def is_fusion_compatible(r1, r2, max_fusion_point_dist, allow_extra_5_exons):
"""
Helper function for: merge_fusion_exons()
Check that:
(1) r1, r2 and both in the 5', or both in the 3'
(2) if single-exon, fusion point must be close by
if multi-exon, every junction identical (plus below is True)
(3) if allow_extra_5_exons is False, num exons must be the same
if allow_extra_5_exons is True, only allow additional 5' exons
"""
MAX_QSTART_FOR_5 = 100
# first need to figure out ends
# also check that both are in the 5' portion of r1 and r2
assert r1.flag.strand == r2.flag.strand
if r1.qStart < MAX_QSTART_FOR_5: # in the 5' portion of r1
if r2.qStart > MAX_QSTART_FOR_5: # in the 3' portion, reject
return False
in_5_portion = True
else: # in the 3' portion of r1
if r2.qStart < MAX_QSTART_FOR_5:
return False
in_5_portion = False
plus_is_5end = (r1.flag.strand == '+')
type = compare_junctions.compare_junctions(r1, r2)
if type == 'exact':
if len(r1.segments) == 1:
if len(r2.segments) == 1:
# single exon case, check fusion point is close enough
if in_5_portion and plus_is_5end:
dist = abs(r1.sStart - r2.sStart)
else:
dist = abs(r1.sEnd - r2.sEnd)
return dist <= max_fusion_point_dist
else:
raise Exception, "Not possible case for multi-exon transcript and " + \
"single-exon transcript to be exact!"
else: # multi-exon case, must be OK
return True
elif type == 'super' or type == 'subset':
if allow_extra_5_exons:
# check that the 3' junction is identical
# also check that the 3' end is relatively close
if in_5_portion and plus_is_5end:
if r1.segments[-1].start != r2.segments[-1].start: return False
if abs(r1.segments[-1].end -
r2.segments[-1].end) > max_fusion_point_dist:
return False
elif in_5_portion and (not plus_is_5end):
if r1.segments[0].end != r2.segments[0].end: return False
if abs(r1.segments[0].start -
r2.segments[0].start) > max_fusion_point_dist:
return False
else:
return False
else: # not OK because number of exons must be the same
return False
else: #ex: partial, nomatch, etc...
return False
def is_fusion_compatible(r1, r2, max_fusion_point_dist, max_exon_end_dist, allow_extra_5_exons):
"""
Helper function for: merge_fusion_exons()
Check that:
(1) r1, r2 and both in the 5', or both in the 3'
(2) if single-exon, fusion point must be close by
if multi-exon, every junction identical (plus below is True)
(3) if allow_extra_5_exons is False, num exons must be the same
if allow_extra_5_exons is True, only allow additional 5' exons
"""
# _ids = 'i1a_c1603/f67p459/1248,i1b_c19881/f7p368/1235,newClontech_i0HQ|c18279/f6p24/1229,i2b_c22046/f2p494/2157,i2a_c4714/f10p554/2152'.split(',')
# if r1.qID in _ids or r2.qID in _ids:
# pdb.set_trace()
# first need to figure out ends
# also check that both are in the 5' portion of r1 and r2
assert r1.flag.strand == r2.flag.strand
if r1.qStart <= .5*r1.qLen: # in the 5' portion of r1
if r2.qStart > .5*r2.qLen: # in the 3' portion, reject
return False
in_5_portion = True
else: # in the 3' portion of r1
if r2.qStart <= .5*r2.qLen:
return False
in_5_portion = False
plus_is_5end = (r1.flag.strand == '+')
type = compare_junctions.compare_junctions(r1, r2)
if type == 'exact':
if len(r1.segments) == 1:
if len(r2.segments) == 1:
# single exon case, check fusion point is close enough
if in_5_portion and plus_is_5end: dist = abs(r1.sStart - r2.sStart)
else: dist = abs(r1.sEnd - r2.sEnd)
return dist <= max_fusion_point_dist
else:
raise Exception, "Not possible case for multi-exon transcript and " + \
"single-exon transcript to be exact!"
