import os
import glob
import tempfile
import subprocess
from pathlib import Path
from typing import Iterable, List, Union, Optional, Dict, Any

import numpy as np
import pandas as pd
import joblib

REPO_ROOT = Path(__file__).resolve().parents[1]
if str(REPO_ROOT) not in __import__("sys").path:
    __import__("sys").path.insert(0, str(REPO_ROOT))
from paths import mafft_path as resolve_mafft

def load_model(path: str):
    try:
        return joblib.load(path)
    except Exception as e:
        raise RuntimeError(
            f"Failed to joblib.load model: {path}\n"
            f"Original error: {repr(e)}\n\n"
            f"Tip: these pickles can be Python/scikit-learn-version sensitive; "
            f"use the same environment used to train/export the models."
        )

@staticmethod
def clean_seq(s: str) -> str:
    s = (s or "").strip().upper().replace(" ", "").replace("\n", "").replace("\r", "")
    if len(s) == 0:
        raise ValueError("Encountered an empty sequence.")
    return s

@staticmethod
def write_fasta(path: str, seqs: List[str]) -> None:
    with open(path, "w", encoding="utf-8") as f:
        for i, seq in enumerate(seqs):
            f.write(f">query_{i}\n")
            f.write(seq + "\n")

@staticmethod
def parse_fasta(path: str) -> pd.DataFrame:
    names, seqs = [], []
    cur_name, cur_seq = None, []
    with open(path, "r", encoding="utf-8") as f:
        for line in f:
            line = line.strip()
            if not line:
                continue
            if line.startswith(">"):
                if cur_name is not None:
                    names.append(cur_name)
                    seqs.append("".join(cur_seq))
                cur_name = line[1:].strip()
                cur_seq = []
            else:
                cur_seq.append(line)
    if cur_name is not None:
        names.append(cur_name)
        seqs.append("".join(cur_seq))

    return pd.DataFrame({"name": names, "seq_align": seqs})


class GFPExcitationPred:
    """
    Predict GFP excitation maximum (ex_model) using the FPredX pipeline:
      1) MAFFT add query fasta to reference alignment (FPredX_mafft.fasta)
      2) One-hot encoding on the *combined* alignment
      3) Keep only features in available_res.csv
      4) Slice last N rows (the added sequences)
      5) Predict with every model in em_model/ and take the mean
    """

    def __init__(
        self,
        root_dir: str = str(REPO_ROOT / "gfp" / "FPredX"),
        laser: float = 488,
        mafft_path: str = None,
        ref_alignment_fasta: str = "FPredX_mafft.fasta",
        available_res_csv: str = "available_res.csv",
        model_dir: str = "ex_model",
        preload_models: bool = True,
    ):
        self.root_dir = os.path.abspath(root_dir)
        self.mafft_path = mafft_path or resolve_mafft()
        self.ref_alignment_fasta = os.path.join(self.root_dir, ref_alignment_fasta)
        self.available_res_csv = os.path.join(self.root_dir, available_res_csv)
        self.model_dir = os.path.join(self.root_dir, model_dir)

        self.laser = laser

        if not os.path.isfile(self.mafft_path):
            raise FileNotFoundError(f"MAFFT not found at: {self.mafft_path}")

        if not os.path.isfile(self.ref_alignment_fasta):
            raise FileNotFoundError(f"Reference alignment fasta not found: {self.ref_alignment_fasta}")

        if not os.path.isfile(self.available_res_csv):
            raise FileNotFoundError(f"available_res.csv not found: {self.available_res_csv}")

        if not os.path.isdir(self.model_dir):
            raise FileNotFoundError(f"Model directory not found: {self.model_dir}")

        self.available_res = pd.read_csv(self.available_res_csv, index_col=0)

        self.model_paths = sorted(glob.glob(os.path.join(self.model_dir, "*")))
        if len(self.model_paths) == 0:
            raise FileNotFoundError(f"No model files found in: {self.model_dir}")

        self._models = None
        if preload_models:
            self._models = [load_model(p) for p in self.model_paths]

    def __call__(self, seqs: Union[str, Iterable[str]]) -> Union[float, np.ndarray]:
        """
        If seqs is a single sequence string -> returns float (predicted emission max).
        If seqs is an iterable of sequences -> returns np.ndarray of floats.
        """
        return self.get_score(seqs)

    def get_score(
        self,
        seqs: Union[str, Iterable[str]],
        return_debug: bool = False,
    ) -> Union[float, np.ndarray, Dict[str, Any]]:
        """
        Predict emission maximum.

        Args:
          seqs: str or iterable[str] of raw (unaligned) amino-acid sequences
          return_debug: if True, returns dict with extra fields (unavailable_list, per_model_preds, etc.)

