<gh_stars>1-10
"""
@author: <NAME>
@contact: <EMAIL>
"""

import click  # type: ignore
from ifpd2.const import CONTEXT_SETTINGS
from ifpd2.dataclasses import Folder, GenomicRegion, FreeEnergyInterval
from ifpd2.dataclasses import NonNegativeInteger, PositiveInteger
from ifpd2.dataclasses import PositiveFloat
from ifpd2.dataclasses import NonNegativeIntInterval
from ifpd2.dataclasses import QueryFocus, QueryWindow
from ifpd2.walker import Walker
from ifpd2.logging import add_log_file_handler
from ifpd2.probe import OligoProbeBuilder
from ifpd2.probe_set import OligoProbeSetBuilder
import logging
from os.path import isdir, isfile, join as path_join
from os import mkdir
from typing import Optional, Tuple


@click.command(
    name="query",
    context_settings=CONTEXT_SETTINGS,
    help="""Design FISH probes on a database chromosome.
    When a --region is not specified, the whole chromosome is used.
    Use -M for the number of probes, and -N for the number of oligos per probe.
    Use -D to specify the minimum distance between consecutive oligos in a probe.

    Use --single to access single-probe design. Same as "-X 1 -w 1", this option
    overrides -X and -w, and ignores -W, if specified.""",
)
@click.argument("db_folder", type=click.Path(exists=True))
@click.argument("chromosome", type=click.STRING)
@click.argument("output_path", metavar="OUTPUT", type=click.Path(exists=False))
@click.option(
    "--region",
    type=click.INT,
    nargs=2,
    default=(0, -1),
    help="Space-separate region start and end location.",
)
@click.option("-M", "--probes", type=click.INT, help="Design M probes.")
@click.option(
    "-N",
    "--oligos",
    type=click.INT,
    default=48,
    help="N oligos per probe. Default: 48",
)
@click.option(
    "-D",
    "--dist",
    type=click.INT,
    default=2,
    help="Consecutive oligo distance. Default: 2",
)
@click.option("--single", is_flag=True, help="Easy access to single probe design.")
@click.option("-W", "--window-size", type=click.INT)
@click.option(
    "-w",
    "--window-shift",
    type=click.FLOAT,
    default=0.1,
    help="Shift as window fraction. Default: 0.1",
)
@click.option(
    "-R",
    "--focus-size",
    type=click.FLOAT,
    default=8e3,
    help="""\b
    Focus size in nt or window fraction.
    Default: 8000""",
)
@click.option(
    "-r",
    "--focus-step",
    type=click.FLOAT,
    default=1e3,
    help="""\b
    Focus step in nt or focus fraction.
    Default: 1000""",
)
@click.option(
    "-F",
    "--off-targets",
    type=click.INT,
    nargs=2,
    default=(0, 99),
    help="""Extremities of acceptable off-target range.
    Default: [0, 99]""",
)
@click.option(
    "-G",
    "--free-energy",
    type=click.FLOAT,
    nargs=2,
    default=(0.0, 0.5),
    help="""Extremities of acceptable 2nd structure dG range,
    in absolute kcal/mol or hybridization dG fraction.
    Default: [0.0, 0.5]""",
)
@click.option(
    "-o",
    "--oligo-score-step",
    type=click.FLOAT,
    default=0.1,
    help="Oligo score relaxation step. Default: 0.1",
)
@click.option(
    "-t",
    "--melting-half-width",
    type=click.FLOAT,
    default=10.0,
    help="Melting range half-width. Default: 10.0",
)
@click.option(
    "-P",
    "--probe-size",
    type=click.INT,
    default=1e4,
    help="Max probe size in nt. Default: 10000",
)
@click.option(
    "-H",
    "--gap-size",
    type=click.FLOAT,
    default=0.1,
    help="""\b
    Max gap size as probe size fraction.
    Default: 0.1""",
)
@click.option(
    "-I",
    "--oligo-intersection",
    type=click.FLOAT,
    default=0.5,
    help="""Probe intersection threshold as shared oligo fraction.
    Default: .5""",
)
@click.option(
    "-k",
    "--oligo-length",
    type=click.INT,
)
@click.option(
    "--threads",
    type=click.INT,
    default=1,
    help="Threads for parallelization. Default: 1",
)
def main(
    db_folder: str,
    chromosome: str,
    output_path: str,
    region: Tuple[int, int],
    probes: Optional[int],
    oligos: int,
    dist: int,
    single: bool,
    window_size: Optional[int],
    window_shift: float,
    focus_size: float,
    focus_step: float,
    off_targets: Tuple[int, int],
    free_energy: Tuple[float, float],
    oligo_score_step: float,
    melting_half_width: float,
    probe_size: int,
    gap_size: float,
    oligo_intersection: float,
    oligo_length: Optional[int],
    threads: int,
) -> None:
    settings = QuerySettings(db_folder, output_path)