else: # multi-exon case, must be OK
return True
elif type == 'super' or type == 'subset':
if allow_extra_5_exons:
# check that the 3' junction is identical
# also check that the 3' end is relatively close
if in_5_portion and plus_is_5end:
if abs(r1.segments[-1].start - r2.segments[-1].start) > max_exon_end_dist: return False
if abs(r1.segments[-1].end - r2.segments[-1].end) > max_fusion_point_dist: return False
return True
elif in_5_portion and (not plus_is_5end):
if abs(r1.segments[0].end - r2.segments[0].end) > max_exon_end_dist: return False
if abs(r1.segments[0].start - r2.segments[0].start) > max_fusion_point_dist: return False
return True
else:
return False
else: # not OK because number of exons must be the same
return False
else: #ex: partial, nomatch, etc...
return False
def match_record_to_tree(self, r):
"""
r --- GMAPRecord
tree --- dict of chromosome --> strand --> IntervalTree
If exact match (every exon junction), return the matching GMAPRecord
Otherwise return None
*NOTE*: the tree should be non-redundant so can return as soon as exact match is found!
"""
matches = self.tree[r.chr][r.strand].find(r.start, r.end)
for r2 in matches:
r.segments = r.ref_exons
r2.segments = r2.ref_exons
if compare_junctions.compare_junctions(r, r2, internal_fuzzy_max_dist=self.internal_fuzzy_max_dist) == 'exact': # is a match!
return r2
return None
def match_record_to_tree(self, r):
"""
r --- GMAPRecord
tree --- dict of chromosome --> strand --> IntervalTree
If exact match (every exon junction), return the matching GMAPRecord
Otherwise return None
*NOTE*: the tree should be non-redundant so can return as soon as exact match is found!
"""
matches = self.tree[r.chr][r.strand].find(r.start, r.end)
for r2 in matches:
r.segments = r.ref_exons
r2.segments = r2.ref_exons
if compare_junctions.compare_junctions(
r, r2, internal_fuzzy_max_dist=self.internal_fuzzy_max_dist
) == 'exact': # is a match!
return r2
return None
def filter_out_subsets(recs, internal_fuzzy_max_dist):
# recs must be sorted by start becuz that's the order they are written
i = 0
while i < len(recs)-1:
j = i + 1
while j < len(recs):
if recs[j].start > recs[i].end:
break
recs[i].segments = recs[i].ref_exons
recs[j].segments = recs[j].ref_exons
m = compare_junctions.compare_junctions(recs[i], recs[j], internal_fuzzy_max_dist)
if can_merge(m, recs[i], recs[j], internal_fuzzy_max_dist):
if m == 'super': # pop recs[j]
recs.pop(j)
else:
recs.pop(i)
j += 1
else:
j += 1
i += 1
def is_fusion_compatible(r1, r2, max_fusion_point_dist, max_exon_end_dist,
allow_extra_5_exons):
"""
Helper function for: merge_fusion_exons()
Check that:
(1) r1, r2 and both in the 5', or both in the 3'
(2) if single-exon, fusion point must be close by
if multi-exon, every junction identical (plus below is True)
(3) if allow_extra_5_exons is False, num exons must be the same
if allow_extra_5_exons is True, only allow additional 5' exons
"""
# _ids = 'i1a_c1603/f67p459/1248,i1b_c19881/f7p368/1235,newClontech_i0HQ|c18279/f6p24/1229,i2b_c22046/f2p494/2157,i2a_c4714/f10p554/2152'.split(',')
# if r1.qID in _ids or r2.qID in _ids:
# pdb.set_trace()
# first need to figure out ends
# also check that both are in the 5' portion of r1 and r2
assert r1.flag.strand == r2.flag.strand
if r1.qStart <= .5 * r1.qLen: # in the 5' portion of r1
if r2.qStart > .5 * r2.qLen: # in the 3' portion, reject
return False
in_5_portion = True
else: # in the 3' portion of r1
if r2.qStart <= .5 * r2.qLen:
return False
in_5_portion = False
plus_is_5end = (r1.flag.strand == '+')
type = compare_junctions.compare_junctions(r1, r2)
if type == 'exact':
if len(r1.segments) == 1:
if len(r2.segments) == 1:
# single exon case, check fusion point is close enough
if in_5_portion and plus_is_5end:
dist = abs(r1.sStart - r2.sStart)
else:
dist = abs(r1.sEnd - r2.sEnd)
return dist <= max_fusion_point_dist
else:
raise Exception, "Not possible case for multi-exon transcript and " + \
"single-exon transcript to be exact!"
