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alignlib.py
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alignlib.py
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#
# alignlib.py
# Sequence and alignment functions
#
# python libs
import sys
from collections import defaultdict
# rasmus libs
from rasmus import util
# compbio libs
from . import fasta, seqlib
from seqlib import *
#=============================================================================
# Alignment functions
def new_align(aln=None):
"""Makes a new alignment object based on the given object
given return
----- ------
dict FastaDict
other other
"""
if aln is None:
return fasta.FastaDict()
elif isinstance(aln, SeqDict):
return type(aln)()
else:
return fasta.FastaDict()
def mapalign(aln, keyfunc=lambda x: x, valfunc=lambda x: x):
"""Maps the keys and values of an alignment"""
aln2 = new_align(aln)
for key, val in aln.iteritems():
aln2[keyfunc(key)] = valfunc(val)
return aln2
def subalign(aln, cols):
"""Returns an alignment with a subset of the columns (cols)"""
return mapalign(aln, valfunc=lambda x: "".join(util.mget(x, cols)))
def remove_empty_columns(aln, enforce_codon=False):
"""
Removes any column from an alignment 'aln' that contains only gaps
if enforce_codon, only removes empty columns if they correspond to an empty codon position
A new alignment is returned
"""
ind = []
seqs = aln.values()
alnlen = aln.alignlen()
if not enforce_codon:
for i in range(alnlen):
for seq in seqs:
if seq[i] != "-":
ind.append(i)
break
else:
if alnlen % 3 != 0:
raise Exception("cannot set enforce_codon if alignment length is not a multiple of three")
for i in range(0, alnlen, 3):
for seq in seqs:
if seq[i:i+3] != "---":
ind.extend([i,i+1,i+2])
break
return subalign(aln, ind)
def remove_gapped_columns(aln):
"""Removes any column form an alignment 'aln' that contains a gap
A new alignment is returned
"""
cols = zip(* aln.values())
ind = util.find(lambda col: "-" not in col, cols)
return subalign(aln, ind)
def require_nseqs(aln, n):
"""
Keep only columns with atleast 'n' non gapped sequences
"""
seqs = aln.values()
ind = [i for i in range(aln.alignlen())
if sum(1 for seq in seqs if seq[i] != "-") >= n]
return subalign(aln, ind)
def get_seq_overlap(seq1, seq2):
"""
Count number of overlapping bases between two gapped sequences
"""
overlap = 0
for i in range(len(seq1)):
if seq1[i] != "-" and seq2[i] != "-":
overlap += 1
return overlap
def calc_conservation_string(aln):
"""Returns a string of stars representing the conservation of an alignment"""
percids = calc_conservation(aln)
# find identity positions
identity = ""
for pid in percids:
if pid == 1:
identity += "*"
elif pid > .5:
identity += "."
else:
identity += " "
return identity
def calc_conservation(aln):
"""Returns a list of percent matching in each column of an alignment"""
length = len(aln.values()[0])
seqs = aln.values()
percids = []
# find identity positions
identity = ""
for i in xrange(length):
chars = util.hist_dict(util.cget(seqs, i))
if "-" in chars: del chars["-"]
if len(chars) == 0:
percids.append(0.0)
else:
pid = max(chars.values()) / float(len(aln))
percids.append(pid)
return percids
def print_align(aln, seqwidth = 59, spacing=2, extra=fasta.FastaDict(),
out=sys.stdout, order=None):
"""Pretty print an alignment"""
if order == None:
order = aln.keys()
namewidth = max(map(len, order)) + spacing
def mkname(name, namewidth):
name2 = name[:namewidth]
name2 += " " * (namewidth - len(name2))
return name2
identity = calc_conservation_string(aln)
# print alignment
for i in xrange(0, len(aln.values()[0]), seqwidth):
# print sequences
for name in order:
print >>out, "%s %s" % (mkname(name, namewidth),
aln[name][i:i+seqwidth])
# print extra
for name in extra.keys():
print >>out, "%s %s" % (mkname(name, namewidth),
extra[name][i:i+seqwidth])
# print identity
print >>out, (" "*namewidth) + " " + identity[i:i+seqwidth]
print >>out
def revtranslate_align(aaseqs, dnaseqs, check=False, trim=False):
"""Reverse translates aminoacid alignment into DNA alignment
Must supply original ungapped DNA.
