diff --git a/.gitignore b/.gitignore index 3db890198..d2c7af591 100644 --- a/.gitignore +++ b/.gitignore @@ -43,6 +43,7 @@ __pycache__ .pypirc .gitignore +.python-version chauthorinfo.sh pre-commit.sh @@ -55,3 +56,5 @@ Documentation/* *log *BAK *.sublime* +*.code-workspace +.vscode/ diff --git a/Dockerfile b/Dockerfile new file mode 100644 index 000000000..a7484d773 --- /dev/null +++ b/Dockerfile @@ -0,0 +1,19 @@ +FROM python:3.10.5-slim-buster + +WORKDIR /app + +COPY ./scripts/motif_search/ . + +COPY ./prody ./prody + +RUN apt update -y && \ + apt install build-essential -y + +RUN pip install --upgrade pip setuptools wheel + +RUN pip install -r requirements.txt + +RUN rm requirements.txt + +CMD ["flask", "run", "--host", "0.0.0.0", "--port", "5000"] + diff --git a/prody/database/__init__.py b/prody/database/__init__.py index 4091df195..5178ec852 100644 --- a/prody/database/__init__.py +++ b/prody/database/__init__.py @@ -69,6 +69,33 @@ .. _GOA: https://www.ebi.ac.uk/GOA/ +Swiss-Prot +================================ +The following classes and functions can be used to search and retrieve data from the Swiss-Prot database: + * :class:`.SwissProt` - class to handle Swiss-Prot data from Expasy + * :func:`.getCurrentRelease` - gets current Swiss-Prot release version + * :func:`.downloadRelease` - downloads current Swiss-Prot database files + * :func:`.saveRelease` - saves new Swiss-Prot release version + * :func:`.updateRelease` - updates Swiss-Prot local database + * :func:`.getLocalRelease` - checks local Swiss-Prot release version + * :func:`.checkForUpdates` - checks wheather there is newer Swiss-Prot version than current local one + + RefSeq + ================================ +The following classes and functions can be used to search and retrieve data from the RefSeq database: + * :class:` .RefSeq` - class to handle RefSeq data + * :func:` getCurrentRelease` - func desc + * :func:` getInstalledFiles` - func desc + * :func:` saveInstalledFiles` - func desc + * :func:` getLocalFiles` - func desc + * :func:` getFiles` - func desc + * :func:` pepareDownloadFileList` - func desc + * :func:` downloadRelease` - func desc + * :func:` saveRelease` - func desc + * :func:` updateRelease` - func desc + * :func:` getLocalRelease` - func desc + * :func:` checkForUpdates` - func desc + Interpro ==== @@ -115,6 +142,18 @@ from .quartataweb import * __all__.extend(quartataweb.__all__) +from . import swissprot +from .swissprot import * +__all__.extend(swissprot.__all__) + +from . import refseq +from .refseq import * +__all__.extend(refseq.__all__) + +from . import pdb +from .pdb import * +__all__.extend(pdb.__all__) + from . import interpro from .interpro import * __all__.extend(interpro.__all__) diff --git a/prody/database/pdb.py b/prody/database/pdb.py new file mode 100644 index 000000000..10ba9bfea --- /dev/null +++ b/prody/database/pdb.py @@ -0,0 +1,28 @@ +# -*- coding: utf-8 -*- + +"""Protein Data Bank database operations.""" + +import os + +from prody import LOGGER +from prody.utilities.motifhelpers import downloadFile + +__all__ = ["ProteinDataBank"] + + +class ProteinDataBank: + """Protein Data Bank""" + + @classmethod + def downloadRelease(cls, data_dir: str) -> None: + """Download latest pdb database. + + Args: + data_dir (str): Directory to download to. + """ + url = "https://ftp.wwpdb.org/pub/pdb/derived_data/" + file = "pdb_seqres.txt.gz" + LOGGER.timeit("downloadRelease") + directory = os.path.join(data_dir, cls.__name__) + downloadFile(url, directory, file) + LOGGER.report(msg="downloadRelease completed in %.2fs.", label="downloadRelease") diff --git a/prody/database/refseq.py b/prody/database/refseq.py new file mode 100644 index 000000000..52d7a0742 --- /dev/null +++ b/prody/database/refseq.py @@ -0,0 +1,180 @@ +# -*- coding: utf-8 -*- + +"""RefSeq database operations.""" + +import os +import re +from concurrent.futures import ThreadPoolExecutor + +import requests +import requests_cache +from datetime import timedelta +from prody import LOGGER +from prody.utilities.motifhelpers import downloadFile + +__all__ = ["RefSeq"] + +requests_cache.install_cache(expire_after=timedelta(weeks=1)) + + +class RefSeq: + """RefSeq database.""" + + RELEASE_FILE = "release.txt" + CHECK_SUMS = "files_installed.txt" + + @classmethod + def getCurrentRelease(cls) -> str: + """Get current RefSeq db release version. + + Raises: + Exception: No release version found. + + Returns: + str: RefSeq db release version. + """ + rs_release = "" + url = "https://ftp.ncbi.nlm.nih.gov/refseq/release/RELEASE_NUMBER" + try: + with requests_cache.disabled(): + response = requests.get(url) + except requests.exceptions.RequestException as exception: + LOGGER.error(str(exception)) + else: + rs_release = response.text.strip() + if not re.match(r"\d+", rs_release): + LOGGER.error("Could't determine release version.") + LOGGER.debug("RefSeq current release: {}".format(rs_release)) + return rs_release + + @classmethod + def getInstalledFiles(cls) -> str: + """Reads installed files with corresponding check sums.""" + LOGGER.debug("Downloading installed files with check sums.") + current_release = cls.getCurrentRelease() + url = "https://ftp.ncbi.nlm.nih.gov/refseq/release/release-catalog/release{}.files.installed".format(current_release) + try: + with requests_cache.disabled(): + response = requests.get(url) + except requests.exceptions.RequestException as exception: + LOGGER.error(str(exception)) + else: + result = "" + lines = response.text.split("\n") + for line in lines: + if re.search(r"complete\.(\d+\.){1,2}protein\.faa\.gz", line): + result += line + "\n" + return result + + @classmethod + def saveInstalledFiles(cls, data_dir: str) -> None: + """Saves installed files list with check sums locally.""" + installed_files = cls.getInstalledFiles() + path = os.path.join(data_dir, cls.__name__) + os.makedirs(path, exist_ok=True) + with open("{}/{}".format(path, cls.CHECK_SUMS), "w", encoding="utf-8") as file: + file.write(installed_files) + LOGGER.debug("{} file saved locally.".format(cls.CHECK_SUMS)) + + @classmethod + def getLocalFiles(cls, data_dir: str) -> dict: + """Lists local RefSeq FASTA protein files and corresponding check sums. + + Returns: + dict: file names and corresponding check sums. + """ + LOGGER.debug("Getting local RefSeq protein FASTA files") + path = os.path.join(data_dir, cls.__name__) + os.makedirs(path, exist_ok=True) + filename = os.path.join(path, cls.CHECK_SUMS) + if os.path.exists(filename): + with open(filename, "r", encoding="utf-8") as file: + text = file.read() + results = re.findall(r"^(\d+)\s+(\S+)$", text, re.M) + return {result[1]: result[0] for result in results} + else: + return {} + + @classmethod + def getFiles(cls) -> dict: + """Lists all FASTA protein files on RefSeq ftp server. + + Returns: + dict: FASTA protein files with check sums. + """ + LOGGER.debug("Getting protein FASTA file list from RefSeq.") + installed_files = cls.getInstalledFiles() + file_matcher = re.compile(r"^(\d+)\s+(\S+)$", re.M) + files = re.findall(file_matcher, installed_files) + return {file[1]: file[0] for file in files} if files else {} + + @classmethod + def pepareDownloadFileList(cls, data_dir: str) -> list: + """Prepare file list to be downloaded""" + LOGGER.debug("Preparing file list to be downloaded.") + remote_files = cls.getFiles() + local_files = cls.getLocalFiles(data_dir) + download_list = [] + for filename in remote_files.keys(): + if filename in local_files.keys(): + if remote_files[filename] != local_files[filename]: + download_list.append(filename) + else: + download_list.append(filename) + return download_list + + @classmethod + def downloadRelease(cls, data_dir: str) -> None: + """Download latest RefSeq database release.""" + + def report_done(future): + LOGGER.info("Downloaded file {}".format(future.result())) + + files = cls.pepareDownloadFileList(data_dir) + url = "https://ftp.ncbi.nlm.nih.gov/refseq/release/complete/" + LOGGER.timeit("downloadRelease") + with ThreadPoolExecutor(max_workers=100) as executor: + for file in files: + directory = os.path.join(data_dir, cls.__name__) + future = executor.submit(downloadFile, url, directory, file) + future.add_done_callback(report_done) + LOGGER.report(msg="downloadRelease completed in %.2fs.", label="downloadRelease") + + @classmethod + def saveRelease(cls, data_dir: str) -> None: + """Write current release version to disk.""" + current_release = cls.getCurrentRelease() + path = os.path.join(data_dir, cls.__name__) + os.makedirs(path, exist_ok=True) + with open("{}/{}".format(path, cls.RELEASE_FILE), "w", encoding="utf-8") as file: + file.write(current_release) + LOGGER.debug("RefSeq release {} saved.".format(current_release)) + + @classmethod + def updateRelease(cls, data_dir) -> None: + """Update release to the most recent one.""" + LOGGER.debug("Updating RefSeq release version.") + cls.downloadRelease(data_dir) + cls.saveRelease(data_dir) + + @classmethod + def getLocalRelease(cls, data_dir) -> str: + """Get release version from local disk.""" + path = os.path.join(data_dir, cls.__name__) + os.makedirs(path, exist_ok=True) + version = "" + release = os.path.join(path, cls.RELEASE_FILE) + if os.path.exists(release): + with open(release, "r", encoding="utf-8") as file: + version = file.readline() + LOGGER.debug("RefSeq local release: {}".format(version)) + else: + LOGGER.debug("RefSeq local release not found.") + return version + + @classmethod + def checkForUpdates(cls, data_dir) -> None: + """Check if local version is the recent one.""" + LOGGER.debug("RefSeq checking for updates.") + if cls.getCurrentRelease() != cls.getLocalRelease(data_dir): + cls.updateRelease(data_dir) diff --git a/prody/database/swissprot.py b/prody/database/swissprot.py new file mode 100644 index 000000000..a97c6ae4f --- /dev/null +++ b/prody/database/swissprot.py @@ -0,0 +1,110 @@ +# -*- coding: utf-8 -*- + +"""Swiss-Prot database operations.""" + +import os +import re +import requests +import requests_cache +from datetime import timedelta +from concurrent.futures import ThreadPoolExecutor + +from prody import LOGGER +from prody.utilities.motifhelpers import downloadFile + +__all__ = ["SwissProt"] + +requests_cache.install_cache(expire_after=timedelta(weeks=1)) + + +class SwissProt: + """Swiss-Prot database.""" + + RELEASE_FILE = "release.txt" + HEADERS = {"User-Agent": "Python pattern search agent", "Contact": "mkonstanty@gmail.com"} + + @classmethod + def getCurrentRelease(cls) -> str: + """Get current swiss-prot db release version. + + Raises: + Exception: No release version found. + + Returns: + str: Swiss-prot db release version. + """ + sp_release = "" + url = "https://ftp.expasy.org/databases/swiss-prot/release/reldate.txt" + try: + with requests_cache.disabled(): + response = requests.get(url, headers=cls.HEADERS) + except requests.exceptions.RequestException as exception: + LOGGER.error(str(exception)) + else: + sp_release = re.search(r"Swiss-Prot Release (\d{4}_\d{2})", response.text) + if not sp_release: + LOGGER.error("Could't determine release version.") + LOGGER.debug("Swiss-Prot current release: {}".format(sp_release[1])) + return sp_release[1] + + @classmethod + def downloadRelease(cls, data_dir: str, types=None) -> None: + """Download latest swiss-prot database release. + + Args: + types (list, optional): Database file types. Defaults to None. + """ + + def report_done(future): + LOGGER.info("Downloaded file {}".format(future.result())) + + types = types if types else ["xml", "dat", "fasta"] + files = ["uniprot_sprot.