    if single:
        probes = 1
        window_shift = 1.0
        window_size = None

    if probes is None and window_size is None:
        raise AssertionError
    if region[1] <= 0:
        probes = None
        logging.info(
            " ".join(
                [
                    "Cannot design a specific number of probes for queries on",
                    "a whole chromosome/feature.",
                ]
            )
        )

    assert_reusable(settings.output_path)

    if not isdir(settings.output_path):
        mkdir(settings.output_path)
    add_log_file_handler(f"{settings.output_path}/ifpd2-main.log")

    opb = OligoProbeBuilder()
    opb.N = PositiveInteger(oligos).n
    opb.D = NonNegativeInteger(dist).n
    opb.Tr = PositiveFloat(melting_half_width).n
    opb.Ps = PositiveInteger(probe_size).n
    opb.Ph = PositiveFloat(gap_size, 1).n
    opb.Po = PositiveFloat(oligo_intersection, 1).n
    opb.k = oligo_length
    opb.F = NonNegativeIntInterval(*off_targets).astuple()
    opb.Gs = FreeEnergyInterval(*free_energy).astuple()
    opb.Ot = PositiveFloat(oligo_score_step, 1).n

    opsb = OligoProbeSetBuilder(path_join(settings.output_path, "probe_sets"))
    logging.info(opb.get_prologue())

    ow = Walker(settings.db_folder_path)
    ow.C = chromosome
    genomic_region = GenomicRegion(*region)
    ow.S = genomic_region.start
    ow.E = max(genomic_region.end, genomic_region.start)
    ow.X = 1 if probes is None else PositiveInteger(probes).n
    window = QueryWindow(window_size, window_shift)
    ow.Ws = window.size
    ow.Wh = window.shift
    focus = QueryFocus(focus_size, focus_step)
    ow.Rs = focus.size
    ow.Rt = focus.step
    ow.out_path = settings.output_path
    ow.reuse = False
    ow.threads = PositiveInteger(threads).n

    ow.start(
        start_from_nt=genomic_region.start,
        end_at_nt=genomic_region.end,
        N=opb.N,
        opb=opb,
        cfr_step=ow.Rt,
    )

    opsb.build(ow.walk_results)
    opsb.export()

    logging.info("Done. :thumbs_up: :smiley:")
    logging.shutdown()


class QuerySettings:
    _db_folder: Folder
    _output_path: Folder

    def __init__(self, db_folder: str, output_path: str):
        super(QuerySettings, self).__init__()
        self._db_folder = Folder(db_folder, True)
        self._output_path = Folder(output_path, False)

    @property
    def db_folder_path(self) -> str:
        return self._db_folder.path

    @property
    def output_path(self) -> str:
        return self._output_path.path

    @property
    def reusable(self) -> bool:
        return False


def assert_reusable(output_path: str):
    assert_msg = " ".join(
        [
            "output path should NOT direct towards an existing directory",
            "or file. Use '--reuse' to load previous results.",
            f"Provided path '{output_path}'",
        ]
    )
    if isfile(output_path):
        raise AssertionError(assert_msg + " leads to a file")
    if isdir(output_path):
        raise AssertionError(assert_msg + " leads to a directory.")

