSequence(wobble_seq[x_start:x_end])
cds_fragment = alignlib_lite.py_makeSequence(cds_seq[y_start:y_end])
AlignExhaustive( wobble_fragment, cds_fragment, "", tmp_map_p2c, options )
if options.loglevel >= 10:
options.stdlog.write("# fragmented alignment from %i-%i, %i-%i:\n%s\n" % (x_start, x_end,
y_start, y_end,
str(alignlib_lite.py_AlignmentFormatExplicit( tmp_map_p2c,
wobble_fragment,
cds_fragment ))))
options.stdlog.flush()
## clear alignment
map_p2c.removeRowRegion( x_start, x_end )
ngap = 0
last_x, last_y = None, None
for xxx in range( tmp_map_p2c.getRowFrom(), tmp_map_p2c.getRowTo() ):
yyy = tmp_map_p2c.mapRowToCol(xxx)
if yyy >= 0:
x = xxx + x_start
y = yyy + y_start
xr = seq_wobble.asResidue(x)
s = matrix.getValue( seq_wobble.asResidue(x), seq_cds.asResidue(y) )
if s < 0:
raise ValueError("mismatched residue wobble: %i (%s), cds: %i (%s)" % (x, seq_wobble.asChar(x), y, seq_cds.asChar(y)))
map_p2c.addPair( x, y, s)
last_x, last_y = x, y
if options.loglevel >= 6:
options.stdlog.write( "# reset: x=%i\twob=%s\ty=%i\tcds=%s\txr=%s\tcds=%i\tscore=%i\n" % \
(x, seq_wobble.asChar(x), y, seq_cds.asChar(y), xr, seq_cds.asResidue(y), s ))
options.stdlog.flush()
ngap = 0
else:
ngap += 1
# treat special case of double frameshifts. They might cause a petide/wobble residue
# to be eliminated and thus the translated sequences will differ.
# simply delete the last residue between x and y and move to next codon.
if ngap == 3:
map_p2c.removeRowRegion( last_x, last_x + 1 )
last_x += 1
map_p2c.addPair( last_x, last_y )
if options.loglevel >= 6:
options.stdlog.write( "# double: x=%i\twob=%s\ty=%i\tcds=%s\txr=%s\tcds=%i\tscore=%i\n" % \
(last_x, seq_wobble.asChar(last_x), last_y, seq_cds.asChar(last_y), xr, seq_cds.asResidue(last_y), s ))
options.stdlog.flush()
ngap = 0
## exit condition if alignment is shorter than problematic residue
## need to catch this to avoid infinite loop.
if tmp_map_p2c.getRowTo() < d:
if lwobble - x <= 4:
## only last codon is missing, so ok
break
else:
raise ValueError("failure to align in designated window.")
s = 0
s = matrix.getValue( xr, seq_cds.asResidue(y) )
if s < 0:
raise ValueError("mis-matching residues.")
map_p2c.addPair( x, y, float(s) )
# advance to next residues
x += 1
y += 1
# sanity checks
assert( map_p2c.getRowTo() <= seq_wobble.getLength() )
assert( map_p2c.getColTo() <= seq_cds.getLength() )
def AlignCodonBased(seq_wobble,
seq_cds,
seq_peptide,
map_p2c,
options,
diag_width=2,
max_advance=2):
"""advance in codons in seq_wobble and match to nucleotides in seq_cds.
Due to alinglib this is all in one-based coordinates.
Takes care of frameshifts.
"""
map_p2c.clear()
gop, gep = -1.0, -1.0
matrix = alignlib_lite.py_makeSubstitutionMatrixBackTranslation(
1, -10, 1, alignlib_lite.py_getDefaultEncoder())
pep_seq = seq_peptide.asString()
cds_seq = seq_cds.asString()
wobble_seq = seq_wobble.asString()
lcds = seq_cds.getLength()
lwobble = seq_wobble.getLength()
y = 0
x = 0
last_start = None
while x < lwobble and y < lcds:
xr = seq_wobble.asResidue(x)
# skip over masked chars in wobble - these are gaps
if seq_wobble.asChar(x) == "X":
