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#!/usr/bin/python3
"""Map features from the target species to the query species of a chain alignment file.
This is intended for mapping relatively short features such as Chip-Seq
peaks on TF binding events. Features that when mapped
span multiple chains or multiple chromosomes are silently filtered out. TODO:
(1)for narrowPeak input, map the predicted peak position.
"""
import argparse
import logging
import os
import sys
from functools import reduce
from itertools import groupby
from operator import (
attrgetter,
itemgetter,
)
import numpy as np
from bx.align import epo
from bx.align.epo import bed_union as elem_u
from bx.intervals.intersection import (
Interval,
IntervalTree,
)
elem_t = np.dtype([("chrom", np.str_, 30), ("start", np.int64), ("end", np.int64), ("id", np.str_, 100)])
narrowPeak_t = np.dtype(
[
("chrom", np.str_, 30),
("start", np.int64),
("end", np.int64),
("id", np.str_, 100),
("score", np.int64),
("strand", np.str_, 1),
("signalValue", float),
("pValue", float),
("qValue", float),
("peak", np.int64),
]
)
LOG_LEVELS = {"info": logging.INFO, "debug": logging.DEBUG, "silent": logging.ERROR}
logging.basicConfig()
log = logging.getLogger()
class GIntervalTree(IntervalTree):
"""a set of IntervalTrees that is indexed by chromosomes"""
def __init__(self):
self._trees = {}
def add(self, chrom, element):
"""insert an element. use this method as the IntervalTree one.
this will simply call the IntervalTree.add method on the right tree
:param chrom: chromosome
:param element: the argument of IntervalTree.insert_interval
:return: None
"""
self._trees.setdefault(chrom, IntervalTree()).insert_interval(element)
def find(self, chrom, start, end):
"""find the intersecting elements
:param chrom: chromosome
:param start: start
:param end: end
:return: a list of intersecting elements"""
tree = self._trees.get(chrom, None)
if tree:
return tree.find(start, end)
# return always a list
return []
def transform(elem, chain_CT_CQ, max_gap):
"""transform the coordinates of this elem into the other species.
elem intersects this chain's ginterval.
:return: a list of the type [(to_chr, start, end, elem[id]) ... ]"""
(chain, CT, CQ) = chain_CT_CQ
start, end = max(elem["start"], chain.tStart) - chain.tStart, min(elem["end"], chain.tEnd) - chain.tStart
assert np.all((CT[:, 1] - CT[:, 0]) == (CQ[:, 1] - CQ[:, 0]))
to_chrom = chain.qName
to_gab_start = chain.qStart
start_idx = np.where(CT[:, 1] > start)[0][0]
end_idx = np.where(CT[:, 0] < end)[0][-1]
if start_idx > end_idx: # maps to a gap region on the other species
return []
# apply the gap threshold
if max_gap >= 0 and start_idx < end_idx - 1:
if (
np.max(CT[(start_idx + 1) : end_idx, 0] - CT[start_idx : (end_idx - 1), 1]) > max_gap
or np.max(CQ[(start_idx + 1) : end_idx, 0] - CQ[start_idx : (end_idx - 1), 1]) > max_gap
):
return []
assert start < CT[start_idx, 1]
assert CT[end_idx, 0] < end
to_start = CQ[start_idx, 0] + max(0, start - CT[start_idx, 0]) # correct if on middle of interval
to_end = CQ[end_idx, 1] - max(0, CT[end_idx, 1] - end) # idem
if start_idx == end_idx: # elem falls in a single run of matches
slices = [(to_start, to_end)]