{}.gz".format(type) for type in types] + url = "https://ftp.expasy.org/databases/swiss-prot/release/" + LOGGER.timeit("downloadRelease") + with ThreadPoolExecutor(max_workers=3) as executor: + for file in files: + directory = os.path.join(data_dir, cls.__name__) + future = executor.submit(downloadFile, url, directory, file, headers=cls.HEADERS) + future.add_done_callback(report_done) + LOGGER.report(msg="downloadRelease completed in %.2fs.", label="downloadRelease") + + @classmethod + def saveRelease(cls, data_dir: str) -> None: + """Write current release version to disk.""" + current_release = cls.getCurrentRelease() + path = os.path.join(data_dir, cls.__name__) + os.makedirs(path, exist_ok=True) + with open("{}/{}".format(path, cls.RELEASE_FILE), "w", encoding="utf-8") as file: + file.write(current_release) + LOGGER.debug("Swiss-Prot release {} saved.".format(current_release)) + + @classmethod + def updateRelease(cls, data_dir) -> None: + """Update release to the most recent one.""" + LOGGER.debug("Updating Swiss-Prot release version.") + cls.downloadRelease(data_dir, types=["fasta"]) + cls.saveRelease(data_dir) + + @classmethod + def getLocalRelease(cls, data_dir: str) -> str: + """Get release version from local disk.""" + LOGGER.debug("Getting Swiss-Prot local release version.") + path = os.path.join(data_dir, cls.__name__) + os.makedirs(path, exist_ok=True) + version = "" + release = os.path.join(path, cls.RELEASE_FILE) + if os.path.exists(release): + with open(release, "r", encoding="utf-8") as file: + version = file.readline() + LOGGER.debug("Swiss-Prot local release: {}".format(version)) + else: + LOGGER.debug("Swiss-Prot local release not found.") + return version + + @classmethod + def checkForUpdates(cls, data_dir) -> None: + """Check if local version is the recent one.""" + LOGGER.debug("Swiss-Prot checking for updates.") + if cls.getCurrentRelease() != cls.getLocalRelease(data_dir): + cls.updateRelease(data_dir) diff --git a/prody/sequence/__init__.py b/prody/sequence/__init__.py index 9545bb480..4243de576 100644 --- a/prody/sequence/__init__.py +++ b/prody/sequence/__init__.py @@ -46,10 +46,19 @@ * :func:`.showShannonEntropy` - plot Shannon entropy * :func:`.showMSAOccupancy` - plot row (sequence) or column occupancy * :func:`.showMutinfoMatrix` - show mutual information matrix + + +Searching +======== + * :func:`.getPdbCodesFromMotif` - get PDB code from MOTIF """ __all__ = [] +from . import motif +from .motif import * +__all__.extend(motif.__all__) + from . import msa from .msa import * __all__.extend(msa.__all__) diff --git a/prody/sequence/motif.py b/prody/sequence/motif.py new file mode 100644 index 000000000..444c55d4f --- /dev/null +++ b/prody/sequence/motif.py @@ -0,0 +1,491 @@ +# -*- coding: utf-8 -*- + +"""This module prase protein sequences using PROSITE motifs.""" + +import os +import re +import requests +import requests_cache +from datetime import timedelta +import json +from typing import Optional + +from prody import LOGGER +from prody.utilities.motifhelpers import prositeToRegEx, openFile + + +__all__ = [ + "getUniprot", + "getPdbCodesFromMotif", + "saveMotifResults", + "expasySearchMotif", + "spOnlineMotifSearch", + "pdbOnlineMotifSearch", + "localMotifSearch", + "spLocalMotifSearch", + "pdbLocalMotifSearch", + "motifSearch", +] + +MOTIF_PATTERN = ( + r"^([ARDNCEQGHILKMFPSTWYVx]*" + r"(\[[ARDNCEQGHILKMFPSTWYV]+\])*" + r"({{[{{ARDNCEQGHILKMFPSTWYV}}]+}})*" + r"([ARDNCEQGHILKMFPSTWYVx]\(\d(,\d)?\))*)+$" +) +MOTIF_MATCHER = re.compile(MOTIF_PATTERN) + +requests_cache.install_cache(expire_after=timedelta(weeks=1)) + + +def getUniprot(id: str) -> str: + """Get details for accession key from UniProt + + Args: + id (str): Uniprot accession key + + Returns: + str: details + """ + LOGGER.debug("Get {} details from Uniprot.".format(id)) + headers = {"User-Agent": "Python pattern search agent", "Contact": "mkonstanty@gmail.com"} + url = "https://www.uniprot.org/uniprot/{}.txt".format(id) + try: + response = requests.get(url, headers=headers) + except requests.exceptions.RequestException as exception: + LOGGER.error(str(exception)) + result = response.text.replace("\n", "<\\br>") + return result + + +def getPdbCodesFromMotif(motif: str, results: Optional[int] = None, page: Optional[int] = None) -> list: + """Get PDB code from motif. + + Args: + motif (str): FASTA motif + results (Optional[int], optional): How many results to return. Defaults to None. + page (Optional[int], optional): Which result page to return. Defaults to None. + + Returns: + list: PDB ids + """ + LOGGER.debug("Get PDB code from motif {}".format(motif)) + url = "https://search.rcsb.org/rcsbsearch/v2/query" + headers = {"Content-Type": "application/json;charset=utf-8"} + if results and page: + paginate = {"paginate": {"start": results * (page - 1), "rows": results * page - 1}} + else: + paginate = {"return_all_hits": True} + data = { + "return_type": "entry", + "query": { + "type": "terminal", + "service": "seqmotif", + "parameters": {"value": motif, "pattern_type": "prosite", "target": "pdb_protein_sequence"}, + }, + "request_options": paginate, + } + try: + LOGGER.timeit("getPdbCodesFromMotif") + response = requests.post(url, headers=headers, data=json.dumps(data)) + LOGGER.debug("Result taken from cache: {}".format(response.from_cache)) + LOGGER.report(msg="getPdbCodesFromMotif completed in %.2fs.", label="getPdbCodesFromMotif") + except requests.exceptions.RequestException as exception: + LOGGER.error(str(exception)) + else: + response.encoding = "UTF-8" + result = json.loads(response.text) + result["result_set"] + return [x["identifier"] for x in result["result_set"]] + + +def saveMotifResults(database: str, motif: str, data: list[dict], directory: str) -> str: + """Save search data to a file. + + Args: + database (str): name of the database + motif (str): FASTA motif + data (list[dict]): List of proteins to be saved. + directory (str): directory to save results + + Returns: + str: saved file name + """ + os.makedirs(directory, exist_ok=True) + filename = "{}_{}.txt".format(motif.replace('-', ''), database) + with open("{}/{}".format(directory, filename), "w", encoding="utf-8") as file: + for protein in data: + for key, value in protein.items(): + file.write("{}: {}\n".format(key, value)) + file.write("\n") + LOGGER.info("Search written to a file {}.".format(filename)) + return filename + + +def _expasySPMotifToStructure(response: str) -> list: + """Parse HTML response from Expasy. + + Args: + response (str): HTML response from Expasy + + Returns: + list: List of result dicts + """ + LOGGER.timeit("_expasySPMotifToStructure") + RESULT_PATTERN = ( + r">sp\|" # database + r"(\w+)\|(\w+).*\n" # accession and id + r"(.*)\n" # description + r"([ARDNCEQGHILKMFPSTWYVx\n]+)\W+" # sequence + r"(\d{,3}) - (\d{,3}):\W+(\w+)" # start, end and match + ) + motifs = re.compile(RESULT_PATTERN, re.M) + results = re.findall(motifs, response) + structure = [] + keys = ("accession", "id", "description", "sequence", "start", "end", "match") + for result in results: + structure.append(dict(zip(keys, result))) + LOGGER.report(msg="_expasySPMotifToStructure completed in %.2fs.", label="_expasySPMotifToStructure") + return structure + + +def _expasyPDBMotifToStructure(response: str) -> list: + """Parse HTML response from Expasy. + + Args: + response (str): HTML response from Expasy + + Returns: + list: List of result dicts + """ + LOGGER.timeit("_expasyPDBMotifToStructure") + structure = [] + RESULT_PATTERN = ( + r">pdb\|(\w+).*\n" # pdb id + r".*?((\w+\|\w+[,.])+)\n" # accession and uniprot id + r"\W+(\d{,3}) - (\d{,3}):\W+(\w+)" # start, end and match + ) + motifs = re.compile(RESULT_PATTERN, re.M) + results = re.findall(motifs, response) + for result in results: + pdb_id, tmp, _, start, end, match = result + accessions_ids = dict(re.findall(r"(\w+)\|(\w+)", tmp)) + accessions = ", ".join(accessions_ids.keys()) + ids = ", ".join(accessions_ids.values()) + structure.append( + { + "PDB id": pdb_id, + "Accession ids": accessions, + "UniProt ids": ids, + "start": start, + "end": end, + "match": match, + } + ) + LOGGER.report(msg="_expasyPDBMotifToStructure completed in %.2fs.", label="_expasyPDBMotifToStructure") + return structure + + +def expasySearchMotif(motif: str, database: str) -> list: + """Search motif in remote Swiss-Prot database. + + https://prosite.expasy.org/scanprosite/scanprosite_doc.html#rest_intro + + Args: + motif (str): Motif in PROSITE format. + database (str): 'sp' (UniProtKB/Swiss-Prot) or 'tr' (UniProtKB/TrEMBL) or 'pdb' (PDB). + + Returns: + list: List of result dicts + """ + + def err(*args) -> list: + return [] + + LOGGER.debug("Searching motif {} in {} database via Expasy".format(motif, database)) + headers = {"User-Agent": "Python pattern search agent", "Contact": "mkonstanty@gmail.com"} + url = "https://prosite.expasy.org/cgi-bin/prosite/PSScan.cgi" + payload = {"sig": motif, "db": database} + try: + LOGGER.timeit("expasySearchMotif") + result = requests.get(url, params=payload, headers=headers) + LOGGER.debug("Result taken from cache: {}".format(result.from_cache)) + LOGGER.report(msg="expasySearchMotif completed in %.2fs.", label="expasySearchMotif") + except Exception as exception: + LOGGER.error("Remote search for motif {} in Swiss-Prot database failed: {}".format(motif, exception)) + else: + return {"sp": _expasySPMotifToStructure, "pdb": _expasyPDBMotifToStructure,}.get( + database, err + )(result.text) + + +def spOnlineMotifSearch(motif: str, *args) -> list: + """Search motif in remote Swiss-Prot database. + + Args: + motif (str): Motif in PROSITE format. + + Returns: + list: List of result dicts + """ + LOGGER.debug("Search for motif in Swiss-Prot online.") + return expasySearchMotif(motif, "sp") + + +def rsOnlineMotifSearch(motif: str, *args) -> list: + """ "Search motif in remote RefSeq database. + + Args: + motif (str): Motif in PROSITE format. + + Raises: + NotImplementedError: not implemented yet + + Returns: + list: List of result dicts + """ + LOGGER.debug("Search for motif in RefSeq online.") + # return remoteSearchMotif(motif, "refseq") + raise NotImplementedError + + +def pdbOnlineMotifSearch(motif: str, *args) -> list: + """Search motif in remote PDB database. + + + Args: + motif (str): Motif in PROSITE format. + + Returns: + list: list: List of result dicts + """ + LOGGER.debug("Search for motif in Protein Data Bank