else: # multi-exon case, must be OK
return True
elif type == 'super' or type == 'subset':
if allow_extra_5_exons:
# check that the 3' junction is identical
# also check that the 3' end is relatively close
if in_5_portion and plus_is_5end:
if abs(r1.segments[-1].start -
r2.segments[-1].start) > max_exon_end_dist:
return False
if abs(r1.segments[-1].end -
r2.segments[-1].end) > max_fusion_point_dist:
return False
return True
elif in_5_portion and (not plus_is_5end):
if abs(r1.segments[0].end -
r2.segments[0].end) > max_exon_end_dist:
return False
if abs(r1.segments[0].start -
r2.segments[0].start) > max_fusion_point_dist:
return False
return True
else:
return False
else: # not OK because number of exons must be the same
return False
else: #ex: partial, nomatch, etc...
return False
def collapse_fuzzy_junctions(gff_filename, group_filename, allow_extra_5exon,
internal_fuzzy_max_dist):
def get_fl_from_id(members):
# ex: 13cycle_1Mag1Diff|i0HQ_SIRV_1d1m|c139597/f1p0/178
return sum(int(_id.split('/')[1].split('p')[0][1:]) for _id in members)
def can_merge(m, r1, r2):
if m == 'exact':
return True
else:
if not allow_extra_5exon:
return False
# below is continued only if (a) is 'subset' or 'super' AND (b) allow_extra_5exon is True
if m == 'subset':
r1, r2 = r2, r1 # rotate so r1 is always the longer one
if m == 'super' or m == 'subset':
n2 = len(r2.ref_exons)
# check that (a) r1 and r2 end on same 3' exon, that is the last acceptor site agrees
# AND (b) the 5' start of r2 is sandwiched between the matching r1 exon coordinates
if r1.strand == '+':
return abs(r1.ref_exons[-1].start - r2.ref_exons[-1].start) <= internal_fuzzy_max_dist and \
r1.ref_exons[-n2].start <= r2.ref_exons[0].start < r1.ref_exons[-n2].end
else:
return abs(r1.ref_exons[0].end - r2.ref_exons[0].end) <= internal_fuzzy_max_dist and \
r1.ref_exons[n2-1].start <= r2.ref_exons[-1].end < r1.ref_exons[n2].end
return False
d = {}
recs = defaultdict(lambda: {
'+': IntervalTree(),
'-': IntervalTree()
}) # chr --> strand --> tree
fuzzy_match = defaultdict(lambda: [])
for r in GFF.collapseGFFReader(gff_filename):
d[r.seqid] = r
has_match = False
r.segments = r.ref_exons
for r2 in recs[r.chr][r.strand].find(r.start, r.end):
r2.segments = r2.ref_exons
m = compare_junctions.compare_junctions(
r, r2, internal_fuzzy_max_dist=internal_fuzzy_max_dist)
if can_merge(m, r, r2):
fuzzy_match[r2.seqid].append(r.seqid)
has_match = True
break
if not has_match:
recs[r.chr][r.strand].insert(r.start, r.end, r)
fuzzy_match[r.seqid] = [r.seqid]
group_info = {}
with open(group_filename) as f:
for line in f:
pbid, members = line.strip().split('\t')
group_info[pbid] = [x for x in members.split(',')]
# pick for each fuzzy group the one that has the most exons (if tie, then most FL)
keys = fuzzy_match.keys()
keys.sort(key=lambda x: map(int, x.split('.')[1:]))
f_gff = open(gff_filename + '.fuzzy', 'w')
f_group = open(group_filename + '.fuzzy', 'w')
for k in keys:
all_members = []
best_pbid, best_size, best_num_exons = fuzzy_match[k][0], len(
group_info[fuzzy_match[k][0]]), len(d[fuzzy_match[k][0]].ref_exons)
all_members += group_info[fuzzy_match[k][0]]
for pbid in fuzzy_match[k][1:]:
_size = get_fl_from_id(group_info[pbid])