else:
slices = [(to_start, CQ[start_idx, 1])]
slices += [(CQ[i, 0], CQ[i, 1]) for i in range(start_idx + 1, end_idx)]
slices.append((CQ[end_idx, 0], to_end))
if chain.qStrand == "-":
Sz = chain.qEnd - chain.qStart
slices = [(Sz - t[1], Sz - t[0]) for t in slices]
return [(to_chrom, to_gab_start + t[0], to_gab_start + t[1], elem["id"]) for t in slices]
def union_elements(elements):
"""elements = [(chr, s, e, id), ...], this is to join elements that have a
deletion in the 'to' species
"""
if len(elements) < 2:
return elements
assert {e[3] for e in elements} == {elements[0][3]}, "more than one id"
el_id = elements[0][3]
unioned_elements = []
for ch, chgrp in groupby(elements, key=itemgetter(0)):
for s, e in elem_u(np.array([itemgetter(1, 2)(_) for _ in chgrp], dtype=np.uint)):
if s < e:
unioned_elements.append((ch, s, e, el_id))
assert len(unioned_elements) <= len(elements)
return unioned_elements
def transform_by_chrom(all_epo, from_elem_list, tree, chrom, opt, out_fd):
BED4_FRM = "%s\t%d\t%d\t%s\n"
BED12_FRM = "%s\t%d\t%d\t%s\t1000\t+\t%d\t%d\t0,0,0\t%d\t%s\t%s\n"
NPEAK_FRM = "%s\t%d\t%d\t%s\t%d\t%s\t%f\t%f\t%f\t%d\n"
assert len(set(from_elem_list["chrom"])) <= 1
mapped_elem_count = 0
mapped_summit_count = 0
for from_elem in from_elem_list:
matching_block_ids = [attrgetter("value")(_) for _ in tree.find(chrom, from_elem["start"], from_elem["end"])]
# do the actual mapping
to_elem_slices = [_ for _ in (transform(from_elem, all_epo[i], opt.gap) for i in matching_block_ids) if _]
""" # Original version: silently discard split alignments
if len(to_elem_slices) > 1 or len(to_elem_slices) == 0:
log.debug("%s no match or in different chain/chromosomes" % (str(from_elem)))
continue
to_elem_slices = to_elem_slices[0]
"""
""" Modified version below allows liftOver-like behavior of
keeping the longest alignment when alignments are split across
multiple chains. Added by Adam Diehl (adadiehl@umich.edu)
"""
max_elem_idx = 0
if len(to_elem_slices) == 0:
log.debug("%s: no match in target: discarding.", from_elem)
continue
elif len(to_elem_slices) > 1 and opt.keep_split:
log.debug("%s spans multiple chains/chromosomes. Using longest alignment.", from_elem)
max_elem_len = 0
for i in range(len(to_elem_slices)):
elem_len = to_elem_slices[i][-1][2] - to_elem_slices[i][0][2]
if elem_len > max_elem_len:
max_elem_len = elem_len
max_elem_idx = i
elif len(to_elem_slices) > 1:
log.debug("%s spans multiple chains/chromosomes: discarding.", from_elem)
continue
to_elem_slices = to_elem_slices[max_elem_idx]
""" End AGD modifications """
# apply threshold
if (from_elem[2] - from_elem[1]) * opt.threshold > reduce(lambda b, a: a[2] - a[1] + b, to_elem_slices, 0):
log.debug("%s did not pass threshold", from_elem)
continue
# if to_species had insertions you can join elements
to_elem_list = sorted(union_elements(to_elem_slices), key=lambda a: a[1])
if to_elem_list:
mapped_elem_count += 1
log.debug("\tjoined to %d elements", len(to_elem_list))
start = to_elem_list[0][1]
end = to_elem_list[-1][2]
if opt.format == "BED4":
for tel in to_elem_list:
out_fd.write(BED4_FRM % tel)
elif opt.format == "BED12":
out_fd.write(
BED12_FRM
% (
to_elem_list[0][0],