online.") + return expasySearchMotif(motif, "pdb") + + +def _defaultParse(pattern: str, protein: list) -> list: + """Parse protein sequence. + + Args: + pattern (str): motif regex + protein (list): FASTA protein + + Returns: + Optional[list]: Parsed protein. + """ + description = protein[0].replace(">", "") + sequence = "".join(protein[1:]).replace("\n", "") + motif_matcher = re.compile(pattern) + results = re.finditer(motif_matcher, sequence) + elements = [] + for result in results: + elements.append( + { + "description": description, + "sequence": sequence, + "start": result.start(), + "end": result.end(), + "match": result.group(0), + } + ) + return elements + + +def _spParse(pattern: str, protein: list) -> list: + """Parse Swiss-Prot protein sequence. + + Args: + pattern (str): motif regex + protein (list): FASTA protein + + Returns: + Optional[list]: Parsed protein. + """ + line = protein[0].replace(">", "").replace("\n", "") + sequence = "".join(protein[1:]).replace("\n", "") + tmp = line.split(" ") + _, accession, id = tmp[0].split("|") + description = " ".join(tmp[1:]) if id else line + motif_matcher = re.compile(pattern) + results = re.finditer(motif_matcher, sequence) + elements = [] + for result in results: + elements.append( + { + "accession": accession, + "id": id, + "description": description, + "sequence": sequence, + "start": result.start(), + "end": result.end(), + "match": result.group(0), + } + ) + return elements + + +def _rsParse(pattern: str, protein: list) -> list: + """Parse RefSeq protein sequence. + + Args: + pattern (str): motif regex + protein (list): FASTA protein + + Returns: + Optional[list]: Parsed protein. + """ + raise NotImplementedError + + +def _pdbParse(pattern: str, protein: list) -> list: + """Parse Protein Data Bank protein sequence. + + Args: + pattern (str): motif regex + protein (list): FASTA protein + + Returns: + Optional[list]: Parsed protein. + """ + elements = [] + line = protein[0].replace(">", "") + sequence = "".join(protein[1:]) + pdb_id, mol, length, *description = re.split(r"\s+", line) + if "protein" not in mol: + return elements + length = length.split(":")[1] + motif_matcher = re.compile(pattern) + results = re.finditer(motif_matcher, sequence) + for result in results: + elements.append( + { + "PDB id": pdb_id, + "Description": " ".join(description), + "Protein length": length, + "sequence": sequence, + "start": result.start(), + "end": result.end(), + "match": result.group(0), + } + ) + return elements + + +def localMotifSearch(filename: str, motif: str, parse: str) -> list: + """Search for motif in local database file. + + Args: + filename (str): path to filename + motif (str): PROSITE motif + + Returns: + list: Parsed proteins + """ + data = [] + LOGGER.timeit("localMotifSearch") + pattern = prositeToRegEx(motif) + protein = [] + try: + file = openFile(filename) + line = file.readline() + if line.startswith(">"): + protein.append(line) + else: + LOGGER.error("Only FASTA files supported.") + for line in file: + if line.startswith(">"): + data.extend( + {"sp": _spParse, "rs": _rsParse, "pdb": _pdbParse,}.get( + parse, _defaultParse + )(pattern, protein) + ) + protein.clear() + protein.append(line) + else: + protein.append(line) + except Exception as e: + LOGGER.error(str(e)) + finally: + file.close() + LOGGER.report(msg="localMotifSearch completed in %.2fs.", label="localMotifSearch") + return data + + +def spLocalMotifSearch(motif: str, data_dir: str) -> list: + """Search for motif in local Swiss-Prot database file. + + Args: + motif (str): PROSITE motif + data_dir (str): local Swiss-Prot database directory + Returns: + list: Parsed proteins + """ + LOGGER.debug("Running local Swiss-Prot motif search...") + filename = os.path.join(data_dir, "SwissProt/uniprot_sprot.fasta.gz") + return localMotifSearch(filename, motif, "sp") + + +def rsLocalMotifSearch(motif: str, data_dir: str) -> list: + """Search for motif in local RefSeq database file. + + Args: + motif (str): PROSITE motif + data_dir (str): local RefSeq database directory + upload_dir (str): directory for local custom databases + + Raises: + NotImplementedError: not implemented yet + + Returns: + list: list: Parsed proteins + """ + LOGGER.debug("Running local RefSeq motif search...") + raise NotImplementedError + + +def pdbLocalMotifSearch(motif: str, data_dir: str) -> list: + """Search for motif in local PDB database file. + + Args: + motif (str): PROSITE motif + data_dir (str): local RefSeq database directory + upload_dir (str): directory for local custom databases + + Raises: + NotImplementedError: not implemented yet + + Returns: + list: Parsed proteins + """ + LOGGER.debug("Running local ProteinDataBank motif search...") + filename = os.path.join(data_dir, "ProteinDataBank/pdb_seqres.txt.gz") + return localMotifSearch(filename, motif, "pdb") + + +def motifSearch(database: str, motif: str, data_dir: str) -> Optional[list]: + """Search for motif in protein database. + + Args: + database (str): selected database + motif (str): motif to be searched + data_dir (str): local builin database directory + upload_dir (str): local custom database directory + + Returns: + Optional[list]: Parsed proteins + """ + + def custom(motif: str, data_dir: str) -> Optional[list]: + LOGGER.debug("Running local motif search...") + filename = os.path.join(data_dir, "local", database) + return localMotifSearch(filename, motif, "default") + + LOGGER.debug("Motif search:\t{}\t{}".format(database, motif)) + return { + "sp-online": spOnlineMotifSearch, + "rs-online": rsOnlineMotifSearch, + "pdb-online": pdbOnlineMotifSearch, + "sp-local": spLocalMotifSearch, + "rs-local": rsLocalMotifSearch, + "pdb-local": pdbLocalMotifSearch, + }.get(database, custom)(motif, data_dir) diff --git a/prody/tests/sequence/test_motif.py b/prody/tests/sequence/test_motif.py new file mode 100644 index 000000000..0002205e4 --- /dev/null +++ b/prody/tests/sequence/test_motif.py @@ -0,0 +1,102 @@ +from prody import LOGGER, _expasyMotifToStructure, expasySearchMotif +from prody.tests import TestCase + +LOGGER.verbosity = None + + +EXPASY_SCAN_PROSITE_TOOL_RESPONSE = """
include splice variants (Swiss-Prot)
+Output format: Text
+
+Hits for USERPAT1'P-x(2)-G-E-S-G(2)-[AS]'  motif on UniProtKB/Swiss-Prot sequences:
+UniProtKB/Swiss-Prot (Release 2022_01 of 23-Feb-22) contains 566,996 entries.
+
+found: 11 hits in 11 sequences
+
+Graphical view (graphical view with feature detection)
+shaded alignment of hits
+
+ :
+   >USERPAT1 (user pattern) :
+   Pattern: P-x(2)-G-E-S-G(2)-[AS]
+   Approximate number of expected random matches in ~ 100'000 sequences (50'000'000 residues): 0.44
+
+
+>sp|Q3SYW2|CO2_BOVIN  (750 aa)
+Complement C2 (EC 3.4.21.43) (C3/C5 convertase) [Cleaved into: Complement C2b fragment; Complement C2a fragment].  [Bos taurus (Bovine)]
+MDPLMAVLCLLPLYPGLATAALSCPKNVNISGGSFTLSNGWNPGSILTYSCPLGHYPYPVVTRLCKSNGQWQIPRSTRST
+KAICKPVRCPAPVSFENGVYIPRLGSHPVGGNLSFECEDGFTLRGSAVRQCRPNGMWDGETAVCDNGASHCPNPGISVGA
+VRTGSRFGLGDKVRYRCSSNLVLTGSAERECQDDGVWSGTEAICRQPYSYDFPEDVAPALGTSFSHLLATTNPIQQKKKQ
+NLGRKIQIQRSGHLNLYLLLDASQSVSKDDFEIFKDSASRMVDRIFSFEIKVSVAIITFASKPKIIMSVLEDRSRDVTEV
+ENSLRNINYKDHENGTGTNIYEALHAVYIMMNNQMNRPHMNPGAWQEIRHAIILLTDGKSNMGGSPKVAVDNIKEVLNIN
+QKRKDYLDIYAIGVGSLHVDWKELNNLGSKKDGERHAFILKDVQALSQVFEHMLDVSQLTDPICGVGNMSANASAQERTP
+WHVTIKPKSQETCRGALISDQWVLTAAHCFRNAEDRTLWRVSVGDPNFQGSKEFQIEEAVISPGFNVFSKKSQGIPEFYG
+DDIALLKLTQKVKMSTHARPICLPCTVGANLALRKLPGSTCRDHEKELLNQVSIPAHFVALNGDKLNINLKTGSEWTNCV
+KVVLKDKTTFPNLTDVREVVTDQFLCSGTQGDDSPCKGESGGAVFLERRLRFFQVGLVSWGLYNPCGGSSKNSRKPAPHG
+KVPRDFHINLFRLQPWLRQHLEGILNFVPL
+      675 - 683:      PckGESGGA
+
+
+>sp|Q863A0|CO2_GORGO  (752 aa)
+Complement C2 (EC 3.4.21.43) (C3/C5 convertase) [Cleaved into: Complement C2b fragment; Complement C2a fragment].  [Gorilla gorilla gorilla (Western lowland gorilla)]
+MGPLMVLFCLLFVYTGLADSAPSCPQNVNISGGTFTLSHGWAPGSLLTYSCPQGLYPSPASRLCKSSGQWQTPGATRSLS
+KAVCKPVRCPAPVSFENGIYTPRLGSYPVGGNVSFECEDGFILRGSPVRQCRPNGMWDGETAVCDNGAGHCPNPGISLGA
+VRTGFRFGHGDKVRYRCSSNLVLTGSSERECQGNGVWSGTEPICRQPYSYDFPEDVAPALGTSFSHMLGATNPTQKTKES
+LGRKIQIQRSGHLNLYLLLDCSQSVSENDFLIFKESASLMVDRIFSFEINVSVAIITFASKPKVLMSVLNDNSRDMTEVI
+SSLENANYKDHENGTGTNTYAALNSVYLMMNNQMRILGMETMAWQEIRHAIILLTDGKSNMGGSPKTAVDRIREILNINQ
+KRNDYLDIYAIGVGKLDVDWRELNELGSKKDGERHAFILQDTKALHQVFEHMLDVSKLTDTICGVGNMSANASDQERTPW
+HVTIKPKSQETCRGALISDQWVLTAAHCFRDGNDHSLWRVNVGDPKSQWGKEFLIEKAVISPGFDVFAKKNQGILEFYGD
+DIALLKLAQKVKMSTHARPICLPCTMEANLALRRPQGSTCRDHENELLNKQSVPAHFVALNGSKLNINLKMGVEWTSCAE
+VVSQEKTMFPNLTDVREVVTDQFLCSGTQEDESPCKGESGGAVFLERRFRFFQVGLVSWGLYNPCLGSADKNSRKRAPRS
+KVPPPRDFHINLFRMQPWLRQHLGDVLNFLPL
+      674 - 682:      PckGESGGA
""" + +EXPASY_SCAN_PROSITE_TOOL_RESULT = [ + { + "database": "sp", + "accession": "Q3SYW2", + "id": "CO2_BOVIN", + "description": "Complement C2 (EC 3.4.21.43) (C3/C5 convertase) [Cleaved into: Complement C2b fragment; Complement C2a fragment]. [Bos taurus (Bovine)]", + "sequence": "MDPLMAVLCLLPLYPGLATAALSCPKNVNISGGSFTLSNGWNPGSILTYSCPLGHYPYPVVTRLCKSNGQWQIPRSTRST" + "KAICKPVRCPAPVSFENGVYIPRLGSHPVGGNLSFECEDGFTLRGSAVRQCRPNGMWDGETAVCDNGASHCPNPGISVGA" + "VRTGSRFGLGDKVRYRCSSNLVLTGSAERECQDDGVWSGTEAICRQPYSYDFPEDVAPALGTSFSHLLATTNPIQQKKKQ" + "NLGRKIQIQRSGHLNLYLLLDASQSVSKDDFEIFKDSASRMVDRIFSFEIKVSVAIITFASKPKIIMSVLEDRSRDVTEV" + "ENSLRNINYKDHENGTGTNIYEALHAVYIMMNNQMNRPHMNPGAWQEIRHAIILLTDGKSNMGGSPKVAVDNIKEVLNIN" + "QKRKDYLDIYAIGVGSLHVDWKELNNLGSKKDGERHAFILKDVQALSQVFEHMLDVSQLTDPICGVGNMSANASAQERTP" + "WHVTIKPKSQETCRGALISDQWVLTAAHCFRNAEDRTLWRVSVGDPNFQGSKEFQIEEAVISPGFNVFSKKSQGIPEFYG" + "DDIALLKLTQKVKMSTHARPICLPCTVGANLALRKLPGSTCRDHEKELLNQVSIPAHFVALNGDKLNINLKTGSEWTNCV" + "KVVLKDKTTFPNLTDVREVVTDQFLCSGTQGDDSPCKGESGGAVFLERRLRFFQVGLVSWGLYNPCGGSSKNSRKPAPHG" + "KVPRDFHINLFRLQPWLRQHLEGILNFVPL", + "start": "675", + "end": "683", + "match": "PckGESGGA", + }, + { + "database": "sp", + "accession": "Q863A0", + "id": "CO2_GORGO", + "description": "Complement C2 (EC 3.4.21.43) (C3/C5 convertase) [Cleaved into: Complement C2b fragment; Complement C2a fragment]. [Gorilla gorilla gorilla (Western lowland gorilla)]", + "sequence": "MGPLMVLFCLLFVYTGLADSAPSCPQNVNISGGTFTLSHGWAPGSLLTYSCPQGLYPSPASRLCKSSGQWQTPGATRSLS" + "KAVCKPVRCPAPVSFENGIYTPRLGSYPVGGNVSFECEDGFILRGSPVRQCRPNGMWDGETAVCDNGAGHCPNPGISLGA" + "VRTGFRFGHGDKVRYRCSSNLVLTGSSERECQGNGVWSGTEPICRQPYSYDFPEDVAPALGTSFSHMLGATNPTQKTKES" + "LGRKIQIQRSGHLNLYLLLDCSQSVSENDFLIFKESASLMVDRIFSFEINVSVAIITFASKPKVLMSVLNDNSRDMTEVI" + "SSLENANYKDHENGTGTNTYAALNSVYLMMNNQMRILGMETMAWQEIRHAIILLTDGKSNMGGSPKTAVDRIREILNINQ" + "KRNDYLDIYAIGVGKLDVDWRELNELGSKKDGERHAFILQDTKALHQVFEHMLDVSKLTDTICGVGNMSANASDQERTPW" + "HVTIKPKSQETCRGALISDQWVLTAAHCFRDGNDHSLWRVNVGDPKSQWGKEFLIEKAVISPGFDVFAKKNQGILEFYGD" + "DIALLKLAQKVKMSTHARPICLPCTMEANLALRRPQGSTCRDHENELLNKQSVPAHFVALNGSKLNINLKMGVEWTSCAE" + "VVSQEKTMFPNLTDVREVVTDQFLCSGTQEDESPCKGESGGAVFLERRFRFFQVGLVSWGLYNPCLGSADKNSRKRAPRS" + "KVPPPRDFHINLFRMQPWLRQHLGDVLNFLPL", + "start": "674", + "end": "682", + "match": "PckGESGGA", + }, +] + +EXPASY_ERROR = '

ERROR: Invalid characters in pattern "aaaaaa".

