import matplotlib.pyplot as plt
import seaborn as sb
import pandas as pd
import os
import random
from cami_suite import cami
import utils.comparison_matrix as comparison_matrix
import numpy as np
from utils import kolmogorov_smirnoff

def predict_and_make_consensus(cami, vis=False):
    result_sets = cami.make_predictions()
    cami.create_consensus(result_sets, save_output=False)
    if vis:
        n_results = len(cami.result_gene_sets)
        cami.visualize_and_save_comparison_matrix()
        if vis:
            cami.use_nvenn(download=True)
            
def make_seedvariation(cami, n_iterations, removal_frac=0.2, vis=False, plot=True):
    identifier = cami.uid
    base_seeds = cami.origin_seed_lst
    original_seeds = [cami.ppi_vertex2gene[seed] for seed in base_seeds]
    print(f'All given seeds:{original_seeds}')
    
    random.seed(50)
    removal_frac = removal_frac
    nof_iterations = int(n_iterations)
    used_tools = list(cami.result_gene_sets.keys())
    prediction_tools = cami.prediction_tools
    nof_seeds = len(base_seeds)
    nof_removals = max([int(nof_seeds * removal_frac), 1])
    
    redisc_seeds_file = f'{cami.output_dir}/00_seedvariation_rediscovered_seeds.tsv'
    result_table_file = f'{cami.output_dir}/00_seedvariation_result_table.tsv'
    n_results = len(cami.result_gene_sets)

    redisc_intersection_matrix = pd.DataFrame([[0 for _ in range(n_results)] for __ in range(n_results)],
                                                columns = list(cami.result_gene_sets.keys()),
                                                index = list(cami.result_gene_sets.keys()),
                                                dtype=int)
    
    with open(redisc_seeds_file, 'w') as redisc_table:
        with open(result_table_file, 'w') as res_table:
            redisc_table.write('id')
            for tool in used_tools:
                redisc_table.write(f'\t{tool}')                    
            redisc_table.write('\n')
            res_table.write('tool\trdr\trdr_std\tsensitivity\tsensitivity_std\tprecision\tprecision_std')
            for tool in prediction_tools:
                res_table.write(f'\t{tool}_rdr_ks_pvalue')
            for tool in prediction_tools:
                res_table.write(f'\t{tool}_msr_ks_pvalue')
            
            with open(os.path.join(cami.tmp_dir, f'{used_tools[0]}_{cami.uid}_relevance_scores.tsv'), 'r') as f:
                for line in f:
                    val_name = line.split('\t')[0]
                    redisc_table.write(f'\t{val_name}')
            res_table.write('\n')
            # result dictionaries of the form {tool:list(value for each iteration)}
            
            tp_rate_dict = {k:list() for k in used_tools}
            redisc_rate_dict = {k:list() for k in used_tools}
            module_size_dict = {k:list() for k in used_tools}
            
            # removed and used seeds per iteration
            all_removed_seeds = list()
            all_used_seeds = list()
            
            all_redisc_seeds = []
            
            for ident in range(nof_iterations):
                redisc_table.write(f'{ident}')
                # update uid
                new_identifier = identifier + f'_{ident}'
                # reset cami
                cami.reset_cami(new_uid=new_identifier)
#               cami.ppi_graph = original_ppi
                
                #remove seeds (again)
                print(f'Removing {nof_removals} seeds from the original seed list...')
                removed_seeds_idx = random.sample(list(range(nof_seeds)), nof_removals)
                removed_seeds = cami.remove_seeds(removed_seeds_idx)
                rem_seeds = [cami.ppi_vertex2gene[seed] for seed in removed_seeds]
                print(f'Removed: {rem_seeds} from the seed list')
                print('Updating tools and repeat CAMI')
                # reinitialize tools
                cami.initialize_all_tools()
                