start,
end,
from_elem["id"],
start,
end,
len(to_elem_list),
",".join("%d" % (e[2] - e[1]) for e in to_elem_list),
",".join("%d" % (e[1] - start) for e in to_elem_list),
)
)
else:
# narrowPeak convention is to report the peak location relative to start
peak = int((start + end) / 2) - start
if opt.in_format == "narrowPeak":
# Map the peak location
# sys.stderr.write("{}\n".format(from_elem))
matching_block_ids = [
attrgetter("value")(_) for _ in tree.find(chrom, from_elem["peak"], from_elem["peak"])
]
p_elem_slices = [
_
for _ in (
transform(
np.array((chrom, from_elem["peak"], from_elem["peak"], "."), dtype=elem_t),
all_epo[i],
opt.gap,
)
for i in matching_block_ids
)
if _
]
if len(p_elem_slices) >= 1:
mapped_summit_count += 1
sys.stderr.write(f"{p_elem_slices}\n")
# Make sure the peak is between the start and end positions
if p_elem_slices[0][0][1] >= start and p_elem_slices[0][0][1] <= end:
peak = p_elem_slices[0][0][1] - start
else:
mapped_summit_count -= 1
log.debug(
"Warning: elem %s summit mapped location falls outside the mapped element start and end. Using the mapped elem midpoint instead.",
from_elem,
)
else:
log.debug(
"Warning: elem %s summit maps to a gap region in the target alignment. Using the mapped elem midpoint instead.",
from_elem,
)
out_fd.write(
NPEAK_FRM
% (
to_elem_list[0][0],
start,
end,
from_elem["id"],
from_elem["score"],
from_elem["strand"],
from_elem["signalValue"],
from_elem["pValue"],
from_elem["qValue"],
peak,
)
)
log.info("%s: %d of %d elements mapped", chrom, mapped_elem_count, from_elem_list.shape[0])
if opt.format == "narrowPeak" and opt.in_format == "narrowPeak":
log.info("%s: %d peak summits from %d mapped elements mapped", chrom, mapped_summit_count, mapped_elem_count)
def transform_file(ELEMS, ofname, EPO, TREE, opt):
"transform/map the elements of this file and dump the output on 'ofname'"
BED4_FRM = "%s\t%d\t%d\t%s\n"
log.info("%s (%d) elements ...", opt.screen and "screening" or "transforming", ELEMS.shape[0])
with open(ofname, "w") as out_fd:
if opt.screen:
for elem in ELEMS.flat:
matching_blocks = [attrgetter("value")(_) for _ in TREE.find(elem["chrom"], elem["start"], elem["end"])]
assert set(matching_blocks) <= set(EPO.keys())
if matching_blocks:
out_fd.write(BED4_FRM % elem)
else:
for chrom in set(ELEMS["chrom"]):
transform_by_chrom(EPO, ELEMS[ELEMS["chrom"] == chrom], TREE, chrom, opt, out_fd)
log.info("DONE!")
def loadChains(path):
"name says it."
EPO = epo.Chain._parse_file(path, True)
# convert coordinates w.r.t the forward strand (into slices)
# compute cumulative intervals
for i in range(len(EPO)):
ch, S, T, Q = EPO[i]
if ch.tStrand == "-":
ch = ch._replace(tEnd=ch.tSize - ch.tStart, tStart=ch.tSize - ch.tEnd)
if ch.qStrand == "-":
ch = ch._replace(qEnd=ch.qSize - ch.qStart, qStart=ch.qSize - ch.qEnd)
EPO[i] = (ch, epo.cumulative_intervals(S, T), epo.cumulative_intervals(S, Q))
# now each element of epo is (chain_header, target_intervals, query_intervals)
assert all(t[0].tStrand == "+" for t in EPO), "all target strands should be +"
return EPO
def loadFeatures(path, opt):
"""
Load features. For BED, only BED4 columns are loaded.
For narrowPeak, all columns are loaded.