' + + +class TestMotif(TestCase): + def testExpasyTextToStructure(self): + self.assertEqual(_expasyMotifToStructure(EXPASY_SCAN_PROSITE_TOOL_RESPONSE), EXPASY_SCAN_PROSITE_TOOL_RESULT) + + def testEmptyExpasyStructure(self): + self.assertEqual(_expasyMotifToStructure(EXPASY_ERROR), []) diff --git a/prody/utilities/__init__.py b/prody/utilities/__init__.py index 9bb73a255..92f8f5cae 100644 --- a/prody/utilities/__init__.py +++ b/prody/utilities/__init__.py @@ -73,6 +73,7 @@ from .seqtools import * from .TreeConstruction import * from .eigtools import * +from .motifhelpers import * from . import catchall from .catchall import * diff --git a/prody/utilities/motifhelpers.py b/prody/utilities/motifhelpers.py new file mode 100644 index 000000000..7fafff48d --- /dev/null +++ b/prody/utilities/motifhelpers.py @@ -0,0 +1,166 @@ +# -*- coding: utf-8 -*- + +"""This module defines functions and constants related to MOTIF.""" + +from typing import Any, Optional +import re +import os +import requests +import requests_cache +from datetime import timedelta +from .logger import LOGGER + +__all__ = [ + "prositeToRegEx", + "validateMotif", + "downloadFile", + "openFile", + "getLocalDBs", + "getGenericDBs", +] + +CHUNK_SIZE = 16 * 1024 + +requests_cache.install_cache(expire_after=timedelta(weeks=1)) + + +def prositeToRegEx(motif: str) -> str: + """Change PROSITE Motif to python regular expression. + + Args: + pattern (str): PROSITE Motif + + Returns: + str: regular expression + """ + pattern = ( + motif.replace("{", "[^") + .replace("}", "]") + .replace("(", "{") + .replace(")", "}") + .replace("-", "") + .replace("x", ".") + .replace(">", "$") + .replace("<", "*") + ) + return pattern + + +def validateMotif(prosite: str) -> bool: + """_summary_ + + Args: + prosite (str): _description_ + + Returns: + bool: _description_ + """ + motif = prosite.replace("-", "") + motif_pattern = r"^([ARDNCEQGHILKMFPSTWYVx]*(\[[ARDNCEQGHILKMFPSTWYV]+\])*({{[{{ARDNCEQGHILKMFPSTWYV}}]+}})*([ARDNCEQGHILKMFPSTWYVx]\(\d(,\d)?\))*)+$" # noqa + motif_matcher = re.compile(motif_pattern) + matcher = re.match(motif_matcher, motif) + return True if matcher else False + + +def downloadFile(url: str, dir: str, file: str, **kwargs: Any) -> str: + """Downloads a file via http protocol. + + Args: + url (str): file url for download + dir (str): directory to download to + file (str): filename to download + kwargs (Any): keyword arguments for GET request + """ + kwargs.update({"stream": True}) + LOGGER.info("Downloading file {}.".format(file)) + os.makedirs(dir, exist_ok=True) + try: + with requests_cache.disabled(): + with requests.get(url + file, **kwargs) as request: + with open(os.path.join(dir, file), "wb") as output: + for chunk in request.iter_content(chunk_size=CHUNK_SIZE): + output.write(chunk) + except requests.exceptions.RequestException as exception: + LOGGER.error(str(exception)) + return file + + +def _getCompressionType(filename: str) -> Optional[str]: + """Attempts to guess the compression (if any) on a file using the first few bytes. + + Args: + filename (str): file to analize compression type + + Returns: + Optional[str]: compression type + """ + magic_dict = { + "gz": (b"\x1f", b"\x8b", b"\x08"), + "bz2": (b"\x42", b"\x5a", b"\x68"), + "zip": (b"\x50", b"\x4b", b"\x03", b"\x04"), + } + max_len = max(len(x) for x in magic_dict) + with open(filename, "rb") as unknown_file: + file_start = unknown_file.read(max_len) + compression_type = None + for file_type, magic_bytes in magic_dict.items(): + if file_start.startswith(magic_bytes): + compression_type = file_type + return compression_type + + +def openFile(filename: str) -> Any: + """Open file and return handler. + + Args: + filename (str): file to open + + Raises: + NotImplementedError: compression not supported + + Returns: + Any: file handler + """ + compression = _getCompressionType(filename) + if compression == "gz": + import gzip + + return gzip.open(filename, "rt") + elif not compression: + return open(filename, "r") + else: + raise NotImplementedError + + +def getLocalDBs(upload_dir: str) -> list: + """Get all local custom databases. + + Args: + upload_dir (str): Directory to search + + Returns: + list: databases + """ + return os.listdir(upload_dir) + + +def getGenericDBs(data_dir: str) -> dict: + """Get all buildin databases. + + Args: + data_dir (str): Directory to search + + Returns: + dict: databases + """ + result = {} + sp = "{}/SwissProt/release.txt".format(data_dir) + if os.path.isfile(sp): + result.update({"sp-local": "Swiss-Prot (local, buildin)"}) + rs = "{}/RefSeq/release.txt".format(data_dir) + if os.path.isfile(rs): + result.update({"rs-local": "RefSeq (local, buildin)"}) + pdb = "{}/ProteinDataBank/pdb_seqres.txt.gz".format(data_dir) + if os.path.isfile(pdb): + result.update({"pdb-local": "Protein Data Bank (local, buildin)"}) + return result diff --git a/pyproject.toml b/pyproject.toml index b0d88ed49..ffc2b96d2 100644 --- a/pyproject.toml +++ b/pyproject.toml @@ -48,6 +48,8 @@ dependencies = [ "biopython", "pyparsing<=3.1.1", "scipy", + "requests", + "requests_cache", ] [project.urls] diff --git a/scripts/motif_search/app.py b/scripts/motif_search/app.py new file mode 100755 index 000000000..0d24a93b5 --- /dev/null +++ b/scripts/motif_search/app.py @@ -0,0 +1,116 @@ +#!/usr/bin/env python +# -*- coding: utf-8 -*- + +import os +from flask import Flask, render_template, request, send_file, abort, redirect, url_for, flash +from markupsafe import escape +from werkzeug.utils import secure_filename +from prody.sequence.motif import motifSearch, saveMotifResults, getUniprot +from prody.database.swissprot import SwissProt +from prody.database.refseq import RefSeq +from prody.database.pdb import ProteinDataBank +from prody.utilities.motifhelpers import validateMotif, getLocalDBs, getGenericDBs + + +app = Flask(__name__) +app.config.from_pyfile("./config.py") +app.static_folder = app.config.get("STATIC_DIR") + + +@app.route("/", methods=["GET", "POST"]) +def index(): + data_dir = app.config.get("DATA_DIR", "./data") + upload_dir = os.path.join(data_dir, "local") + os.makedirs(upload_dir, exist_ok=True) + if request.method == "POST": + if "file" not in request.files: + flash("No file was uploaded.") + return redirect(request.url) + file = request.files["file"] + if file.filename == "": + flash("Please select a file before upload.") + return redirect(request.url) + filename = secure_filename(file.filename) + file.save(os.path.join(upload_dir, filename)) + flash("File {} uploaded.".format(file)) + return redirect(request.url) + generic_dbs = getGenericDBs(data_dir) + local_dbs = getLocalDBs(upload_dir) + return render_template("index.html", generic_dbs=generic_dbs, local_dbs=local_dbs) + + +@app.route("/searchMotif") +def searchMotif(): + static_dir = app.config.get("STATIC_DIR", "./static") + data_dir = app.config.get("DATA_DIR", "./data") + upload_dir = os.path.join(data_dir, "local") + os.makedirs(upload_dir, exist_ok=True) + motif = str(escape(request.args.get("motif", default=None, type=str))) + if not validateMotif(motif): + flash('"{}" is not PROSITE motif.'.format(motif)) + return redirect(url_for("index")) + database = str(escape(request.args.get("database", default=None, type=str))) + try: + data = motifSearch(database, motif, data_dir) + except: + abort(404) + if data: + filename = saveMotifResults(database, motif, data, static_dir) + flash("Results saved to {}".format(filename)) + else: + flash("No {} pattern found in {}".format(motif, database)) + return redirect(url_for("index")) + local_dbs = getLocalDBs(upload_dir) + generic_dbs = getGenericDBs(data_dir) + return render_template( + "search.html", + generic_dbs=generic_dbs, + local_dbs=local_dbs, + data=data, + filename=filename, + motif=motif, + ) + + +@app.route("/result/") +def download_result(file): + filename = escape(file) + download = "{}/{}".format(app.config.get('STATIC_DIR'), filename) + try: + flash("File {} has been downloaded.".format(filename)) + return send_file(download, as_attachment=True) + except: + abort(404) + + +@app.route("/download/") +def download_database(database): + db = escape(database) + + def err(*args): + abort(404) + + {"sp": SwissProt.checkForUpdates, "rs": RefSeq.checkForUpdates, "pdb": ProteinDataBank.downloadRelease,}.get( + db, err + )(app.config.get("DATA_DIR")) + flash("Database {} successfully downloaded!".format(database)) + return redirect(url_for("index")) + + +@app.route("/alignment/sequence") +def sequence_alignment(): + abort(404) + + +@app.route("/alignment/structural") +def structural_alignment(): + abort(404) + + +@app.errorhandler(404) +def page_not_found(error): + return render_template("404.html") + + +if __name__ == "__main__": + app.run(host="127.0.0.1", port=5080, debug=True) diff --git a/scripts/motif_search/config.py b/scripts/motif_search/config.py new file mode 100644 index 000000000..f21590515 --- /dev/null +++ b/scripts/motif_search/config.py @@ -0,0 +1,10 @@ +"""Flask default configuration.""" + +FLASK_APP = "app" +SECRET_KEY = "efcdc4d982e458f1d116429c" +FLASK_ENV = "production" +DEBUG = False +TESTING = False +DATA_DIR = "./data" +STATIC_DIR = "./static" +UPLOAD_DIR = DATA_DIR + "/local" diff --git a/scripts/motif_search/requirements.txt b/scripts/motif_search/requirements.txt new file mode 100755 index 000000000..dfe4a489b --- /dev/null +++ b/scripts/motif_search/requirements.txt @@ -0,0 +1,7 @@ +flask +requests +requests_cache +biopython<=1.76 +Numpy>=1.10 +pyparsing +scipy \ No newline at end of file diff --git a/scripts/motif_search/run.sh b/scripts/motif_search/run.sh new file mode 100755 index 000000000..82c591a3c --- /dev/null +++ b/scripts/motif_search/run.sh @@ -0,0 +1 @@ +flask run --host 0.0.0.0 --port 5000 diff --git a/scripts/motif_search/static/css/bootstrap.min.css b/scripts/motif_search/static/css/bootstrap.min.css new file mode 100644 index 000000000..6f93a18ed --- /dev/null +++ b/scripts/motif_search/static/css/bootstrap.min.css @@ -0,0 +1,7 @@ +@charset "UTF-8";/*! + * Bootstrap v5.2.0-beta1 (https://getbootstrap.com/) + * Copyright 2011-2022 The Bootstrap Authors + * Copyright 2011-2022 Twitter, Inc. + * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE) + 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1px);--bs-accordion-btn-padding-x:1.25rem;--bs-accordion-btn-padding-y:1rem;--bs-accordion-btn-color:var(--bs-body-color);--bs-accordion-btn-bg:var(--bs-accordion-bg);--bs-accordion-btn-icon:url("data:image/svg+xml,%3csvg xmlns='http://www.w3.org/2000/svg' viewBox='0 0 16 16' fill='var%28--bs-body-color%29'%3e%3cpath