_num_exons = len(d[pbid].ref_exons)
all_members += group_info[pbid]
if _num_exons > best_num_exons or (_num_exons == best_num_exons
and _size > best_size):
best_pbid, best_size, best_num_exons = pbid, _size, _num_exons
GFF.write_collapseGFF_format(f_gff, d[best_pbid])
f_group.write("{0}\t{1}\n".format(best_pbid, ",".join(all_members)))
f_gff.close()
f_group.close()
return fuzzy_match
def collapse_fuzzy_junctions(gff_filename, group_filename, allow_extra_5exon, internal_fuzzy_max_dist):
def get_fl_from_id(members):
# ex: 13cycle_1Mag1Diff|i0HQ_SIRV_1d1m|c139597/f1p0/178
return sum(int(_id.split('/')[1].split('p')[0][1:]) for _id in members)
def can_merge(m, r1, r2):
if m == 'exact':
return True
else:
if not allow_extra_5exon:
return False
# below is continued only if (a) is 'subset' or 'super' AND (b) allow_extra_5exon is True
if m == 'subset':
r1, r2 = r2, r1 # rotate so r1 is always the longer one
if m == 'super' or m == 'subset':
n2 = len(r2.ref_exons)
# check that (a) r1 and r2 end on same 3' exon, that is the last acceptor site agrees
# AND (b) the 5' start of r2 is sandwiched between the matching r1 exon coordinates
if r1.strand == '+':
return abs(r1.ref_exons[-1].start - r2.ref_exons[-1].start) <= internal_fuzzy_max_dist and \
r1.ref_exons[-n2].start <= r2.ref_exons[0].start < r1.ref_exons[-n2].end
else:
return abs(r1.ref_exons[0].end - r2.ref_exons[0].end) <= internal_fuzzy_max_dist and \
r1.ref_exons[n2-1].start <= r2.ref_exons[-1].end < r1.ref_exons[n2].end
return False
d = {}
recs = defaultdict(lambda: {'+':IntervalTree(), '-':IntervalTree()}) # chr --> strand --> tree
fuzzy_match = defaultdict(lambda: [])
for r in GFF.collapseGFFReader(gff_filename):
d[r.seqid] = r
has_match = False
r.segments = r.ref_exons
for r2 in recs[r.chr][r.strand].find(r.start, r.end):
r2.segments = r2.ref_exons
m = compare_junctions.compare_junctions(r, r2, internal_fuzzy_max_dist=internal_fuzzy_max_dist)
if can_merge(m, r, r2):
fuzzy_match[r2.seqid].append(r.seqid)
has_match = True
break
if not has_match:
recs[r.chr][r.strand].insert(r.start, r.end, r)
fuzzy_match[r.seqid] = [r.seqid]
group_info = {}
with open(group_filename) as f:
for line in f:
pbid, members = line.strip().split('\t')
group_info[pbid] = [x for x in members.split(',')]
# pick for each fuzzy group the one that has the most exons (if tie, then most FL)
keys = fuzzy_match.keys()
keys.sort(key=lambda x: map(int, x.split('.')[1:]))
f_gff = open(gff_filename+'.fuzzy', 'w')
f_group = open(group_filename+'.fuzzy', 'w')
for k in keys:
all_members = []
best_pbid, best_size, best_num_exons = fuzzy_match[k][0], len(group_info[fuzzy_match[k][0]]), len(d[fuzzy_match[k][0]].ref_exons)
all_members += group_info[fuzzy_match[k][0]]
for pbid in fuzzy_match[k][1:]:
_size = get_fl_from_id(group_info[pbid])
_num_exons = len(d[pbid].ref_exons)
all_members += group_info[pbid]
if _num_exons > best_num_exons or (_num_exons == best_num_exons and _size > best_size):
best_pbid, best_size, best_num_exons = pbid, _size, _num_exons
GFF.write_collapseGFF_format(f_gff, d[best_pbid])
f_group.write("{0}\t{1}\n".format(best_pbid, ",".join(all_members)))
f_gff.close()
f_group.close()
return fuzzy_match