                # repeat consensus
                if ident%20==0:     
                    predict_and_make_consensus(cami)
                else:
                    predict_and_make_consensus(cami)
                
                used_seeds = [cami.ppi_vertex2gene[seed] for seed in cami.seed_lst]
                
                redisc_seeds_dict = {}
                result_dict = cami.result_gene_sets
                
                for tool in result_dict:
                    nof_predictions = len(result_dict[tool]) + len(used_seeds)
                    redisc_seeds = set(result_dict[tool]).intersection(set(rem_seeds))
                    redisc_prev = len(redisc_seeds)
                    redisc_rate = redisc_prev / nof_removals
                    redisc_rate_dict[tool].append(redisc_rate)
                    redisc_seeds_dict[tool] = redisc_seeds
                    tp_rate = redisc_prev / len(removed_seeds)
                    tp_rate_dict[tool].append(tp_rate)
                    module_size_frac = redisc_prev / nof_predictions
                    assert module_size_frac <= 1
                    module_size_dict[tool].append(module_size_frac)
                    redisc_table.write('\t')
                    for idx,seed in enumerate(redisc_seeds):
                        if idx == 0:
                            redisc_table.write(f'{list(redisc_seeds)[0]}')
                        else:
                            redisc_table.write(f',{seed}') 
                    print(f'{tool} rediscovered {redisc_seeds} after removing {rem_seeds}.')
                all_redisc_seeds.append(redisc_seeds_dict)
                redisc_table.write('\n')
                all_used_seeds.append(used_seeds)
                all_removed_seeds.append(rem_seeds)
                for algo1 in redisc_seeds_dict:
                    for algo2 in redisc_seeds_dict:
                        redisc_intersection_matrix.loc[algo1,algo2] += len(redisc_seeds_dict[algo1].intersection(redisc_seeds_dict[algo2]))

            for tool in redisc_rate_dict:
                res_table.write(f'{tool}\t')
                res_table.write(f'{np.mean(redisc_rate_dict[tool])}\t')
                res_table.write(f'{np.std(redisc_rate_dict[tool])}\t')
                res_table.write(f'{np.mean(tp_rate_dict[tool])}\t')
                res_table.write(f'{np.std(tp_rate_dict[tool])}\t')
                res_table.write(f'{np.mean(module_size_dict[tool])}\t')
                res_table.write(f'{np.std(module_size_dict[tool])}')
                for pred_tool in prediction_tools:
                    p_val = kolmogorov_smirnoff.calculate_ks_p_value(list(redisc_rate_dict[tool]), 
                                                                     list(redisc_rate_dict[pred_tool]))
                    res_table.write(f'\t{p_val}')
                for pred_tool in prediction_tools:
                    p_val = kolmogorov_smirnoff.calculate_ks_p_value(list(module_size_dict[tool]), 
                                                                     list(module_size_dict[pred_tool]))
                    res_table.write(f'\t{p_val}')
                    
                with open(os.path.join(cami.tmp_dir, f'{tool}_{cami.uid}_relevance_scores.tsv)'), 'r') as f:
                    for line in f:
                        rel_score = line.split('\t')[1].strip()
                        res_table.write(f'\t{rel_score}')
                res_table.write('\n')
    
    print(f'Result tables are saved in the following locations:')
    
    fig1,ax1, fig2,ax2 = comparison_matrix.plot_comparison_matrix(redisc_intersection_matrix, n_rows=cami.nof_tools,
                                                                  title=f'number of times algorithms rediscovered the same seeds after removing {nof_removals} seeds')
    fig1.savefig(f'{cami.output_dir}/same_rediscs_{identifier}_comparison_matrix.png')
    fig2.savefig(f'{cami.output_dir}/same_rediscs_{identifier}_comparison_matrix_normalized.png')
    # print(variation_results)
    # print(rediscovery_rates_results)
    tools = [tool for tool in redisc_rate_dict.keys()]
    tool_labels = tools.copy()
    
    for idx,tool in enumerate(tools):
        if '_' in tool:
            # find the index of the second occurrence of the character
            second_occurrence_index = tool.find('_', tool.find('_') + 1)
            if second_occurrence_index > -1:
                # replace the character at that index with the replacement character
                tool_name = tool[:second_occurrence_index] + '\n' + tool[second_occurrence_index + 1:]
                tool_labels[idx] = tool_name        
    if plot:
        #PLOT
        # Create a figure instance
        #print(sys.getrecursionlimit())
        fig1, (ax1, ax5, ax4) = plt.subplots(3, 1, figsize=(20,20))
        fig1.subplots_adjust(left=0.2)
        # Extract Figure and Axes instance