fill-rule='evenodd' d='M1.646 4.646a.5.5 0 0 1 .708 0L8 10.293l5.646-5.647a.5.5 0 0 1 .708.708l-6 6a.5.5 0 0 1-.708 0l-6-6a.5.5 0 0 1 0-.708z'/%3e%3c/svg%3e");--bs-accordion-btn-icon-width:1.25rem;--bs-accordion-btn-icon-transform:rotate(-180deg);--bs-accordion-btn-icon-transition:transform 0.2s ease-in-out;--bs-accordion-btn-active-icon:url("data:image/svg+xml,%3csvg xmlns='http://www.w3.org/2000/svg' viewBox='0 0 16 16' fill='%230c63e4'%3e%3cpath fill-rule='evenodd' d='M1.646 4.646a.5.5 0 0 1 .708 0L8 10.293l5.646-5.647a.5.5 0 0 1 .708.708l-6 6a.5.5 0 0 1-.708 0l-6-6a.5.5 0 0 1 0-.708z'/%3e%3c/svg%3e");--bs-accordion-btn-focus-border-color:#86b7fe;--bs-accordion-btn-focus-box-shadow:0 0 0 0.25rem rgba(13, 110, 253, 0.25);--bs-accordion-body-padding-x:1.25rem;--bs-accordion-body-padding-y:1rem;--bs-accordion-active-color:#0c63e4;--bs-accordion-active-bg:#e7f1ff}.accordion-button{position:relative;display:flex;align-items:center;width:100%;padding:var(--bs-accordion-btn-padding-y) var(--bs-accordion-btn-padding-x);font-size:1rem;color:var(--bs-accordion-btn-color);text-align:left;background-color:var(--bs-accordion-btn-bg);border:0;border-radius:0;overflow-anchor:none;transition:var(--bs-accordion-transition)}@media (prefers-reduced-motion:reduce){.accordion-button{transition:none}}.accordion-button:not(.collapsed){color:var(--bs-accordion-active-color);background-color:var(--bs-accordion-active-bg);box-shadow:inset 0 calc(var(--bs-accordion-border-width) * -1) 0 var(--bs-accordion-border-color)}.accordion-button:not(.collapsed)::after{background-image:var(--bs-accordion-btn-active-icon);transform:var(--bs-accordion-btn-icon-transform)}.accordion-button::after{flex-shrink:0;width:var(--bs-accordion-btn-icon-width);height:var(--bs-accordion-btn-icon-width);margin-left:auto;content:"";background-image:var(--bs-accordion-btn-icon);background-repeat:no-repeat;background-size:var(--bs-accordion-btn-icon-width);transition:var(--bs-accordion-btn-icon-transition)}@media (prefers-reduced-motion:reduce){.accordion-button::after{transition:none}}.accordion-button:hover{z-index:2}.accordion-button:focus{z-index:3;border-color:var(--bs-accordion-btn-focus-border-color);outline:0;box-shadow:var(--bs-accordion-btn-focus-box-shadow)}.accordion-header{margin-bottom:0}.accordion-item{color:var(--bs-accordion-color);background-color:var(--bs-accordion-bg);border:var(--bs-accordion-border-width) solid var(--bs-accordion-border-color)}.accordion-item:first-of-type{border-top-left-radius:var(--bs-accordion-border-radius);border-top-right-radius:var(--bs-accordion-border-radius)}.accordion-item:first-of-type .accordion-button{border-top-left-radius:var(--bs-accordion-inner-border-radius);border-top-right-radius:var(--bs-accordion-inner-border-radius)}.accordion-item:not(:first-of-type){border-top:0}.accordion-item:last-of-type{border-bottom-right-radius:var(--bs-accordion-border-radius);border-bottom-left-radius:var(--bs-accordion-border-radius)}.accordion-item:last-of-type .accordion-button.collapsed{border-bottom-right-radius:var(--bs-accordion-inner-border-radius);border-bottom-left-radius:var(--bs-accordion-inner-border-radius)}.accordion-item:last-of-type .accordion-collapse{border-bottom-right-radius:var(--bs-accordion-border-radius);border-bottom-left-radius:var(--bs-accordion-border-radius)}.accordion-body{padding:var(--bs-accordion-body-padding-y) 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"/")}.breadcrumb-item.active{color:var(--bs-breadcrumb-item-active-color)}.pagination{--bs-pagination-padding-x:0.75rem;--bs-pagination-padding-y:0.375rem;--bs-pagination-font-size:1rem;--bs-pagination-color:var(--bs-link-color);--bs-pagination-bg:#fff;--bs-pagination-border-width:1px;--bs-pagination-border-color:#dee2e6;--bs-pagination-border-radius:0.375rem;--bs-pagination-hover-color:var(--bs-link-hover-color);--bs-pagination-hover-bg:#e9ecef;--bs-pagination-hover-border-color:#dee2e6;--bs-pagination-focus-color:var(--bs-link-hover-color);--bs-pagination-focus-bg:#e9ecef;--bs-pagination-focus-box-shadow:0 0 0 0.25rem rgba(13, 110, 253, 0.25);--bs-pagination-active-color:#fff;--bs-pagination-active-bg:#0d6efd;--bs-pagination-active-border-color:#0d6efd;--bs-pagination-disabled-color:#6c757d;--bs-pagination-disabled-bg:#fff;--bs-pagination-disabled-border-color:#dee2e6;display:flex;padding-left:0;list-style:none}.page-link{position:relative;display:block;padding:var(--bs-pagination-padding-y) var(--bs-pagination-padding-x);font-size:var(--bs-pagination-font-size);color:var(--bs-pagination-color);text-decoration:none;background-color:var(--bs-pagination-bg);border:var(--bs-pagination-border-width) solid var(--bs-pagination-border-color);transition:color .15s ease-in-out,background-color .15s ease-in-out,border-color .15s ease-in-out,box-shadow .15s ease-in-out}@media (prefers-reduced-motion:reduce){.page-link{transition:none}}.page-link:hover{z-index:2;color:var(--bs-pagination-hover-color);background-color:var(--bs-pagination-hover-bg);border-color:var(--bs-pagination-hover-border-color)}.page-link:focus{z-index:3;color:var(--bs-pagination-focus-color);background-color:var(--bs-pagination-focus-bg);outline:0;box-shadow:var(--bs-pagination-focus-box-shadow)}.active>.page-link,.page-link.active{z-index:3;color:var(--bs-pagination-active-color);background-color:var(--bs-pagination-active-bg);border-color:var(--bs-pagination-active-border-color)}.disabled>.page-link,.page-link.disabled{color:var(--bs-pagination-disabled-color);pointer-events:none;background-color:var(--bs-pagination-disabled-bg);border-color:var(--bs-pagination-disabled-border-color)}.page-item:not(:first-child) .page-link{margin-left:-1px}.page-item:first-child .page-link{border-top-left-radius:var(--bs-pagination-border-radius);border-bottom-left-radius:var(--bs-pagination-border-radius)}.page-item:last-child .page-link{border-top-right-radius:var(--bs-pagination-border-radius);border-bottom-right-radius:var(--bs-pagination-border-radius)}.pagination-lg{--bs-pagination-padding-x:1.5rem;--bs-pagination-padding-y:0.75rem;--bs-pagination-font-size:1.25rem;--bs-pagination-border-radius:0.5rem}.pagination-sm{--bs-pagination-padding-x:0.5rem;--bs-pagination-padding-y:0.25rem;--bs-pagination-font-size:0.875rem;--bs-pagination-border-radius:0.25rem}.badge{--bs-badge-padding-x:0.65em;--bs-badge-padding-y:0.35em;--bs-badge-font-size:0.75em;--bs-badge-font-weight:700;--bs-badge-color:#fff;--bs-badge-border-radius:0.375rem;display:inline-block;padding:var(--bs-badge-padding-y) var(--bs-badge-padding-x);font-size:var(--bs-badge-font-size);font-weight:var(--bs-badge-font-weight);line-height:1;color:var(--bs-badge-color);text-align:center;white-space:nowrap;vertical-align:baseline;border-radius:var(--bs-badge-border-radius,0)}.badge:empty{display:none}.btn .badge{position:relative;top:-1px}.alert{--bs-alert-bg:transparent;--bs-alert-padding-x:1rem;--bs-alert-padding-y:1rem;--bs-alert-margin-bottom:1rem;--bs-alert-color:inherit;--bs-alert-border-color:transparent;--bs-alert-border:1px solid var(--bs-alert-border-color);--bs-alert-border-radius:0.375rem;position:relative;padding:var(--bs-alert-padding-y) var(--bs-alert-padding-x);margin-bottom:var(--bs-alert-margin-bottom);color:var(--bs-alert-color);background-color:var(--bs-alert-bg);border:var(--bs-alert-border);border-radius:var(--bs-alert-border-radius,0)}.alert-heading{color:inherit}.alert-link{font-weight:700}.alert-dismissible{padding-right:3rem}.alert-dismissible .btn-close{position:absolute;top:0;right:0;z-index:2;padding:1.25rem 1rem}.alert-primary{--bs-alert-color:#084298;--bs-alert-bg:#cfe2ff;--bs-alert-border-color:#b6d4fe}.alert-primary .alert-link{color:#06357a}.alert-secondary{--bs-alert-color:#41464b;--bs-alert-bg:#e2e3e5;--bs-alert-border-color:#d3d6d8}.alert-secondary .alert-link{color:#34383c}.alert-success{--bs-alert-color:#0f5132;--bs-alert-bg:#d1e7dd;--bs-alert-border-color:#badbcc}.alert-success .alert-link{color:#0c4128}.alert-info{--bs-alert-color:#055160;--bs-alert-bg:#cff4fc;--bs-alert-border-color:#b6effb}.alert-info .alert-link{color:#04414d}.alert-warning{--bs-alert-color:#664d03;--bs-alert-bg:#fff3cd;--bs-alert-border-color:#ffecb5}.alert-warning .alert-link{color:#523e02}.alert-danger{--bs-alert-color:#842029;--bs-alert-bg:#f8d7da;--bs-alert-border-color:#f5c2c7}.alert-danger .alert-link{color:#6a1a21}.alert-light{--bs-alert-color:#636464;--bs-alert-bg:#fefefe;--bs-alert-border-color:#fdfdfe}.alert-light .alert-link{color:#4f5050}.alert-dark{--bs-alert-color:#141619;--bs-alert-bg:#d3d3d4;--bs-alert-border-color:#bcbebf}.alert-dark .alert-link{color:#101214}@-webkit-keyframes progress-bar-stripes{0%{background-position-x:1rem}}@keyframes progress-bar-stripes{0%{background-position-x:1rem}}.progress{--bs-progress-height:1rem;--bs-progress-font-size:0.75rem;--bs-progress-bg:#e9ecef;--bs-progress-border-radius:0.375rem;--bs-progress-box-shadow:inset 0 1px 2px rgba(0, 0, 0, 0.075);--bs-progress-bar-color:#fff;--bs-progress-bar-bg:#0d6efd;--bs-progress-bar-transition:width 0.6s ease;display:flex;height:var(--bs-progress-height);overflow:hidden;font-size:var(--bs-progress-font-size);background-color:var(--bs-progress-bg);border-radius:var(--bs-progress-border-radius)}.progress-bar{display:flex;flex-direction:column;justify-content:center;overflow:hidden;color:var(--bs-progress-bar-color);text-align:center;white-space:nowrap;background-color:var(--bs-progress-bar-bg);transition:var(--bs-progress-bar-transition)}@media (prefers-reduced-motion:reduce){.progress-bar{transition:none}}.progress-bar-striped{background-image:linear-gradient(45deg,rgba(255,255,255,.15) 25%,transparent 25%,transparent 50%,rgba(255,255,255,.15) 50%,rgba(255,255,255,.15) 75%,transparent 75%,transparent);background-size:var(--bs-progress-height) var(--bs-progress-height)}.progress-bar-animated{-webkit-animation:1s linear infinite progress-bar-stripes;animation:1s linear infinite progress-bar-stripes}@media 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this._supportPointerEvents&&("pen"===t.pointerType||"touch"===t.pointerType)}static isSupported(){return"ontouchstart"in document.documentElement||navigator.maxTouchPoints>0}}const Z="next",tt="prev",et="left",it="right",st="slid.bs.carousel",nt="carousel",ot="active",rt={ArrowLeft:it,ArrowRight:et},at={interval:5e3,keyboard:!0,pause:"hover",ride:!1,touch:!0,wrap:!0},lt={interval:"(number|boolean)",keyboard:"boolean",ride:"(boolean|string)",pause:"(string|boolean)",touch:"boolean",wrap:"boolean"};class ct extends R{constructor(t,e){super(t,e),this._interval=null,this._activeElement=null,this._isSliding=!1,this.touchTimeout=null,this._swipeHelper=null,this._indicatorsElement=Y.findOne(".carousel-indicators",this._element),this._addEventListeners(),this._config.ride===nt&&this.cycle()}static get Default(){return at}static get DefaultType(){return lt}static get NAME(){return"carousel"}next(){this._slide(Z)}nextWhenVisible(){!document.hidden&&h(this._element)&&this.next()}prev(){this._slide(tt)}pause(){this._isSliding&&a(this._element),this._clearInterval()}cycle(){this._clearInterval(),this._updateInterval(),this._interval=setInterval((()=>this.nextWhenVisible()),this._config.interval)}_maybeEnableCycle(){this._config.ride&&(this._isSliding?