        Returns:
          float if input is a single sequence, else np.ndarray
          or dict if return_debug=True
        """
        single = isinstance(seqs, str)
        seq_list = [seqs] if single else list(seqs)

        # Basic cleanup
        seq_list = [clean_seq(s) for s in seq_list]
        n = len(seq_list)
        if n == 0:
            raise ValueError("No sequences provided.")

        # Build features via the same MAFFT+onehot pipeline as the script
        X, unavailable_list = self._featurize_with_mafft(seq_list)

        # Predict with all em_model models and average
        per_model = self._predict_all_models(X)  # shape (n_models, n)
        mean_pred = per_model.mean(axis=0)       # shape (n,)

        if return_debug:
            return {
                "mean_pred": mean_pred if not single else float(mean_pred[0]),
                "per_model_pred": per_model,
                "model_paths": self.model_paths,
                "unavailable_list": unavailable_list,
                "n_sequences": n,
                "n_features": X.shape[1],
            }

        return -1 * abs(mean_pred - self.laser)

    def _run_mafft_add(self, query_fasta: str, out_fasta: str) -> None:
        # Equivalent to:
        # mafft --add <query_fasta> --keeplength FPredX_mafft.fasta > out_fasta
        cmd = [
            self.mafft_path,
            "--add",
            query_fasta,
            "--keeplength",
            self.ref_alignment_fasta,
        ]
        with open(out_fasta, "w", encoding="utf-8") as out:
            proc = subprocess.run(cmd, stdout=out, stderr=subprocess.PIPE, text=True)

        if proc.returncode != 0:
            raise RuntimeError(
                "MAFFT failed.\n"
                f"Command: {' '.join(cmd)}\n"
                f"stderr:\n{proc.stderr}"
            )

    def _featurize_with_mafft(self, seqs: List[str]):
        with tempfile.TemporaryDirectory() as td:
            q_fa = os.path.join(td, "query.fasta")
            out_fa = os.path.join(td, "FPredX_mafft_predict.fasta")

            write_fasta(q_fa, seqs)
            self._run_mafft_add(q_fa, out_fa)

            # Read the combined alignment (ref + queries)
            seq_list_df = parse_fasta(out_fa)

            # One-hot on the whole combined alignment (same as script)
            bypos = seq_list_df["seq_align"].apply(lambda x: pd.Series(list(x)))
            one_hot = pd.get_dummies(bypos)

            # Keep only features in available_res.csv (same logic as script)
            one_hot_trim = pd.DataFrame()
            unavailable_list = []
            avail_idx = set(self.available_res.index)

            for col in one_hot.columns:
                if col in avail_idx:
                    one_hot_trim = pd.concat([one_hot_trim, one_hot[col]], axis=1)
                else:
                    unavailable_list.append(col)

            # Take last N rows corresponding to the added sequences (same as script)
            n = len(seqs)
            one_hot_trim = one_hot_trim.iloc[-n:, :].reset_index(drop=True)

            # Model expects numeric matrix
            X = np.asarray(one_hot_trim, dtype=float)
            return X, unavailable_list

    def _predict_all_models(self, X: np.ndarray) -> np.ndarray:
        models = self._models
        if models is None:
            models = [self._load_model(p) for p in self.model_paths]

        preds = []
        for m in models:
            y = m.predict(X)
            y = np.asarray(y).reshape(-1)
            preds.append(y)

        return np.stack(preds, axis=0)


class GFPBrightPred:
    """
    Predict GFP brightness (bright_model) using the FPredX pipeline:
      1) MAFFT add query fasta to reference alignment (FPredX_mafft.fasta)
      2) One-hot encoding on the *combined* alignment
      3) Keep only features in available_res.csv
      4) Slice last N rows (the added sequences)
      5) Predict with every model in em_model/ and take the mean
    """

    def __init__(
        self,
        root_dir: str = str(REPO_ROOT / "gfp" / "FPredX"),
        mafft_path: str = None,
        ref_alignment_fasta: str = "FPredX_mafft.fasta",
        available_res_csv: str = "available_res.csv",
        model_dir: str = "bright_model",
        preload_models: bool = True,
    ):
        self.root_dir = os.path.abspath(root_dir)
        self.mafft_path = mafft_path or resolve_mafft()
        self.ref_alignment_fasta = os.path.join(self.root_dir, ref_alignment_fasta)
        self.available_res_csv = os.path.join(self.root_dir, available_res_csv)
        self.model_dir = os.path.join(self.root_dir, model_dir)

        if not os.path.isfile(self.mafft_path):
            raise FileNotFoundError(f"MAFFT not found at: {self.mafft_path}")

        if not os.path.isfile(self.ref_alignment_fasta):
            raise FileNotFoundError(f"Reference alignment fasta not found: {self.ref_alignment_fasta}")

        if not os.path.isfile(self.available_res_csv):
            raise FileNotFoundError(f"available_res.csv not found: {self.available_res_csv}")

