#!/opt/mambaforge/envs/bioconda/conda-bld/bx-python_1753187629420/_h_env_placehold_placehold_placehold_placehold_placehold_placehold_placehold_placehold_placehold_placehold_placehold_placehold_placehold_placehold_placehold_placehold_placehold_placehold_plac/bin/python

"""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 cummulative 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.cummulative_intervals(S, T), epo.cummulative_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)
