import requests
import tensorflow as tf
import pandas as pd
import numpy as np
from operator import add
from functools import reduce
from keras.models import load_model
import random

# configure GPUs
for gpu in tf.config.list_physical_devices('GPU'):
    tf.config.experimental.set_memory_growth(gpu, enable=True)
if len(tf.config.list_physical_devices('GPU')) > 0:
    tf.config.experimental.set_visible_devices(tf.config.list_physical_devices('GPU')[0], 'GPU')


ntmap = {'A': (1, 0, 0, 0),
         'C': (0, 1, 0, 0),
         'G': (0, 0, 1, 0),
         'T': (0, 0, 0, 1)
         }

def get_seqcode(seq):
    return np.array(reduce(add, map(lambda c: ntmap[c], seq.upper()))).reshape(
        (1, len(seq), -1))

from keras.models import load_model
class DCModelOntar:
    def __init__(self, ontar_model_dir, is_reg=False):
        self.model = load_model(ontar_model_dir)

    def ontar_predict(self, x, channel_first=True):
        if channel_first:
            x = x.transpose([0, 2, 3, 1])
        yp = self.model.predict(x)
        return yp.ravel()


# Function to predict on-target efficiency and format output
def format_prediction_output(gRNAs, model_path):
    dcModel = DCModelOntar(model_path)
    formatted_data = []

    for gRNA in gRNAs:
        # Encode the gRNA sequence
        encoded_seq = get_seqcode(gRNA[0]).reshape(-1,4,1,23)

        # Predict on-target efficiency using the model
        prediction = dcModel.ontar_predict(encoded_seq)

        # Format output
        chr = gRNA[1]
        start = gRNA[2]
        end = gRNA[3]
        strand = gRNA[4]
        formatted_data.append([chr, start, end, strand, gRNA[0], prediction[0]])

    return formatted_data

def fetch_ensembl_transcripts(gene_symbol):
    url = f"https://rest.ensembl.org/lookup/symbol/homo_sapiens/{gene_symbol}?expand=1;content-type=application/json"
    response = requests.get(url)
    if response.status_code == 200:
        gene_data = response.json()
        if 'Transcript' in gene_data:
            return gene_data['Transcript']
        else:
            print("No transcripts found for gene:", gene_symbol)
            return None
    else:
        print(f"Error fetching gene data from Ensembl: {response.text}")
        return None

def fetch_ensembl_sequence(transcript_id):
    url = f"https://rest.ensembl.org/sequence/id/{transcript_id}?content-type=application/json"
    response = requests.get(url)
    if response.status_code == 200:
        sequence_data = response.json()
        if 'seq' in sequence_data:
            return sequence_data['seq']
        else:
            print("No sequence found for transcript:", transcript_id)
            return None
    else:
        print(f"Error fetching sequence data from Ensembl: {response.text}")
        return None

def find_crispr_targets(sequence, chr, start, strand, pam="NGG", target_length=20):
    targets = []
    len_sequence = len(sequence)

    for i in range(len_sequence - len(pam) + 1):
        if sequence[i + 1:i + 3] == pam[1:]:
            if i >= target_length:
                target_seq = sequence[i - target_length:i + 3]
                tar_start = start + i - target_length
                tar_end = start + i + 3
                targets.append([target_seq, chr, tar_start, tar_end, strand])

    return targets

def process_gene(gene_symbol, model_path):
    transcripts = fetch_ensembl_transcripts(gene_symbol)
    all_data = []

    if transcripts:
        for transcript in transcripts:
            transcript_id = transcript['id']
            chr = transcript.get('seq_region_name', 'unknown')
            start = transcript.get('start', 0)
            strand = transcript.get('strand', 'unknown')
            gene_sequence = fetch_ensembl_sequence(transcript_id)

            if gene_sequence:
                gRNA_sites = find_crispr_targets(gene_sequence, chr, start, strand)
                if gRNA_sites:
                    formatted_data = format_prediction_output(gRNA_sites, model_path)
                    all_data.extend(formatted_data)

    return all_data


# Function to save results as CSV
def save_to_csv(data, filename="crispr_results.csv"):
    df = pd.DataFrame(data,
                      columns=["Gene ID", "Start Pos", "End Pos", "Strand", "gRNA", "Prediction"])
    df.to_csv(filename, index=False)