$.one(this._element,st,(()=>this.cycle())):this.cycle())}to(t){const e=this._getItems();if(t>e.length-1||t<0)return;if(this._isSliding)return void $.one(this._element,st,(()=>this.to(t)));const i=this._getItemIndex(this._getActive());if(i===t)return;const s=t>i?Z:tt;this._slide(s,e[t])}dispose(){this._swipeHelper&&this._swipeHelper.dispose(),super.dispose()}_configAfterMerge(t){return t.defaultInterval=t.interval,t}_addEventListeners(){this._config.keyboard&&$.on(this._element,"keydown.bs.carousel",(t=>this._keydown(t))),"hover"===this._config.pause&&($.on(this._element,"mouseenter.bs.carousel",(()=>this.pause())),$.on(this._element,"mouseleave.bs.carousel",(()=>this._maybeEnableCycle()))),this._config.touch&&J.isSupported()&&this._addTouchEventListeners()}_addTouchEventListeners(){for(const t of Y.find(".carousel-item img",this._element))$.on(t,"dragstart.bs.carousel",(t=>t.preventDefault()));const t={leftCallback:()=>this._slide(this._directionToOrder(et)),rightCallback:()=>this._slide(this._directionToOrder(it)),endCallback:()=>{"hover"===this._config.pause&&(this.pause(),this.touchTimeout&&clearTimeout(this.touchTimeout),this.touchTimeout=setTimeout((()=>this._maybeEnableCycle()),500+this._config.interval))}};this._swipeHelper=new J(this._element,t)}_keydown(t){if(/input|textarea/i.test(t.target.tagName))return;const e=rt[t.key];e&&(t.preventDefault(),this._slide(this._directionToOrder(e)))}_getItemIndex(t){return this._getItems().indexOf(t)}_setActiveIndicatorElement(t){if(!this._indicatorsElement)return;const e=Y.findOne(".active",this._indicatorsElement);e.classList.remove(ot),e.removeAttribute("aria-current");const i=Y.findOne(`[data-bs-slide-to="${t}"]`,this._indicatorsElement);i&&(i.classList.add(ot),i.setAttribute("aria-current","true"))}_updateInterval(){const t=this._activeElement||this._getActive();if(!t)return;const e=Number.parseInt(t.getAttribute("data-bs-interval"),10);this._config.interval=e||this._config.defaultInterval}_slide(t,e=null){if(this._isSliding)return;const i=this._getActive(),s=t===Z,n=e||w(this._getItems(),i,s,this._config.wrap);if(n===i)return;const o=this._getItemIndex(n),r=e=>$.trigger(this._element,e,{relatedTarget:n,direction:this._orderToDirection(t),from:this._getItemIndex(i),to:o});if(r("slide.bs.carousel").defaultPrevented)return;if(!i||!n)return;const a=Boolean(this._interval);this.pause(),this._isSliding=!0,this._setActiveIndicatorElement(o),this._activeElement=n;const l=s?"carousel-item-start":"carousel-item-end",c=s?"carousel-item-next":"carousel-item-prev";n.classList.add(c),g(n),i.classList.add(l),n.classList.add(l),this._queueCallback((()=>{n.classList.remove(l,c),n.classList.add(ot),i.classList.remove(ot,c,l),this._isSliding=!1,r(st)}),i,this._isAnimated()),a&&this.cycle()}_isAnimated(){return this._element.classList.contains("slide")}_getActive(){return Y.findOne(".active.carousel-item",this._element)}_getItems(){return Y.find(".carousel-item",this._element)}_clearInterval(){this._interval&&(clearInterval(this._interval),this._interval=null)}_directionToOrder(t){return m()?t===et?tt:Z:t===et?Z:tt}_orderToDirection(t){return m()?t===tt?et:it:t===tt?it:et}static jQueryInterface(t){return this.each((function(){const e=ct.getOrCreateInstance(this,t);if("number"!=typeof t){if("string"==typeof t){if(void 0===e[t]||t.startsWith("_")||"constructor"===t)throw new TypeError(`No method named "${t}"`);e[t]()}}else e.to(t)}))}}$.on(document,"click.bs.carousel.data-api","[data-bs-slide], [data-bs-slide-to]",(function(t){const e=r(this);if(!e||!e.classList.contains(nt))return;t.preventDefault();const i=ct.getOrCreateInstance(e),s=this.getAttribute("data-bs-slide-to");return s?(i.to(s),void i._maybeEnableCycle()):"next"===B.getDataAttribute(this,"slide")?(i.next(),void i._maybeEnableCycle()):(i.prev(),void i._maybeEnableCycle())})),$.on(window,"load.bs.carousel.data-api",(()=>{const t=Y.find('[data-bs-ride="carousel"]');for(const e of t)ct.getOrCreateInstance(e)})),b(ct);const ht="show",dt="collapse",ut="collapsing",_t='[data-bs-toggle="collapse"]',gt={toggle:!0,parent:null},ft={toggle:"boolean",parent:"(null|element)"};class pt extends R{constructor(t,e){super(t,e),this._isTransitioning=!1,this._triggerArray=[];const i=Y.find(_t);for(const t of i){const e=o(t),i=Y.find(e).filter((t=>t===this._element));null!==e&&i.length&&this._triggerArray.push(t)}this._initializeChildren(),this._config.parent||this._addAriaAndCollapsedClass(this._triggerArray,this._isShown()),this._config.toggle&&this.toggle()}static get Default(){return gt}static get DefaultType(){return ft}static get NAME(){return"collapse"}toggle(){this._isShown()?this.hide():this.show()}show(){if(this._isTransitioning||this._isShown())return;let t=[];if(this._config.parent&&(t=this._getFirstLevelChildren(".collapse.show, .collapse.collapsing").filter((t=>t!==this._element)).map((t=>pt.getOrCreateInstance(t,{toggle:!1})))),t.length&&t[0]._isTransitioning)return;if($.trigger(this._element,"show.bs.collapse").defaultPrevented)return;for(const e of t)e.hide();const e=this._getDimension();this._element.classList.remove(dt),this._element.classList.add(ut),this._element.style[e]=0,this._addAriaAndCollapsedClass(this._triggerArray,!0),this._isTransitioning=!0;const i=`scroll${e[0].toUpperCase()+e.slice(1)}`;this._queueCallback((()=>{this._isTransitioning=!1,this._element.classList.remove(ut),this._element.classList.add(dt,ht),this._element.style[e]="",$.trigger(this._element,"shown.bs.collapse")}),this._element,!0),this._element.style[e]=`${this._element[i]}px`}hide(){if(this._isTransitioning||!this._isShown())return;if($.trigger(this._element,"hide.bs.collapse").defaultPrevented)return;const t=this._getDimension();this._element.style[t]=`${this._element.getBoundingClientRect()[t]}px`,g(this._element),this._element.classList.add(ut),this._element.classList.remove(dt,ht);for(const t of this._triggerArray){const e=r(t);e&&!this._isShown(e)&&this._addAriaAndCollapsedClass([t],!1)}this._isTransitioning=!0,this._element.style[t]="",this._queueCallback((()=>{this._isTransitioning=!1,this._element.classList.remove(ut),this._element.classList.add(dt),$.trigger(this._element,"hidden.bs.collapse")}),this._element,!0)}_isShown(t=this._element){return t.classList.contains(ht)}_configAfterMerge(t){return t.toggle=Boolean(t.toggle),t.parent=c(t.parent),t}_getDimension(){return this._element.classList.contains("collapse-horizontal")?"width":"height"}_initializeChildren(){if(!this._config.parent)return;const t=this._getFirstLevelChildren(_t);for(const e of t){const t=r(e);t&&this._addAriaAndCollapsedClass([e],this._isShown(t))}}_getFirstLevelChildren(t){const e=Y.find(":scope .collapse .collapse",this._config.parent);return Y.find(t,this._config.parent).filter((t=>!e.includes(t)))}_addAriaAndCollapsedClass(t,e){if(t.length)for(const i of t)i.classList.toggle("collapsed",!e),i.setAttribute("aria-expanded",e)}static jQueryInterface(t){const e={};return"string"==typeof t&&/show|hide/.test(t)&&(e.toggle=!1),this.each((function(){const i=pt.getOrCreateInstance(this,e);if("string"==typeof t){if(void 0===i[t])throw new TypeError(`No method named "${t}"`);i[t]()}}))}}$.on(document,"click.bs.collapse.data-api",_t,(function(t){("A"===t.target.tagName||t.delegateTarget&&"A"===t.delegateTarget.tagName)&&t.preventDefault();const e=o(this),i=Y.find(e);for(const t of i)pt.getOrCreateInstance(t,{toggle:!1}).toggle()})),b(pt);const mt="dropdown",bt="ArrowUp",vt="ArrowDown",yt="click.bs.dropdown.data-api",wt="keydown.bs.dropdown.data-api",At="show",Tt='[data-bs-toggle="dropdown"]:not(.disabled):not(:disabled)',Et=`${Tt}.show`,Ct=".dropdown-menu",kt=m()?"top-end":"top-start",Lt=m()?"top-start":"top-end",Ot=m()?"bottom-end":"bottom-start",It=m()?"bottom-start":"bottom-end",St=m()?"left-start":"right-start",Dt=m()?"right-start":"left-start",Nt={offset:[0,2],boundary:"clippingParents",reference:"toggle",display:"dynamic",popperConfig:null,autoClose:!0},Pt={offset:"(array|string|function)",boundary:"(string|element)",reference:"(string|element|object)",display:"string",popperConfig:"(null|object|function)",autoClose:"(boolean|string)"};class xt extends R{constructor(t,e){super(t,e),this._popper=null,this._parent=this._element.parentNode,this._menu=Y.findOne(Ct,this._parent),this._inNavbar=this._detectNavbar()}static get Default(){return Nt}static get DefaultType(){return Pt}static get NAME(){return mt}toggle(){return this._isShown()?this.hide():this.show()}show(){if(d(this._element)||this._isShown())return;const t={relatedTarget:this._element};if(!$.trigger(this._element,"show.bs.dropdown",t).defaultPrevented){if(this._createPopper(),"ontouchstart"in document.documentElement&&!this._parent.closest(".navbar-nav"))for(const t of[].concat(...document.body.children))$.on(t,"mouseover",_);this._element.focus(),this._element.setAttribute("aria-expanded",!0),this._menu.classList.add(At),this._element.classList.add(At),$.trigger(this._element,"shown.bs.dropdown",t)}}hide(){if(d(this._element)||!this._isShown())return;const t={relatedTarget:this._element};this._completeHide(t)}dispose(){this._popper&&this._popper.destroy(),super.dispose()}update(){this._inNavbar=this._detectNavbar(),this._popper&&this._popper.update()}_completeHide(t){if(!$.trigger(this._element,"hide.bs.dropdown",t).defaultPrevented){if("ontouchstart"in document.documentElement)for(const t of[].concat(...document.body.children))$.off(t,"mouseover",_);this._popper&&this._popper.destroy(),this._menu.classList.remove(At),this._element.classList.remove(At),this._element.setAttribute("aria-expanded","false"),B.removeDataAttribute(this._menu,"popper"),$.trigger(this._element,"hidden.bs.dropdown",t)}}_getConfig(t){if("object"==typeof(t=super._getConfig(t)).reference&&!l(t.reference)&&"function"!=typeof t.reference.getBoundingClientRect)throw new TypeError(`${mt.toUpperCase()}: Option "reference" provided type "object" without a required "getBoundingClientRect" method.