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import os
import tempfile
import logging
import requests
import pandas as pd
from tqdm import tqdm
from rdkit import Chem
import pooch
from concurrent.futures import ThreadPoolExecutor, as_completed
from lobster.data import upload_to_s3

logging.basicConfig(level=logging.INFO)
logger = logging.getLogger(__name__)

S3_BASE_URI = os.environ["S3_BASE_URI"]
S3_RAW = f"{S3_BASE_URI}/raw"
S3_PROCESSED = f"{S3_BASE_URI}/pre-processed"

MAX_WORKERS = 16  # for threading

MODALITY_MAPPING = {
    "polypeptide(L)": "amino_acid",
    "polynucleotide": "nucleotide",
    "polyribonucleotide": "nucleotide",
    "polynucleotide (RNA)": "nucleotide",
    "polynucleotide (DNA)": "nucleotide",
    "polydeoxyribonucleotide": "nucleotide",
    "polydeoxyribonucleotide/polyribonucleotide hybrid ": "nucleotide",
    "smiles": "smiles",
}

IDENTIFIERS = {
    "protein-peptide": "11033993",
    "protein-rna": "11033983",
    "protein-protein": "11033984",
    "rna-small_molecule": "11033985",
    "protein-small_molecule": "11033996",
    "protein-ion": "11033989",
    "protein-dna": "11033982",
    "small_molecule-small_molecule": "11033997",
}

def upload_raw_datasets_to_s3() -> None:
    for fname, identifier in IDENTIFIERS.items():
        with tempfile.TemporaryDirectory() as tmpdir:
            local_path = pooch.retrieve(
                f"https://dataverse.harvard.edu/api/access/datafile/{identifier}",
                fname=f"{fname}.csv",
                known_hash=None,
                path=tmpdir,
                progressbar=True,
            )
            upload_to_s3(
                s3_uri=f"{S3_RAW}/{fname}.csv",
                local_filepath=local_path,
            )


def _canonicalize_smiles(smiles: str) -> str | None:
    """Canonicalize SMILES string."""
    mol = Chem.MolFromSmiles(smiles)
    return Chem.MolToSmiles(mol, canonical=True) if mol else None


def _fetch_pdb_data(pdb_id: str) -> list[dict]:
    """Fetch molecular data from PDBe API for a given PDB ID."""
    res = requests.get(f"https://www.ebi.ac.uk/pdbe/api/pdb/entry/molecules/{pdb_id}")

    if res.status_code != 200:
        raise Exception(f"Failed to fetch data for {pdb_id}: {res.status_code}")
    
    return res.json().get(pdb_id.lower(), [])


def _fetch_smiles_data(ligand_id: str) -> str | None:
    """Fetch SMILES string for ligand from PDBe."""
    try:
        res = requests.get(f"https://www.ebi.ac.uk/pdbe/api/pdb/compound/summary/{ligand_id.lower()}")
        
        if res.status_code != 200:
            raise Exception(f"Failed to fetch data for {ligand_id}: {res.status_code}")
        
        ligand_data = res.json().get(ligand_id)[0]
        ligand_data = iter(ligand_data["smiles"])
        while True:
            try:
                smiles = next(ligand_data)["name"]
                return _canonicalize_smiles(smiles)
            except StopIteration:
                break
            except Exception:
                continue
    except Exception as e:
        raise Exception(f"Failed to fetch SMILES for {ligand_id}") from e


def _safe_extract(row_id: str, sequence_extractor: callable) -> dict | None:
    """Safely extract sequences and modalities given a row ID and extractor."""
    try:
        sequences, modalities = sequence_extractor(row_id)
    except Exception as e:
        logger.info(f"Error processing {row_id}: {e}")
        return None

    combined = list(zip(sequences, modalities))
    combined.sort(key=lambda x: x[1] != "polypeptide(L)")
    sequences, modalities = zip(*combined) if combined else ([], [])

    sequences = (list(sequences) + [None] * 5)[:5]
    modalities = (list(modalities) + [None] * 5)[:5]

    return {
        "id": row_id,
        **{f"sequence{i + 1}": sequences[i] for i in range(5)},
        **{f"modality{i + 1}": modalities[i] for i in range(5)},
    }


def process_rows(df: pd.DataFrame, sequence_extractor: callable, debug: bool = False) -> pd.DataFrame:
    """
    Process rows in the dataframe to extract sequence and modality information.

    Parameters
    ----------
    df : pd.DataFrame
        Input dataframe with 'id' column.
    sequence_extractor : callable
        Function to extract sequences and modalities given a row id.
    debug : bool, optional
        If True, only processes first 10 rows.