        if not os.path.isdir(self.model_dir):
            raise FileNotFoundError(f"Model directory not found: {self.model_dir}")

        self.available_res = pd.read_csv(self.available_res_csv, index_col=0)

        self.model_paths = sorted(glob.glob(os.path.join(self.model_dir, "*")))
        if len(self.model_paths) == 0:
            raise FileNotFoundError(f"No model files found in: {self.model_dir}")

        self._models = None
        if preload_models:
            self._models = [load_model(p) for p in self.model_paths]

    def __call__(self, seqs: Union[str, Iterable[str]]) -> Union[float, np.ndarray]:
        """
        If seqs is a single sequence string -> returns float (predicted emission max).
        If seqs is an iterable of sequences -> returns np.ndarray of floats.
        """
        return self.get_score(seqs)

    def get_score(
        self,
        seqs: Union[str, Iterable[str]],
        return_debug: bool = False,
    ) -> Union[float, np.ndarray, Dict[str, Any]]:
        """
        Predict emission maximum.

        Args:
          seqs: str or iterable[str] of raw (unaligned) amino-acid sequences
          return_debug: if True, returns dict with extra fields (unavailable_list, per_model_preds, etc.)

        Returns:
          float if input is a single sequence, else np.ndarray
          or dict if return_debug=True
        """
        single = isinstance(seqs, str)
        seq_list = [seqs] if single else list(seqs)

        # Basic cleanup
        seq_list = [clean_seq(s) for s in seq_list]
        n = len(seq_list)
        if n == 0:
            raise ValueError("No sequences provided.")

        # Build features via the same MAFFT+onehot pipeline as the script
        X, unavailable_list = self._featurize_with_mafft(seq_list)

        # Predict with all em_model models and average
        per_model = self._predict_all_models(X)  # shape (n_models, n)
        mean_pred = per_model.mean(axis=0)       # shape (n,)

        if return_debug:
            return {
                "mean_pred": mean_pred if not single else float(mean_pred[0]),
                "per_model_pred": per_model,
                "model_paths": self.model_paths,
                "unavailable_list": unavailable_list,
                "n_sequences": n,
                "n_features": X.shape[1],
            }

        return mean_pred

    def _run_mafft_add(self, query_fasta: str, out_fasta: str) -> None:
        # Equivalent to:
        # mafft --add <query_fasta> --keeplength FPredX_mafft.fasta > out_fasta
        cmd = [
            self.mafft_path,
            "--add",
            query_fasta,
            "--keeplength",
            self.ref_alignment_fasta,
        ]
        with open(out_fasta, "w", encoding="utf-8") as out:
            proc = subprocess.run(cmd, stdout=out, stderr=subprocess.PIPE, text=True)

        if proc.returncode != 0:
            raise RuntimeError(
                "MAFFT failed.\n"
                f"Command: {' '.join(cmd)}\n"
                f"stderr:\n{proc.stderr}"
            )

    def _featurize_with_mafft(self, seqs: List[str]):
        with tempfile.TemporaryDirectory() as td:
            q_fa = os.path.join(td, "query.fasta")
            out_fa = os.path.join(td, "FPredX_mafft_predict.fasta")

            write_fasta(q_fa, seqs)
            self._run_mafft_add(q_fa, out_fa)

            # Read the combined alignment (ref + queries)
            seq_list_df = parse_fasta(out_fa)

            # One-hot on the whole combined alignment (same as script)
            bypos = seq_list_df["seq_align"].apply(lambda x: pd.Series(list(x)))
            one_hot = pd.get_dummies(bypos)

            # Keep only features in available_res.csv (same logic as script)
            one_hot_trim = pd.DataFrame()
            unavailable_list = []
            avail_idx = set(self.available_res.index)

            for col in one_hot.columns:
                if col in avail_idx:
                    one_hot_trim = pd.concat([one_hot_trim, one_hot[col]], axis=1)
                else:
                    unavailable_list.append(col)

            # Take last N rows corresponding to the added sequences (same as script)
            n = len(seqs)
            one_hot_trim = one_hot_trim.iloc[-n:, :].reset_index(drop=True)

            # Model expects numeric matrix
            X = np.asarray(one_hot_trim, dtype=float)
            return X, unavailable_list

    def _predict_all_models(self, X: np.ndarray) -> np.ndarray:
        models = self._models
        if models is None:
            models = [self._load_model(p) for p in self.model_paths]

        preds = []
        for m in models:
            y = m.predict(X)
            y = np.asarray(y).reshape(-1)
            preds.append(y)

        return np.stack(preds, axis=0)


class GFPLength:
    def __init__(self, orig_seq):
        self.orig_seq = orig_seq
        print("Initial Length: ", len(self.orig_seq))

    def __call__(self, seqs):
        return [len(self.orig_seq) - len(seq) for seq in seqs]