`);return t}_createPopper(){if(void 0===i)throw new TypeError("Bootstrap's dropdowns require Popper (https://popper.js.org)");let t=this._element;"parent"===this._config.reference?t=this._parent:l(this._config.reference)?t=c(this._config.reference):"object"==typeof this._config.reference&&(t=this._config.reference);const e=this._getPopperConfig();this._popper=i.createPopper(t,this._menu,e)}_isShown(){return this._menu.classList.contains(At)}_getPlacement(){const t=this._parent;if(t.classList.contains("dropend"))return St;if(t.classList.contains("dropstart"))return Dt;if(t.classList.contains("dropup-center"))return"top";if(t.classList.contains("dropdown-center"))return"bottom";const e="end"===getComputedStyle(this._menu).getPropertyValue("--bs-position").trim();return t.classList.contains("dropup")?e?Lt:kt:e?It:Ot}_detectNavbar(){return null!==this._element.closest(".navbar")}_getOffset(){const{offset:t}=this._config;return"string"==typeof t?t.split(",").map((t=>Number.parseInt(t,10))):"function"==typeof t?e=>t(e,this._element):t}_getPopperConfig(){const t={placement:this._getPlacement(),modifiers:[{name:"preventOverflow",options:{boundary:this._config.boundary}},{name:"offset",options:{offset:this._getOffset()}}]};return(this._inNavbar||"static"===this._config.display)&&(B.setDataAttribute(this._menu,"popper","static"),t.modifiers=[{name:"applyStyles",enabled:!1}]),{...t,..."function"==typeof this._config.popperConfig?this._config.popperConfig(t):this._config.popperConfig}}_selectMenuItem({key:t,target:e}){const i=Y.find(".dropdown-menu .dropdown-item:not(.disabled):not(:disabled)",this._menu).filter((t=>h(t)));i.length&&w(i,e,t===vt,!i.includes(e)).focus()}static jQueryInterface(t){return this.each((function(){const e=xt.getOrCreateInstance(this,t);if("string"==typeof t){if(void 0===e[t])throw new TypeError(`No method named "${t}"`);e[t]()}}))}static clearMenus(t){if(2===t.button||"keyup"===t.type&&"Tab"!==t.key)return;const e=Y.find(Et);for(const i of e){const e=xt.getInstance(i);if(!e||!1===e._config.autoClose)continue;const s=t.composedPath(),n=s.includes(e._menu);if(s.includes(e._element)||"inside"===e._config.autoClose&&!n||"outside"===e._config.autoClose&&n)continue;if(e._menu.contains(t.target)&&("keyup"===t.type&&"Tab"===t.key||/input|select|option|textarea|form/i.test(t.target.tagName)))continue;const o={relatedTarget:e._element};"click"===t.type&&(o.clickEvent=t),e._completeHide(o)}}static dataApiKeydownHandler(t){const e=/input|textarea/i.test(t.target.tagName),i="Escape"===t.key,s=[bt,vt].includes(t.key);if(!s&&!i)return;if(e&&!i)return;t.preventDefault();const n=Y.findOne(Tt,t.delegateTarget.parentNode),o=xt.getOrCreateInstance(n);if(s)return t.stopPropagation(),o.show(),void o._selectMenuItem(t);o._isShown()&&(t.stopPropagation(),o.hide(),n.focus())}}$.on(document,wt,Tt,xt.dataApiKeydownHandler),$.on(document,wt,Ct,xt.dataApiKeydownHandler),$.on(document,yt,xt.clearMenus),$.on(document,"keyup.bs.dropdown.data-api",xt.clearMenus),$.on(document,yt,Tt,(function(t){t.preventDefault(),xt.getOrCreateInstance(this).toggle()})),b(xt);const Mt=".fixed-top, .fixed-bottom, .is-fixed, .sticky-top",jt=".sticky-top",$t="padding-right",Ft="margin-right";class Ht{constructor(){this._element=document.body}getWidth(){const t=document.documentElement.clientWidth;return Math.abs(window.innerWidth-t)}hide(){const t=this.getWidth();this._disableOverFlow(),this._setElementAttributes(this._element,$t,(e=>e+t)),this._setElementAttributes(Mt,$t,(e=>e+t)),this._setElementAttributes(jt,Ft,(e=>e-t))}reset(){this._resetElementAttributes(this._element,"overflow"),this._resetElementAttributes(this._element,$t),this._resetElementAttributes(Mt,$t),this._resetElementAttributes(jt,Ft)}isOverflowing(){return this.getWidth()>0}_disableOverFlow(){this._saveInitialAttribute(this._element,"overflow"),this._element.style.overflow="hidden"}_setElementAttributes(t,e,i){const s=this.getWidth();this._applyManipulationCallback(t,(t=>{if(t!==this._element&&window.innerWidth>t.clientWidth+s)return;this._saveInitialAttribute(t,e);const n=window.getComputedStyle(t).getPropertyValue(e);t.style.setProperty(e,`${i(Number.parseFloat(n))}px`)}))}_saveInitialAttribute(t,e){const i=t.style.getPropertyValue(e);i&&B.setDataAttribute(t,e,i)}_resetElementAttributes(t,e){this._applyManipulationCallback(t,(t=>{const i=B.getDataAttribute(t,e);null!==i?(B.removeDataAttribute(t,e),t.style.setProperty(e,i)):t.style.removeProperty(e)}))}_applyManipulationCallback(t,e){if(l(t))e(t);else for(const i of Y.find(t,this._element))e(i)}}const zt="show",qt="mousedown.bs.backdrop",Bt={className:"modal-backdrop",isVisible:!0,isAnimated:!1,rootElement:"body",clickCallback:null},Wt={className:"string",isVisible:"boolean",isAnimated:"boolean",rootElement:"(element|string)",clickCallback:"(function|null)"};class Rt extends W{constructor(t){super(),this._config=this._getConfig(t),this._isAppended=!1,this._element=null}static get Default(){return Bt}static get DefaultType(){return Wt}static get NAME(){return"backdrop"}show(t){if(!this._config.isVisible)return void v(t);this._append();const e=this._getElement();this._config.isAnimated&&g(e),e.classList.add(zt),this._emulateAnimation((()=>{v(t)}))}hide(t){this._config.isVisible?(this._getElement().classList.remove(zt),this._emulateAnimation((()=>{this.dispose(),v(t)}))):v(t)}dispose(){this._isAppended&&($.off(this._element,qt),this._element.remove(),this._isAppended=!1)}_getElement(){if(!this._element){const t=document.createElement("div");t.className=this._config.className,this._config.isAnimated&&t.classList.add("fade"),this._element=t}return this._element}_configAfterMerge(t){return t.rootElement=c(t.rootElement),t}_append(){if(this._isAppended)return;const t=this._getElement();this._config.rootElement.append(t),$.on(t,qt,(()=>{v(this._config.clickCallback)})),this._isAppended=!0}_emulateAnimation(t){y(t,this._getElement(),this._config.isAnimated)}}const Vt=".bs.focustrap",Kt="backward",Qt={trapElement:null,autofocus:!0},Xt={trapElement:"element",autofocus:"boolean"};class Yt extends W{constructor(t){super(),this._config=this._getConfig(t),this._isActive=!1,this._lastTabNavDirection=null}static get Default(){return Qt}static get DefaultType(){return Xt}static get NAME(){return"focustrap"}activate(){this._isActive||(this._config.autofocus&&this._config.trapElement.focus(),$.off(document,Vt),$.on(document,"focusin.bs.focustrap",(t=>this._handleFocusin(t))),$.on(document,"keydown.tab.bs.focustrap",(t=>this._handleKeydown(t))),this._isActive=!0)}deactivate(){this._isActive&&(this._isActive=!1,$.off(document,Vt))}_handleFocusin(t){const{trapElement:e}=this._config;if(t.target===document||t.target===e||e.contains(t.target))return;const i=Y.focusableChildren(e);0===i.length?e.focus():this._lastTabNavDirection===Kt?i[i.length-1].focus():i[0].focus()}_handleKeydown(t){"Tab"===t.key&&(this._lastTabNavDirection=t.shiftKey?Kt:"forward")}}const Ut="hidden.bs.modal",Gt="show.bs.modal",Jt="modal-open",Zt="show",te="modal-static",ee={backdrop:!0,keyboard:!0,focus:!0},ie={backdrop:"(boolean|string)",keyboard:"boolean",focus:"boolean"};class se extends R{constructor(t,e){super(t,e),this._dialog=Y.findOne(".modal-dialog",this._element),this._backdrop=this._initializeBackDrop(),this._focustrap=this._initializeFocusTrap(),this._isShown=!1,this._isTransitioning=!1,this._scrollBar=new Ht,this._addEventListeners()}static get Default(){return ee}static get DefaultType(){return ie}static get NAME(){return"modal"}toggle(t){return this._isShown?this.hide():this.show(t)}show(t){this._isShown||this._isTransitioning||$.trigger(this._element,Gt,{relatedTarget:t}).defaultPrevented||(this._isShown=!0,this._isTransitioning=!0,this._scrollBar.hide(),document.body.classList.add(Jt),this._adjustDialog(),this._backdrop.show((()=>this._showElement(t))))}hide(){this._isShown&&!this._isTransitioning&&($.trigger(this._element,"hide.bs.modal").defaultPrevented||(this._isShown=!1,this._isTransitioning=!0,this._focustrap.deactivate(),this._element.classList.remove(Zt),this._queueCallback((()=>this._hideModal()),this._element,this._isAnimated())))}dispose(){for(const t of[window,this._dialog])$.off(t,".bs.modal");this._backdrop.dispose(),this._focustrap.deactivate(),super.dispose()}handleUpdate(){this._adjustDialog()}_initializeBackDrop(){return new Rt({isVisible:Boolean(this._config.backdrop),isAnimated:this._isAnimated()})}_initializeFocusTrap(){return new Yt({trapElement:this._element})}_showElement(t){document.body.contains(this._element)||document.body.append(this._element),this._element.style.display="block",this._element.removeAttribute("aria-hidden"),this._element.setAttribute("aria-modal",!0),this._element.setAttribute("role","dialog"),this._element.scrollTop=0;const e=Y.findOne(".modal-body",this._dialog);e&&(e.scrollTop=0),g(this._element),this._element.classList.add(Zt),this._queueCallback((()=>{this._config.focus&&this._focustrap.activate(),this._isTransitioning=!1,$.trigger(this._element,"shown.bs.modal",{relatedTarget:t})}),this._dialog,this._isAnimated())}_addEventListeners(){$.on(this._element,"keydown.dismiss.bs.modal",(t=>{if("Escape"===t.key)return this._config.keyboard?(t.preventDefault(),void this.hide()):void this._triggerBackdropTransition()})),$.on(window,"resize.bs.modal",(()=>{this._isShown&&!this._isTransitioning&&this._adjustDialog()})),$.on(this._element,"click.dismiss.bs.modal",(t=>{t.target===t.currentTarget&&("static"!==this._config.backdrop?this._config.backdrop&&this.hide():this._triggerBackdropTransition())}))}_hideModal(){this._element.style.display="none",this._element.setAttribute("aria-hidden",!0),this._element.removeAttribute("aria-modal"),this._element.removeAttribute("role"),this._isTransitioning=!1,this._backdrop.hide((()=>{document.body.classList.remove(Jt),this._resetAdjustments(),this._scrollBar.reset(),$.trigger(this._element,Ut)}))}_isAnimated(){return this._element.classList.contains("fade")}_triggerBackdropTransition(){if($.trigger(this._element,"hidePrevented.bs.modal").defaultPrevented)return;const t=this._element.scrollHeight>document.documentElement.clientHeight,e=this._element.style.overflowY;"hidden"===e||this._element.classList.contains(te)||(t||(this._element.style.overflowY="hidden"),this._element.classList.add(te),this._queueCallback((()=>{this._element.classList.remove(te),this._queueCallback((()=>{this._element.style.overflowY=e}),this._dialog)}),this._dialog),this._element.focus())}_adjustDialog(){const t=this._element.scrollHeight>document.documentElement.clientHeight,e=this._scrollBar.getWidth(),i=e>0;if(i&&!t){const t=m()?"paddingLeft":"paddingRight";this._element.style[t]=`${e}px`}if(!i&&t){const t=m()?"paddingRight":"paddingLeft";this._element.style[t]=`${e}px`}}_resetAdjustments(){this._element.style.paddingLeft="",this._element.style.paddingRight=""}static jQueryInterface(t,e){return this.each((function(){const i=se.getOrCreateInstance(this,t);if("string"==typeof t){if(void 0===i[t])throw new TypeError(`No method named 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e=r(this);if(["A","AREA"].includes(this.tagName)&&t.preventDefault(),d(this))return;$.one(e,ce,(()=>{h(this)&&this.focus()}));const i=Y.findOne(ae);i&&i!