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# -*- coding: utf-8 -*-
"""
Created on Tue Aug 29 10:34:38 2023

@author: DELL
"""


import base64
import numpy as np
import pandas as pd
from rdkit import Chem
from rdkit.Chem import DataStructs, AllChem
from sklearn.metrics.pairwise import cosine_similarity

import matchms.filtering as msfilters
from molmass import Formula
from matchms import calculate_scores
from matchms.similarity import CosineGreedy
from spec2vec import SpectrumDocument
from spec2vec.vector_operations import calc_vector

from core.pycdk import IsotopeFromString, IsotopeSimilarity
from core.pubchem import retrieve_by_formula, retrieve_by_exact_mass
from core.pubchem import retrieve_by_formula_database, retrieve_by_exact_mass_database


def spectrum_processing(s):
    """This is how one would typically design a desired pre- and post-
    processing pipeline."""
    s = msfilters.default_filters(s)
    if ('adduct_type' in s.metadata.keys()) and ('adduct' not in s.metadata.keys()):
        s.set('adduct', s.get('adduct_type'))
    s = msfilters.correct_charge(s)
    s = msfilters.add_parent_mass(s)
    s = msfilters.add_losses(s)
    s = msfilters.normalize_intensities(s)
    s = msfilters.select_by_mz(s, mz_from=0, mz_to=1000)
    return s


def get_formula_mass(formula):
    formula = formula.replace('+','').replace('-','')
    f = Formula(formula)
    return f.isotope.mass


def search_candidates(s, database, ms1_tolerence = 20):
    if 'formula' in s.metadata.keys():
        formula = s.metadata['formula']
        candidate = retrieve_by_formula_database(formula, database)
        return candidate
        if len(candidate) == 0:
            try:
                candidate = retrieve_by_formula(formula)
                return candidate
            except:
                return None
    
    elif 'parent_mass' in s.metadata.keys():
        mass = float(s.metadata['parent_mass'])
        candidate = retrieve_by_exact_mass_database(mass, database, ppm = ms1_tolerence)
        return candidate
        if len(candidate) == 0:
            try:
                candidate = retrieve_by_exact_mass(mass)
                return candidate
            except:
                return None
    else:
        return None


def calc_isotope_score(s, candidate_mol):
    isotope_score = []
    if s.get('isotope_mz') and s.get('isotope_intensity'):
        isotope_mz = base64.b64decode(s.get('isotope_mz').split("'")[1]).decode("ascii").replace('\n', '')
        isotope_intensity = base64.b64decode(s.get('isotope_intensity').split("'")[1]).decode("ascii").replace('\n', '')
        isotope_mz = [float(s) for s in isotope_mz.replace('[', '').replace(']', '').split(' ') if s != '']
        isotope_intensity = [float(s) for s in isotope_intensity.replace('[', '').replace(']', '').split(' ') if s != '']
        isotope_mz = np.array(isotope_mz)

        adduct_mz = isotope_mz[np.argmax(isotope_intensity)] - s.metadata['parent_mass']
        isotope_mz = isotope_mz - adduct_mz
        
        isotope_intensity = np.array(isotope_intensity)
        isotope_intensity = isotope_intensity / max(isotope_intensity)
        isotope_pattern = np.vstack((isotope_mz, isotope_intensity)).T
    else:
        return None      
    for i in range(len(candidate_mol)):
        try:
            formula = AllChem.CalcMolFormula(candidate_mol[i])
            isotope_ref = IsotopeFromString(formula, minI=0.001)
        except:
            isotope_score.append(0)
        isotope_score.append(IsotopeSimilarity(isotope_pattern, isotope_ref, 10))
    return isotope_score


def calc_deepmass_score(s, candidate_mol, reference_mol, query_vector, reference_vector): 
    get_fp = lambda x: AllChem.GetMorganFingerprintAsBitVect(x, radius=2)
    get_sim = lambda x, y: DataStructs.FingerprintSimilarity(x, y)
    get_corr = lambda x, y: cosine_similarity([x], [y])[0][0]

    k, reference_fp = [], []
    for i, m in enumerate(reference_mol):
        try:
            reference_fp.append(get_fp(m))
            k.append(i)
        except:
            pass
    if len(k) != len(reference_mol):
        k = np.array(k)
        reference_mol = np.array(reference_mol)[k]
        reference_vector = np.array(reference_vector)[k,:]
    
    deepmass_score = []
    for i in range(len(candidate_mol)):
        try:
            candidate_fp_i = get_fp(candidate_mol[i])
        except:
            deepmass_score.append(0)
        candidate_vecsim_i = [get_corr(query_vector, reference_vector_) for reference_vector_ in reference_vector]
        candidate_vecsim_i = np.array(candidate_vecsim_i)
        candidate_fpsim_i = [get_sim(candidate_fp_i, reference_fp_) for reference_fp_ in reference_fp]
        candidate_fpsim_i = np.array(candidate_fpsim_i)
        top20 = np.argsort(-np.array(candidate_fpsim_i))[:20]
        candidate_score_i = np.sqrt(np.sum(candidate_vecsim_i[top20] * candidate_fpsim_i[top20]))
        deepmass_score.append(candidate_score_i / 20)
    deepmass_score = np.array(deepmass_score)
    deepmass_score /= np.max(deepmass_score)
    return deepmass_score