"""
align = new_align(aaseqs)
for name, seq in aaseqs.iteritems():
try:
dna = dnaseqs[name].upper()
dnalen = len(dna)
aalen = sum(int(a != "-") for a in seq)
if len(dna) != aalen * 3:
if trim:
# make dna a multiple of three
dna = dna[:(len(dna) // 3) * 3]
if len(dna) > aalen * 3:
# trim dna
dna = dna[:aalen*3]
else:
# trim peptide to match nucleotide
j = 0
for i in xrange(len(seq)):
if seq[i] != '-':
j += 1
if j > len(dna) // 3:
seq = seq[:i] + "-" * (len(seq) - i)
break
aalen2 = sum(int(a != "-") for a in seq)
assert len(dna) == aalen2 * 3, (
len(dna), aalen2 * 3)
util.logger("trim dna (%d) and pep (%d)" %
(dnalen - len(dna), aalen - aalen2))
else:
# is last residue X?
for i in xrange(len(seq)-1, -1, -1):
if seq[i] == "-":
continue
if seq[i] == "X":
# repair
seq = seq[:i] + "-" * (len(seq)-i)
dna = dna[:-3] #-(len(dna) % 3)]
break
align[name] = revtranslate(seq, dna, check=check)
except TranslateError, e:
raise
return align
#=============================================================================
# four fold degeneracy
def mark_codon_pos(seq, pos=0):
"""
return the codon position for each base in a gapped sequence
codon
ATG
012
gaps are given codon pos -1
Ns are counted as bases
"""
codons = []
for base in seq:
if base != "-":
codons.append(pos)
pos = (pos + 1) % 3
else:
codons.append(-1)
return codons
def make_codon_pos_align(aln):
"""Get the codon position of every base in an alignment"""
def func(seq):
dct = {-1: "-",
0: "0",
1: "1",
2: "2"}
return "".join(util.mget(dct, mark_codon_pos(seq)))
return mapalign(aln, valfunc=func)
def find_aligned_codons(aln):
"""Returns the columns indices of the alignment that represent aligned
codons.
"""
ind = range(aln.alignlen())
# throw out codons with non mod 3 gaps
ind2 = []
for i in range(0, aln.alignlen(), 3):
bad = False
for key, val in aln.iteritems():
codon = val[i:i+3]
if "-" in codon and codon != "---":
bad = True
break
if not bad:
ind2.extend([i, i+1, i+2])
return ind2
def filter_aligned_codons(aln):
"""filters an alignment for only aligned codons"""
ind = find_align_codons(aln)
return subalign(aln, ind)
def find_four_fold(aln):
"""Returns index of all columns in alignment that are completely
fourfold degenerate
Assumes that columns are already filtered for aligned codons
"""
# create peptide alignment
pepAln = mapalign(aln, valfunc=translate)
# find peptide conservation
pepcons = []
pep = []
for i in xrange(pepAln.alignlen()):
# get a column from the peptide alignment
col = [seq[i] for seq in pepAln.itervalues()]