==e&&ue.getInstance(i).hide(),ue.getOrCreateInstance(e).toggle(this)})),$.on(window,"load.bs.offcanvas.data-api",(()=>{for(const t of Y.find(ae))ue.getOrCreateInstance(t).show()})),$.on(window,"resize.bs.offcanvas",(()=>{for(const t of Y.find("[aria-modal][class*=show][class*=offcanvas-]"))"fixed"!==getComputedStyle(t).position&&ue.getOrCreateInstance(t).hide()})),V(ue),b(ue);const _e=new Set(["background","cite","href","itemtype","longdesc","poster","src","xlink:href"]),ge=/^(?:(?:https?|mailto|ftp|tel|file|sms):|[^#&/:?]*(?:[#/?]|$))/i,fe=/^data:(?:image\/(?:bmp|gif|jpeg|jpg|png|tiff|webp)|video\/(?:mpeg|mp4|ogg|webm)|audio\/(?:mp3|oga|ogg|opus));base64,[\d+/a-z]+=*$/i,pe=(t,e)=>{const i=t.nodeName.toLowerCase();return e.includes(i)?!_e.has(i)||Boolean(ge.test(t.nodeValue)||fe.test(t.nodeValue)):e.filter((t=>t instanceof RegExp)).some((t=>t.test(i)))},me={"*":["class","dir","id","lang","role",/^aria-[\w-]*$/i],a:["target","href","title","rel"],area:[],b:[],br:[],col:[],code:[],div:[],em:[],hr:[],h1:[],h2:[],h3:[],h4:[],h5:[],h6:[],i:[],img:["src","srcset","alt","title","width","height"],li:[],ol:[],p:[],pre:[],s:[],small:[],span:[],sub:[],sup:[],strong:[],u:[],ul:[]},be={extraClass:"",template:"
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i&&e.classList.add(...i.split(" ")),e}_typeCheckConfig(t){super._typeCheckConfig(t),this._checkContent(t.content)}_checkContent(t){for(const[e,i]of Object.entries(t))super._typeCheckConfig({selector:e,entry:i},ye)}_setContent(t,e,i){const s=Y.findOne(i,t);s&&((e=this._resolvePossibleFunction(e))?l(e)?this._putElementInTemplate(c(e),s):this._config.html?s.innerHTML=this._maybeSanitize(e):s.textContent=e:s.remove())}_maybeSanitize(t){return this._config.sanitize?function(t,e,i){if(!t.length)return t;if(i&&"function"==typeof i)return i(t);const s=(new window.DOMParser).parseFromString(t,"text/html"),n=[].concat(...s.body.querySelectorAll("*"));for(const t of n){const i=t.nodeName.toLowerCase();if(!Object.keys(e).includes(i)){t.remove();continue}const s=[].concat(...t.attributes),n=[].concat(e["*"]||[],e[i]||[]);for(const e of s)pe(e,n)||t.removeAttribute(e.nodeName)}return s.body.innerHTML}(t,this._config.allowList,this._config.sanitizeFn):t}_resolvePossibleFunction(t){return"function"==typeof t?t(this):t}_putElementInTemplate(t,e){if(this._config.html)return e.innerHTML="",void e.append(t);e.textContent=t.textContent}}const Ae=new Set(["sanitize","allowList","sanitizeFn"]),Te="fade",Ee="show",Ce=".modal",ke="hide.bs.modal",Le="hover",Oe="focus",Ie={AUTO:"auto",TOP:"top",RIGHT:m()?"left":"right",BOTTOM:"bottom",LEFT:m()?"right":"left"},Se={animation:!0,template:'',trigger:"hover 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get Default(){return Se}static get DefaultType(){return De}static get NAME(){return"tooltip"}enable(){this._isEnabled=!0}disable(){this._isEnabled=!1}toggleEnabled(){this._isEnabled=!this._isEnabled}toggle(t){if(this._isEnabled){if(t){const e=this._initializeOnDelegatedTarget(t);return e._activeTrigger.click=!e._activeTrigger.click,void(e._isWithActiveTrigger()?e._enter():e._leave())}this._isShown()?this._leave():this._enter()}}dispose(){clearTimeout(this._timeout),$.off(this._element.closest(Ce),ke,this._hideModalHandler),this.tip&&this.tip.remove(),this._disposePopper(),super.dispose()}show(){if("none"===this._element.style.display)throw new Error("Please use show on visible elements");if(!this._isWithContent()||!this._isEnabled)return;const t=$.trigger(this._element,this.constructor.eventName("show")),e=(u(this._element)||this._element.ownerDocument.documentElement).contains(this._element);if(t.defaultPrevented||!e)return;const i=this._getTipElement();this._element.setAttribute("aria-describedby",i.getAttribute("id"));const{container:s}=this._config;if(this._element.ownerDocument.documentElement.contains(this.tip)||(s.append(i),$.trigger(this._element,this.constructor.eventName("inserted"))),this._popper?this._popper.update():this._createPopper(i),i.classList.add(Ee),"ontouchstart"in document.documentElement)for(const t of[].concat(...document.body.children))$.on(t,"mouseover",_);this._queueCallback((()=>{const t=this._isHovered;this._isHovered=!1,$.trigger(this._element,this.constructor.eventName("shown")),t&&this._leave()}),this.tip,this._isAnimated())}hide(){if(!this._isShown())return;if($.trigger(this._element,this.constructor.eventName("hide")).defaultPrevented)return;const t=this._getTipElement();if(t.classList.remove(Ee),"ontouchstart"in document.documentElement)for(const t of[].concat(...document.body.children))$.off(t,"mouseover",_);this._activeTrigger.click=!1,this._activeTrigger.focus=!1,this._activeTrigger.hover=!1,this._isHovered=!1,this._queueCallback((()=>{this._isWithActiveTrigger()||(this._isHovered||t.remove(),this._element.removeAttribute("aria-describedby"),$.trigger(this._element,this.constructor.eventName("hidden")),this._disposePopper())}),this.tip,this._isAnimated())}update(){this._popper&&this._popper.update()}_isWithContent(){return Boolean(this._getTitle())}_getTipElement(){return this.tip||(this.tip=this._createTipElement(this._getContentForTemplate())),this.tip}_createTipElement(t){const e=this._getTemplateFactory(t).toHtml();if(!e)return null;e.classList.remove(Te,Ee),e.classList.add(`bs-${this.constructor.NAME}-auto`);const i=(t=>{do{t+=Math.floor(1e6*Math.random())}while(document.getElementById(t));return t})(this.constructor.NAME).toString();return e.setAttribute("id",i),this._isAnimated()&&e.classList.add(Te),e}setContent(t){let e=!1;this.tip&&(e=this._isShown(),this.tip.remove(),this.tip=null),this._disposePopper(),this.tip=this._createTipElement(t),e&&this.show()}_getTemplateFactory(t){return this._templateFactory?this._templateFactory.changeContent(t):this._templateFactory=new we({...this._config,content:t,extraClass:this._resolvePossibleFunction(this._config.customClass)}),this._templateFactory}_getContentForTemplate(){return{".tooltip-inner":this._getTitle()}}_getTitle(){return this._config.title}_initializeOnDelegatedTarget(t){return this.constructor.getOrCreateInstance(t.delegateTarget,this._getDelegateConfig())}_isAnimated(){return this._config.animation||this.tip&&this.tip.classList.contains(Te)}_isShown(){return this.tip&&this.tip.classList.contains(Ee)}_createPopper(t){const e="function"==typeof this._config.placement?this._config.placement.call(this,t,this._element):this._config.placement,s=Ie[e.toUpperCase()];this._popper=i.createPopper(this._element,t,this._getPopperConfig(s))}_getOffset(){const{offset:t}=this._config;return"string"==typeof t?t.split(",").map((t=>Number.parseInt(t,10))):"function"==typeof t?e=>t(e,this._element):t}_resolvePossibleFunction(t){return"function"==typeof t?t.call(this._element):t}_getPopperConfig(t){const e={placement:t,modifiers:[{name:"flip",options:{fallbackPlacements:this._config.fallbackPlacements}},{name:"offset",options:{offset:this._getOffset()}},{name:"preventOverflow",options:{boundary:this._config.boundary}},{name:"arrow",options:{element:`.${this.constructor.NAME}-arrow`}},{name:"preSetPlacement",enabled:!0,phase:"beforeMain",fn:t=>{this._getTipElement().setAttribute("data-popper-placement",t.state.placement)}}]};return{...e,..."function"==typeof this._config.popperConfig?this._config.popperConfig(e):this._config.popperConfig}}_setListeners(){const t=this._config.trigger.split(" ");for(const e of t)if("click"===e)$.on(this._element,this.constructor.eventName("click"),this._config.selector,(t=>this.toggle(t)));else if("manual"!==e){const t=e===Le?this.constructor.eventName("mouseenter"):this.constructor.eventName("focusin"),i=e===Le?this.constructor.eventName("mouseleave"):this.constructor.eventName("focusout");$.on(this._element,t,this._config.selector,(t=>{const e=this._initializeOnDelegatedTarget(t);e._activeTrigger["focusin"===t.type?Oe:Le]=!0,e._enter()})),$.on(this._element,i,this._config.selector,(t=>{const e=this._initializeOnDelegatedTarget(t);e._activeTrigger["focusout"===t.type?Oe:Le]=e._element.contains(t.relatedTarget),e._leave()}))}this._hideModalHandler=()=>{this._element&&this.hide()},$.on(this._element.closest(Ce),ke,this._hideModalHandler),this._config.selector?this._config={...this._config,trigger:"manual",selector:""}:this._fixTitle()}_fixTitle(){const t=this._config.originalTitle;t&&(this._element.getAttribute("aria-label")||this._element.textContent||this._element.setAttribute("aria-label",t),this._element.removeAttribute("title"))}_enter(){this._isShown()||this._isHovered?this._isHovered=!0:(this._isHovered=!0,this._setTimeout((()=>{this._isHovered&&this.show()}),this._config.delay.show))}_leave(){this._isWithActiveTrigger()||(this._isHovered=!1,this._setTimeout((()=>{this._isHovered||this.hide()}),this._config.delay.hide))}_setTimeout(t,e){clearTimeout(this._timeout),this._timeout=setTimeout(t,e)}_isWithActiveTrigger(){return Object.values(this._activeTrigger).includes(!0)}_getConfig(t){const e=B.getDataAttributes(this._element);for(const t of Object.keys(e))Ae.has(t)&&delete e[t];return t={...e,..."object"==typeof t&&t?t:{}},t=this._mergeConfigObj(t),t=this._configAfterMerge(t),this._typeCheckConfig(t),t}_configAfterMerge(t){return t.container=!1===t.container?document.body:c(t.container),"number"==typeof t.delay&&(t.delay={show:t.delay,hide:t.delay}),t.originalTitle=this._element.getAttribute("title")||"",t.title=this._resolvePossibleFunction(t.title)||t.originalTitle,"number"==typeof t.title&&(t.title=t.title.toString()),"number"==typeof t.content&&(t.content=t.content.toString()),t}_getDelegateConfig(){const t={};for(const e in this._config)this.constructor.Default[e]!==this._config[e]&&(t[e]=this._config[e]);return t}_disposePopper(){this._popper&&(this._popper.destroy(),this._popper=null)}static jQueryInterface(t){return this.each((function(){const e=Ne.getOrCreateInstance(this,t);if("string"==typeof 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