"""
@author: <NAME>
@contact: <EMAIL>
"""

import click  # type: ignore
from ifpd2.const import CONTEXT_SETTINGS
from ifpd2.dataclasses import Folder, GenomicRegion, FreeEnergyInterval
from ifpd2.dataclasses import NonNegativeInteger, PositiveInteger
from ifpd2.dataclasses import PositiveFloat
from ifpd2.dataclasses import NonNegativeIntInterval
from ifpd2.dataclasses import QueryFocus, QueryWindow
from ifpd2.walker import Walker
from ifpd2.logging import add_log_file_handler
from ifpd2.probe import OligoProbeBuilder
from ifpd2.probe_set import OligoProbeSetBuilder
import logging
from os.path import isdir, isfile, join as path_join
from os import mkdir
from typing import Optional, Tuple


@click.command(
    name="query",
    context_settings=CONTEXT_SETTINGS,
    help="""Design FISH probes on a database chromosome.
    When a --region is not specified, the whole chromosome is used.
    Use -M for the number of probes, and -N for the number of oligos per probe.
    Use -D to specify the minimum distance between consecutive oligos in a probe.

    Use --single to access single-probe design. Same as "-X 1 -w 1", this option
    overrides -X and -w, and ignores -W, if specified.""",
)
@click.argument("db_folder", type=click.Path(exists=True))
@click.argument("chromosome", type=click.STRING)
@click.argument("output_path", metavar="OUTPUT", type=click.Path(exists=False))
@click.option(
    "--region",
    type=click.INT,
    nargs=2,
    default=(0, -1),
    help="Space-separate region start and end location.",
)
@click.option("-M", "--probes", type=click.INT, help="Design M probes.")
@click.option(
    "-N",
    "--oligos",
    type=click.INT,
    default=48,
    help="N oligos per probe. Default: 48",
)
@click.option(
    "-D",
    "--dist",
    type=click.INT,
    default=2,
    help="Consecutive oligo distance. Default: 2",
)
@click.option("--single", is_flag=True, help="Easy access to single probe design.")
@click.option("-W", "--window-size", type=click.INT)
@click.option(
    "-w",
    "--window-shift",
    type=click.FLOAT,
    default=0.1,
    help="Shift as window fraction. Default: 0.1",
)
@click.option(
    "-R",
    "--focus-size",
    type=click.FLOAT,
    default=8e3,
    help="""\b
    Focus size in nt or window fraction.
    Default: 8000""",
)
@click.option(
    "-r",
    "--focus-step",
    type=click.FLOAT,
    default=1e3,
    help="""\b
    Focus step in nt or focus fraction.
    Default: 1000""",
)
@click.option(
    "-F",
    "--off-targets",
    type=click.INT,
    nargs=2,
    default=(0, 99),
    help="""Extremities of acceptable off-target range.
    Default: [0, 99]""",
)
@click.option(
    "-G",
    "--free-energy",
    type=click.FLOAT,
    nargs=2,
    default=(0.0, 0.5),
    help="""Extremities of acceptable 2nd structure dG range,
    in absolute kcal/mol or hybridization dG fraction.
    Default: [0.0, 0.5]""",
)
@click.option(
    "-o",
    "--oligo-score-step",
    type=click.FLOAT,
    default=0.1,
    help="Oligo score relaxation step. Default: 0.1",
)
@click.option(
    "-t",
    "--melting-half-width",
    type=click.FLOAT,
    default=10.0,
    help="Melting range half-width. Default: 10.0",
)
@click.option(
    "-P",
    "--probe-size",
    type=click.INT,
    default=1e4,
    help="Max probe size in nt. Default: 10000",
)
@click.option(
    "-H",
    "--gap-size",
    type=click.FLOAT,
    default=0.1,
    help="""\b
    Max gap size as probe size fraction.
    Default: 0.1""",
)
@click.option(
    "-I",
    "--oligo-intersection",
    type=click.FLOAT,
    default=0.5,
    help="""Probe intersection threshold as shared oligo fraction.
    Default: .5""",
)
@click.option(
    "-k",
    "--oligo-length",
    type=click.INT,
)
@click.option(
    "--threads",
    type=click.INT,
    default=1,
    help="Threads for parallelization. Default: 1",
)
def main(
    db_folder: str,
    chromosome: str,
    output_path: str,
    region: Tuple[int, int],
    probes: Optional[int],
    oligos: int,
    dist: int,
    single: bool,
    window_size: Optional[int],
    window_shift: float,
    focus_size: float,
    focus_step: float,
    off_targets: Tuple[int, int],
    free_energy: Tuple[float, float],
    oligo_score_step: float,
    melting_half_width: float,
    probe_size: int,
    gap_size: float,
    oligo_intersection: float,
    oligo_length: Optional[int],
    threads: int,
) -> None:
    settings = QuerySettings(db_folder, output_path)