# compute the histogram of the column.
# ignore gaps '-' and non-translated 'X'
hist = util.hist_dict(col)
if "-" in hist:
del hist["-"]
if "X" in hist:
del hist["X"]
# column is conserved if only one AA appears
if len(hist) == 1:
pepcons.append(True)
pep.append(hist.keys()[0])
else:
pepcons.append(False)
pep.append("X")
# find four-fold sites in conserved peptides
ind = []
for i in range(0, len(aln.values()[0]), 3):
# process only those columns that are conserved at the peptide level
if pepcons[i//3]:
degen = AA_DEGEN[pep[i//3]]
for j in range(3):
if degen[j] == 4:
ind.append(i+j)
return ind
def filter_four_fold(aln):
"""returns an alignment of only four-fold degenerate sites from an
alignment of coding sequences
This function performs the following steps:
1. remove all codon columns that don't have 0 or 3 gaps
2. keep all codon columns that code for identical AA
3. if the codon column codes for a 4D AA, then keep its 3rd position
"""
aln_codons = filter_align_codons(aln)
ind = find_four_fold(aln_codons)
return subalign(aln_codons, ind)
def calc_four_fold_dist_matrix(aln):
names = aln.keys()
mat = []
# calc upper triangular
for i in range(len(names)):
mat.append([0.0] * (i+1))
for j in range(i+1, len(names)):
ind = find_four_fold(aln.get([names[i], names[j]]))
mismatches = 0
for k in ind:
if aln[names[i]][k] != aln[names[j]][k]:
mismatches += 1
if len(ind) == 0:
mat[-1].append(1.0)
else:
mat[-1].append(mismatches / float(len(ind)))
# make symmetric
for j in range(len(names)):
for i in range(j):
mat[j][i] = mat[i][j]
return mat
def find_degen(aln):
"""Determine the degeneracy of each column in an alignment"""
codon_ind = find_align_codons(aln)
aln2 = subalign(aln, codon_ind)
pep_aln = mapalign(aln2, valfunc=translate)
pep = pep_aln.values()[0]
identies = calc_conservation(pep_aln)
degens = [-1] * aln.alignlen()
for i in range(0, len(codon_ind), 3):
if pep[i/3] == "X":
continue
degen = AA_DEGEN[pep[i/3]]
if identies[i/3] == 1.0:
for j in range(3):
degens[codon_ind[i+j]] = degen[j]
return degens
def make_degen_str(aln):
"""Returns a string containing the degeneracy for each column
in an alignment
"""
degens = find_degen(aln)
degenmap = {-1: " ",
0: "0",
1: "1",
2: "2",
3: "3",
4: "4"}
return "".join(util.mget(degenmap, degens))
def print_degen(aln, **args):
"""Pretty print an alignment with its degeneracy for each column"""
extra = fasta.FastaDict()
extra["DEGEN"] = make_degen_str(aln)
print_align(aln, extra=extra, **args)
#=============================================================================
# background frequency
#
def compute_bgfreq(aln):
# initialize with pseudo counts
dna2int = {'A': 0, "C": 1, "G": 2, "T": 3}
bgfreq = [1,1,1,1]
count = 4
# count
for name, seq in aln.iteritems():
for c in seq.upper():
count += 1
if c in dna2int:
bgfreq[dna2int[c]] += 1
# normalize
bgfreq = [float(freq)/count for freq in bgfreq]
return bgfreq
# Position Specific Scoring Matrix (PSSM)
def align2pssm(aln, pseudocounts = {}):
pssm = []
denom = float(len(aln)) + sum(pseudocounts.values())
for i in xrange(aln.alignlen()):
freqs = defaultdict(lambda: 0)
for j in xrange(len(aln)):
freqs[aln[j][i]] += 1
for key in pseudocounts:
freqs[key] += pseudocounts[key]
for key in freqs:
freqs[key] = math.log(freqs[key] / denom, 2)
pssm.append(freqs)
return pssm
def pssmSeq(pssm, seq):
score = 0.0
for i in xrange(len(seq)):
score += pssm[i][seq[i]]
return score
#=============================================================================
# Coordinate conversions
#
# Coordinate systems
#
# 1. local
# 01234567
# ATGCTGCG
#
# 2. align
# 012222345567
# ATG---CTG-CG
#
# 3. global
# coordinate on chromosome on positive strand
#
# There should only be two kinds of indexing
# 1. 0-based, end exclusive (local/align coordinates)
# 2. 1-based, end inclusive (global coordinates)
#
class CoordConverter (object):
"""Converts between coordinate systems on a gapped sequence"""