def calc_wt_score(s, candidate_mol):
    candidate_mass = [AllChem.CalcExactMolWt(m) for m in candidate_mol]
    diff_mass = np.array([abs(m - float(s.get['parent_mass'])) for m in candidate_mass])
    wt_score = 1 - 50000 * diff_mass / float(s.get['parent_mass'])
    return wt_score


def identify_unknown(s, p, model, references, database):
    candidate = search_candidates(s, database)
    if candidate is None:
        return s
    if len(candidate) == 0:
        return s
    candidate_mol = [Chem.MolFromSmiles(s) for s in candidate['CanonicalSMILES']]
    query_vector = calc_vector(model, SpectrumDocument(s, n_decimals=2))
    
    xq = np.array(query_vector).astype('float32')
    I, D = p.knn_query(xq, 300)

    reference_spectrum = np.array(references)[I[0,:]]
    reference_smile = [s.metadata['smiles'] for s in reference_spectrum]
    reference_mol = [Chem.MolFromSmiles(s) for s in reference_smile]
    reference_vector = np.array(p.get_items(I[0, :]))

    candidate_deepmass_score = calc_deepmass_score(s, candidate_mol, reference_mol, query_vector, reference_vector)
    candidate['DeepMass Score'] = np.round(candidate_deepmass_score, 4)
    
    if s.get('formula') is None:
        candidate_wt_score = calc_wt_score(s, candidate_mol)
        candidate['MolWt Score'] = np.round(candidate_wt_score, 4)
        if s.get('isotope_mz') and s.get('isotope_intensity'):
            candidate_isotopic_score = calc_isotope_score(s, candidate_mol)
            candidate['Isotope Score'] = np.round(candidate_isotopic_score, 4)
            candidate['Consensus Score'] = 0.8*candidate['DeepMass Score'] + 0.1*candidate['Isotope Score'] + 0.1*candidate['MolWt Score']
        else:
            candidate['Consensus Score'] = 0.8*candidate['DeepMass Score'] + 0.2*candidate['MolWt Score']
        candidate = candidate.sort_values('Consensus Score', ignore_index = True, ascending = False)
    else:
        candidate = candidate.sort_values('DeepMass Score', ignore_index = True, ascending = False)
    
    s.set('annotation', candidate)
    s.set('reference', reference_spectrum)
    return s


def match_spectrum(s, precursors, references):
    precursor = s.get('precursor_mz')
    if precursor is None:
        return s
    lb, ub = precursor - 0.05, precursor + 0.05
    li = np.searchsorted(precursors, lb)
    ui = np.searchsorted(precursors, ub)
    if ui <= li:
        return s
    match_scores = calculate_scores(references = references[li:ui], queries = [s], similarity_function = CosineGreedy())
    # print(match_scores.scores)
    match_scores = np.array([s[0].tolist()[0] for s in match_scores.scores])
    w = np.argsort(-match_scores)
    match_scores = match_scores[w]
    reference = np.array(references)[li:ui][w]
    
    annotation, inchikeys = [], []
    for i, r in enumerate(reference):
        mol = Chem.MolFromSmiles(r.get('smiles'))
        score = match_scores[i]
        if mol is None:
            continue
        inchikey = r.get('inchikey')
        if inchikey == '':
            continue
        title = r.get('compound_name')
        smiles = Chem.MolToSmiles(mol)
        try:
            formula = AllChem.CalcMolFormula(mol)
        except:
            formula = ''
        if inchikey not in inchikeys:
            inchikeys.append(inchikey)
            annotation.append([title, formula, smiles, inchikey, score])
    annotation = pd.DataFrame(annotation, columns = ['Title', 'MolecularFormula', 'CanonicalSMILES', 'InChIKey', 'Matching Score'])
    
    if s.get('formula') is not None:
        annotation = annotation[annotation['MolecularFormula'] == s.get('formula')]
        annotation = annotation.reset_index(drop = True)
    s.set('annotation', annotation)
    s.set('reference', reference)
    return s
    


if __name__ == '__main__':

    '''
    import hnswlib
    import pickle
    import pandas as pd
    from matchms.importing import load_from_mgf
    from gensim.models import Word2Vec
    
    model = Word2Vec.load("model/Ms2Vec_allGNPSpositive.hdf5")
    p = hnswlib.Index(space='l2', dim=300) 
    p.load_index('data/references_index_positive_spec2vec.bin')
    with open('data/references_spectrums_positive.pickle', 'rb') as file:
        references = pickle.load(file)
    references = np.array(references)
    precursors = [s.get('precursor_mz') for s in references]
    precursors = np.array(precursors)
    
    spectrums = [s for s in load_from_mgf("D:/DeepMASS2_Data_Processing/Example/CASMI/all_casmi.mgf")]
    s = spectrums[200]
    s = identify_unknown(s, p, model, reference, database)
    '''