    if single:
        probes = 1
        window_shift = 1.0
        window_size = None

    if probes is None and window_size is None:
        raise AssertionError
    if region[1] <= 0:
        probes = None
        logging.info(
            " ".join(
                [
                    "Cannot design a specific number of probes for queries on",
                    "a whole chromosome/feature.",
                ]
            )
        )

    assert_reusable(settings.output_path)

    if not isdir(settings.output_path):
        mkdir(settings.output_path)
    add_log_file_handler(f"{settings.output_path}/ifpd2-main.log")

    opb = OligoProbeBuilder()
    opb.N = PositiveInteger(oligos).n
    opb.D = NonNegativeInteger(dist).n
    opb.Tr = PositiveFloat(melting_half_width).n
    opb.Ps = PositiveInteger(probe_size).n
    opb.Ph = PositiveFloat(gap_size, 1).n
    opb.Po = PositiveFloat(oligo_intersection, 1).n
    opb.k = oligo_length
    opb.F = NonNegativeIntInterval(*off_targets).astuple()
    opb.Gs = FreeEnergyInterval(*free_energy).astuple()
    opb.Ot = PositiveFloat(oligo_score_step, 1).n

    opsb = OligoProbeSetBuilder(path_join(settings.output_path, "probe_sets"))
    logging.info(opb.get_prologue())

    ow = Walker(settings.db_folder_path)
    ow.C = chromosome
    genomic_region = GenomicRegion(*region)
    ow.S = genomic_region.start
    ow.E = max(genomic_region.end, genomic_region.start)
    ow.X = 1 if probes is None else PositiveInteger(probes).n
    window = QueryWindow(window_size, window_shift)
    ow.Ws = window.size
    ow.Wh = window.shift
    focus = QueryFocus(focus_size, focus_step)
    ow.Rs = focus.size
    ow.Rt = focus.step
    ow.out_path = settings.output_path
    ow.reuse = False
    ow.threads = PositiveInteger(threads).n

    ow.start(
        start_from_nt=genomic_region.start,
        end_at_nt=genomic_region.end,
        N=opb.N,
        opb=opb,
        cfr_step=ow.Rt,
    )

    opsb.build(ow.walk_results)
    opsb.export()

    logging.info("Done. :thumbs_up: :smiley:")
    logging.shutdown()


class QuerySettings:
    _db_folder: Folder
    _output_path: Folder

    def __init__(self, db_folder: str, output_path: str):
        super(QuerySettings, self).__init__()
        self._db_folder = Folder(db_folder, True)
        self._output_path = Folder(output_path, False)

    @property
    def db_folder_path(self) -> str:
        return self._db_folder.path

    @property
    def output_path(self) -> str:
        return self._output_path.path

    @property
    def reusable(self) -> bool:
        return False


def assert_reusable(output_path: str):
    assert_msg = " ".join(
        [
            "output path should NOT direct towards an existing directory",
            "or file. Use '--reuse' to load previous results.",
            f"Provided path '{output_path}'",
        ]
    )
    if isfile(output_path):
        raise AssertionError(assert_msg + " leads to a file")
    if isdir(output_path):
        raise AssertionError(assert_msg + " leads to a directory.")
@author: <NAME> @contact: <EMAIL> # type: ignore Design FISH probes on a database chromosome.     When a --region is not specified, the whole chromosome is used.     Use -M for the number of probes, and -N for the number of oligos per probe.     Use -D to specify the minimum distance between consecutive oligos in a probe.      Use --single to access single-probe design. Same as "-X 1 -w 1", this option     overrides -X and -w, and ignores -W, if specified. \b     Focus size in nt or window fraction.     Default: 8000 \b     Focus step in nt or focus fraction.     Default: 1000 Extremities of acceptable off-target range.     Default: [0, 99] Extremities of acceptable 2nd structure dG range,     in absolute kcal/mol or hybridization dG fraction.     Default: [0.0, 0.5] \b     Max gap size as probe size fraction.     Default: 0.1 Probe intersection threshold as shared oligo fraction.     Default: .5