x += 1
continue
# skip over masked chars in wobble - these are from
# masked chars in the peptide sequence
# Note to self: do not see all implications of this change
# check later.
if seq_wobble.asChar(x) == "N":
x += 1
continue
# skip over gaps in wobble
if seq_wobble.asChar(x) == "-":
x += 1
continue
s = matrix.getValue(xr, seq_cds.asResidue(y))
if options.loglevel >= 6:
if (x % 3 == 0):
c = seq_cds.asChar(y) + seq_cds.asChar(y +
1) + seq_cds.asChar(y +
2)
options.stdlog.write(
"# c=%s, x=%i, y=%i, aa=%s target=%s\n" %
(c, x, y, Genomics.MapCodon2AA(c), pep_seq[int(x / 3)]))
options.stdlog.write(
"# x=%i\twob=%s\ty=%i\tcds=%s\txr=%s\tcds=%i\tscore=%s\n" %
(x, seq_wobble.asChar(x), y, seq_cds.asChar(y), xr,
seq_cds.asResidue(y), str(s)))
# deal with mismatches
if s <= 0:
tmp_map_p2c = alignlib_lite.py_makeAlignmentVector()
# backtrack to previous three codons and align
# three codons for double frameshifts that span two codons and
# produce two X's and six WWWWWW.
# number of nucleotides to extend (should be multiple of 3)
# less than 12 caused failure for some peptides.
d = 15
# extend by amound dx
dx = (x % 3) + d
x_start = max(0, x - dx)
# map to ensure that no ambiguous residue mappings
# exist after re-alignment
y_start = max(0,
map_p2c.mapRowToCol(x_start, alignlib_lite.py_RIGHT))
if (x_start, y_start) == last_start:
raise ValueError("infinite loop detected")
last_start = (x_start, y_start)
x_end = min(x_start + 2 * d, len(wobble_seq))
y_end = min(y_start + 2 * d, len(cds_seq))
wobble_fragment = alignlib_lite.py_makeSequence(
wobble_seq[x_start:x_end])
cds_fragment = alignlib_lite.py_makeSequence(
cds_seq[y_start:y_end])
AlignExhaustive(wobble_fragment, cds_fragment, "", tmp_map_p2c,
options)
if options.loglevel >= 10:
options.stdlog.write(
"# fragmented alignment from %i-%i, %i-%i:\n%s\n" %
(x_start, x_end, y_start, y_end,
str(
alignlib_lite.py_AlignmentFormatExplicit(
tmp_map_p2c, wobble_fragment, cds_fragment))))
options.stdlog.flush()
# clear alignment
map_p2c.removeRowRegion(x_start, x_end)
ngap = 0
last_x, last_y = None, None
for xxx in range(tmp_map_p2c.getRowFrom(), tmp_map_p2c.getRowTo()):
yyy = tmp_map_p2c.mapRowToCol(xxx)
if yyy >= 0:
x = xxx + x_start
y = yyy + y_start
xr = seq_wobble.asResidue(x)
s = matrix.getValue(seq_wobble.asResidue(x),
seq_cds.asResidue(y))
if s < 0:
raise ValueError(
"mismatched residue wobble: %i (%s), cds: %i (%s)"
% (x, seq_wobble.asChar(x), y, seq_cds.asChar(y)))
map_p2c.addPair(x, y, s)
last_x, last_y = x, y
if options.loglevel >= 6:
options.stdlog.write(
"# reset: x=%i\twob=%s\ty=%i\tcds=%s\txr=%s\tcds=%i\tscore=%i\n"
% (x, seq_wobble.asChar(x), y, seq_cds.asChar(y),
xr, seq_cds.asResidue(y), s))
options.stdlog.flush()
ngap = 0
else:
ngap += 1
# treat special case of double frameshifts. They might cause a petide/wobble residue
# to be eliminated and thus the translated sequences will differ.
# simply delete the last residue between x and y and move to
# next codon.
if ngap == 3:
map_p2c.removeRowRegion(last_x, last_x + 1)
last_x += 1
map_p2c.addPair(last_x, last_y)
if options.loglevel >= 6:
options.stdlog.write(
"# double: x=%i\twob=%s\ty=%i\tcds=%s\txr=%s\tcds=%i\tscore=%i\n"
% (last_x, seq_wobble.asChar(last_x), last_y,
seq_cds.asChar(last_y), xr,
seq_cds.asResidue(last_y), s))
options.stdlog.flush()
ngap = 0
# exit condition if alignment is shorter than problematic residue
# need to catch this to avoid infinite loop.
if tmp_map_p2c.getRowTo() < d:
if lwobble - x <= 4:
# only last codon is missing, so ok
break
else:
raise ValueError("failure to align in designated window.")
s = 0
s = matrix.getValue(xr, seq_cds.asResidue(y))
if s < 0:
raise ValueError("mis-matching residues.")
map_p2c.addPair(x, y, float(s))
# advance to next residues
x += 1
y += 1
# sanity checks
assert (map_p2c.getRowTo() <= seq_wobble.getLength())
assert (map_p2c.getColTo() <= seq_cds.getLength())