    Returns
    -------
    pd.DataFrame
        Dataframe with sequence and modality columns.
    """
    row_ids = df["id"].tolist()[:10] if debug else df["id"].tolist()
    results = []
    with ThreadPoolExecutor(max_workers=MAX_WORKERS) as executor:
        futures = {executor.submit(_safe_extract, rid, sequence_extractor): rid for rid in row_ids}
        for future in tqdm(as_completed(futures), total=len(futures)):
            result = future.result()
            if result:
                results.append(result)
    return pd.DataFrame(results).replace(MODALITY_MAPPING)



def extract_protein_nucleotide(row_id: str) -> tuple[list[str], list[str]]:
    """Example ID: 3adi_1.pdb_3adi_1_RNA_D&E.pdb"""
    pdb_id = row_id.split("_")[0]
    pdb_data = _fetch_pdb_data(pdb_id)
    sequences, types = (
        zip(*[(m["sequence"], m["molecule_type"]) for m in pdb_data if "sequence" in m]) if pdb_data else ([], [])
    )
    return list(sequences), list(types)


def extract_protein_small_molecule(row_id: str) -> tuple[list[str], list[str]]:
    """Example ID: 4h4e_1.pdb_4h4e_1_10G_D.pdb"""
    parts = row_id.split("_")
    pdb_id, ligand_id = parts[2], parts[4]
    pdb_data = _fetch_pdb_data(pdb_id)
    sequences, types = (
        zip(*[(m["sequence"], m["molecule_type"]) for m in pdb_data if "sequence" in m]) if pdb_data else ([], [])
    )
    ligand = _fetch_smiles_data(ligand_id)
    if ligand:
        sequences += (ligand,)
        types += ("smiles",)
    return list(sequences), list(types)


def extract_interacting_chains(row_id: str) -> tuple[list[str], list[str]]:
    """Example ID: 2uxq_2_A_B"""
    pdb_id, _, chain_a, chain_b = row_id.split("_")
    chains_of_interest = {chain_a, chain_b}
    molecules = _fetch_pdb_data(pdb_id)
    chain_map = {}
    for m in molecules:
        if "sequence" not in m or "in_chains" not in m:
            continue
        for chain in m["in_chains"]:
            if chain in chains_of_interest:
                chain_map[chain] = (m["sequence"], m["molecule_type"])
    sequences, types = [], []
    for chain in [chain_a, chain_b]:
        if chain in chain_map:
            seq, mol_type = chain_map[chain]
            sequences.append(seq)
            types.append(mol_type)
        else:
            sequences.append(None)
            types.append(None)
    return sequences, types


def process_protein_nucleotide(debug: bool = False) -> None:
    df = pd.read_csv(f"{S3_RAW}/protein-dna.csv", sep="\t")
    df_out = process_rows(df, extract_protein_nucleotide, debug=debug)
    df_out = df_out.drop_duplicates().reset_index(drop=True)
    df_out.to_parquet(f"{S3_PROCESSED}/protein-dna.parquet", index=False)

    df = pd.read_csv(f"{S3_RAW}/protein-rna.csv", sep="\t")
    df_out = process_rows(df, extract_protein_nucleotide, debug=debug)
    df_out = df_out.drop_duplicates().reset_index(drop=True)
    df_out.to_parquet(f"{S3_PROCESSED}/protein-rna.parquet", index=False)


def process_protein_protein(debug: bool = False) -> None:
    df = pd.read_csv(f"{S3_RAW}/protein-protein.csv", sep="\t")
    df_out = process_rows(df, extract_interacting_chains, debug=debug)
    df_out = df_out.drop_duplicates().reset_index(drop=True)
    df_out.to_parquet(f"{S3_PROCESSED}/protein-protein.parquet", index=False)


def process_protein_small_molecule(debug: bool = False) -> None:
    df = pd.read_csv(f"{S3_RAW}/protein-small_molecule.csv", sep="\t")
    df_out = process_rows(df, extract_protein_small_molecule, debug=debug)
    df_out = df_out.dropna(how="all", axis=1).drop_duplicates().reset_index(drop=True)
    df_out.to_parquet(f"{S3_PROCESSED}/protein-small_molecule.parquet", index=False)


def process_smiles_smiles() -> None:
    df = pd.read_csv(f"{S3_RAW}/small_molecule-small_molecule.csv")
    df = df["id"].str.split("_", expand=True)
    df.columns = ["id", "sequence1", "num_1", "sequence2", "num_2"]
    df = df[df["sequence1"] != df["sequence2"]][["sequence1", "sequence2"]]
    df.insert(1, "modality1", "smiles")
    df.insert(3, "modality2", "smiles")
    df = df.drop_duplicates().reset_index(drop=True)
    df.to_parquet(f"{S3_PROCESSED}/small_molecule-small_molecule.parquet", index=False)


if __name__ == "__main__":
    upload_raw_datasets_to_s3()
    process_protein_nucleotide(debug=False)
    process_protein_protein(debug=False)
    process_protein_small_molecule(debug=False)
    process_smiles_smiles()