        # Create a plot
        violins1 = ax1.violinplot([redisc_rate_dict[tool] for tool in tools], showmeans=True, showextrema=True)
            
        for violinpart in list(violins1.keys())[2:]:
            violins1[violinpart].set_color('k')
        
        for violin, tool in zip(violins1['bodies'], tools):
            if tool in [tw.name for tw in cami.tool_wrappers]:        
                violin.set_facecolor('saddlebrown')
            elif tool == 'first_neighbors':
                violin.set_facecolor('orange')
            elif tool in ['union', 'intersection']:
                violin.set_facecolor('peachpuff')
            else:
                violin.set_facecolor('red')
            
        # Add title
        ax1.set_title(f'Rediscovery rate after randomly removing {nof_removals} seeds {nof_iterations} times from {identifier} seeds.', wrap=True, fontsize=14)

        ax1.set_xticks(list(range(1,len(tools)+1)))
        ax1.set_xticklabels(tool_labels)
        ax1.tick_params(axis='x', labelsize=11)

        ax1.set_ylabel('Rediscovery rate (<rediscovered seeds>/<removed seeds>)', wrap=True, fontsize=14)

        violins2 = ax4.violinplot([tp_rate_dict[tool] for tool in tools], showmeans=True, showextrema=True)
        for violinpart in list(violins2.keys())[2:]:
            violins2[violinpart].set_color('k')
        for violin, tool in zip(violins2['bodies'], tools):
            if tool in [tw.name for tw in cami.tool_wrappers]:        
                violin.set_facecolor('tan')
            elif tool == 'first_neighbors':
                violin.set_facecolor('peachpuff')
            elif tool in ['union', 'intersection']:
                violin.set_facecolor('orange')
            else:
                violin.set_facecolor('darkorange')
        # Add title
        ax4.set_title(f'True positive rates after randomly removing {nof_removals} seeds {nof_iterations} times from {identifier} seeds.', wrap=True, fontsize=14)

        ax4.set_xticks(list(range(1,len(tools)+1)))
        ax4.set_xticklabels(tool_labels)
        ax4.tick_params(axis='x', labelsize=11)

        ax4.set_ylabel('Sensitivity (TP/TP + FN)', wrap=True, fontsize=14)

        violins3 = ax5.violinplot([module_size_dict[tool] for tool in tools], showmeans=True, showextrema=True)
        # Add title
        for violinpart in list(violins3.keys())[2:]:
            violins3[violinpart].set_color('k')
            
        for violin, tool in zip(violins3['bodies'], tools):
            if tool in [tw.name for tw in cami.tool_wrappers]:        
                violin.set_facecolor('midnightblue')
            elif tool == 'first_neighbors':
                violin.set_facecolor('mediumblue')
            elif tool in ['union', 'intersection']:
                violin.set_facecolor('lightsteelblue')
            else:
                violin.set_facecolor('royalblue')
                
        ax5.set_title(f'Ratio of number of rediscovered seeds and predicted module size after removing {nof_removals} seeds {nof_iterations} times from {identifier} seeds.', wrap=True, fontsize=14)

        ax5.set_xticks(list(range(1,len(tools)+1)))
        ax5.set_xticklabels(tool_labels)

        ax5.set_ylabel('precision (<rediscovered seeds>/<module size>)', fontsize=14)
        ax5.tick_params(axis='x', labelsize=11)
        fig1.tight_layout()
        fig1.savefig(f'{cami.output_dir}/00_{identifier}_seed_variation_result.png', bbox_inches="tight")
        plt.close(fig1)
        print(f'Violin plot saved under: 00_{identifier}_seed_variation_result.png')
    return cami