"""
log.info("loading from %s ...", path)
data = []
if opt.in_format == "BED":
with open(path) as fd:
for line in fd:
cols = line.split()
data.append((cols[0], int(cols[1]), int(cols[2]), cols[3]))
data = np.array(data, dtype=elem_t)
else:
with open(path) as fd:
for line in fd:
cols = line.split()
data.append(
(
cols[0],
int(cols[1]),
int(cols[2]),
cols[3],
int(cols[4]),
cols[5],
float(cols[6]),
float(cols[7]),
float(cols[8]),
int(cols[-1]) + int(cols[1]),
)
)
data = np.array(data, dtype=narrowPeak_t)
return data
if __name__ == "__main__":
parser = argparse.ArgumentParser(
description=__doc__, epilog="Olgert Denas (Taylor Lab)", formatter_class=argparse.ArgumentDefaultsHelpFormatter
)
parser.add_argument(
"input",
nargs="+",
help="Input to process. If more than a file is specified, all files will be mapped and placed on --output, which should be a directory.",
)
parser.add_argument("alignment", help="Alignment file (.chain or .pkl)")
parser.add_argument(
"-f",
"--format",
choices=("BED4", "BED12", "narrowPeak"),
default="BED4",
help="Output format. BED4 output reports all aligned blocks as separate BED records. BED12 reports a single BED record for each mapped element, with individual blocks given in the BED12 fields. NarrowPeak reports a single narrowPeak record for each mapped element, in which the chromosome, start, end, and peak positions are mapped to the target species and all other columns are passed through unchanged.",
)
parser.add_argument(
"-o",
"--output",
metavar="FILE",
default="stdout",
type=lambda s: ((s in ("stdout", "-") and "/dev/stdout") or s),
help="Output file. Mandatory if more than on file in input.",
)
parser.add_argument(
"-t",
"--threshold",
metavar="FLOAT",
default=0.0,
type=float,
help="Mapping threshold i.e., |elem| * threshold <= |mapped_elem|",
)
parser.add_argument(
"-s",
"--screen",
default=False,
action="store_true",
help="Only report elements in the alignment (without mapping). -t has not effect here (TODO)",
)
parser.add_argument(
"-g", "--gap", type=int, default=-1, help="Ignore elements with an insertion/deletion of this or bigger size."
)
parser.add_argument(
"-v", "--verbose", type=str, choices=list(LOG_LEVELS.keys()), default="info", help="Verbosity level"
)
parser.add_argument(
"-k",
"--keep_split",
default=False,
action="store_true",
help="If elements span multiple chains, report the segment with the longest overlap instead of silently dropping them. (This is the default behavior for liftOver.)",
)
parser.add_argument("-i", "--in_format", choices=["BED", "narrowPeak"], default="BED", help="Input file format.")
opt = parser.parse_args()
log.setLevel(LOG_LEVELS[opt.verbose])
# check for output if input is a directory arguments
if len(opt.input) > 1 and (not os.path.isdir(opt.output)):
parser.error("For multiple inputs, output is mandatory and should be a dir.")
# loading alignments from opt.alignment
EPO = {ch[0].id: ch for ch in loadChains(opt.alignment)}
# create an interval tree based on chain headers (from_species side)
# for fast feature-to-chain_header searching
log.info("indexing %d chains ...", len(EPO))
TREE = GIntervalTree()
for gabid in EPO:
chain, t, q = EPO[gabid]
TREE.add(chain.tName, Interval(chain.tStart, chain.tEnd, chain.id))
# transform elements
if len(opt.input) > 1:
for inpath in opt.input:
if not os.path.isfile(inpath):
log.warning("skipping %s (not a file) ...", inpath)
continue
outpath = os.path.join(opt.output, os.path.basename(inpath))
if os.path.isfile(outpath):
log.warning("overwriting %s ...", outpath)
transform_file(loadFeatures(inpath), outpath, EPO, TREE, opt)
else:
transform_file(loadFeatures(opt.input[0], opt), opt.output, EPO, TREE, opt)
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