def __init__(self, seq):
self.local2alignLookup = local2align(seq)
self.align2localLookup = align2local(seq)
def local2align(self, i, clamp=False):
if clamp:
return self.local2alignLookup[int(util.clamp(i, 0,
len(self.local2alignLookup)-1))]
else:
return self.local2alignLookup[i]
def align2local(self, i, clamp=False):
if clamp:
return self.align2localLookup[int(util.clamp(i, 0,
len(self.align2localLookup)-1))]
else:
return self.align2localLookup[i]
def global2local(self, gobal_coord, start, end, strand):
"""Returns local coordinate in a global region"""
return global2local(gobal_coord, start, end, strand)
def local2global(self, local_coord, start, end, strand):
"""Return global coordinate within a region from a local coordinate"""
local2global(local_coord, start, end, strand)
def global2align(self, global_coord, start, end, strand):
local_coord = global2local(global_coord, start, end, strand)
# throw exception for out of bounds
if local_coord < 0 or \
local_coord >= len(alignLookup):
raise Exception("coordinate outside [start, end]")
return self.local2alignLookup[local_coord]
def align2global(self, align_coord, start, end, strand):
local_coord = self.align2localLookup[align_coord]
return local2global(local_coord, start, end, strand)
def local2align(seq):
"""
Returns list of indices of non-gap characters
'ATG---CTG-CG' ==> [0,1,2,6,7,8,10,11]
Used to go from local -> align space
"""
lookup = []
for i in xrange(len(seq)):
if seq[i] == "-": continue
lookup.append(i)
return lookup
def align2local(seq):
"""
Returns list such that
'ATG---CTG-CG' ==> [0,1,2,2,2,3,4,5,5,6,7]
Used to go from align -> local space
"""
i = -1
lookup = []
for c in seq:
if c != "-":
i += 1
lookup.append(i)
return lookup
def global2local(gobal_coord, start, end, strand):
"""Returns local coordinate in a global region"""
# swap if strands disagree
if strand == 1:
return gobal_coord - start
else:
return end - gobal_coord
def local2global(local_coord, start, end, strand):
"""Return global coordinate within a region from a local coordinate"""
# swap if strands disagree
if strand == 1:
return local_coord + start
else:
return end - local_coord
def global2align(global_coord, start, end, strand, alignLookup):
local_coord = global2local(global_coord, start, end, strand)
# throw exception for out of bounds
if local_coord < 0 or \
local_coord >= len(alignLookup):
raise Exception("coordinate outside [start, end]")
return alignLookup[local_coord]
def align2global(align_coord, start, end, strand, localLookup):
local_coord = localLookup[align_coord]
return local2global(local_coord, start, end, strand)
#=============================================================================
# old code
'''
def findAlignCodons(aln):
"""find all columns of aligned codons"""
codonAln = mapalign(aln, valfunc=mark_codon_pos)
cols = map(util.hist_dict, zip(* codonAln.values()))
ind = []
codon = []
gaps = defaultdict(lambda: 0)
for i in range(len(cols)):
if len(cols[i]) == 1:
codon.append(i)
elif len(cols[i]) == 2 and -1 in cols[i]:
for key, val in aln.iteritems():
if val[i] == "-":
gaps[key] += 1
codon.append(i)
else:
codon = []
if len(codon) == 3:
if len(gaps) == 0 or \
util.unique([x % 3 for x in gaps.values()]) == [0]:
ind.extend(codon)
codon = []
for key in gaps:
gaps[key] = 0
return ind
def findFourFold(aln):
"""Returns index of all columns in alignment that are completely
fourfold degenerate
"""
aln = filterAlignCodons(aln)
pepAln = mapalign(aln, valfunc=translate)
pep = pepAln.values()[0]
# pep conservation
pepcons = []
for i in xrange(pepAln.alignlen()):
col = [seq[i] for seq in pepAln.itervalues()]
hist = util.hist_dict(col)
if "-" in hist:
del hist["-"]
if "X" in hist:
del hist["X"]
pepcons.append(len(hist) == 1)
ind = []
for i in range(0, len(aln.values()[0]), 3):
if pepcons[i//3]:
degen = AA_DEGEN[pep[i//3]]
for j in range(3):
if degen[j] == 4:
ind.append(i+j)
return ind
'''