code/FLARE/flare/utils/case_study_utils.py

import pandas as pd
from tqdm import tqdm
from rdkit import Chem
import multiprocessing as mp
from tqdm import tqdm
import numpy as np

import sys
import os
parent_dir = os.path.abspath(os.path.join(os.path.dirname(__file__), '..', '..'))
if parent_dir not in sys.path:
    sys.path.insert(0, parent_dir)

database_to_path = {'fdb':"/data/yzhouc01/molecule_data/foodb_2020_04_07_csv/Compound.csv",
                    'hmdb':"/data/yzhouc01/molecule_data/metabolites-2025-09-18.csv",
                    'spectra_db':"/data/yzhouc01/spectra_data/combined_msgym_nist23_multiplex_processed.tsv",
                    'bio_db':"/data/yzhouc01/molecule_data/bio_2023_07_11_smiles.csv",
                    'coconut':"/data/yzhouc01/molecule_data/coconut_csv-05-2025.csv"}

db_to_mass_col = {'fdb':'exact_molecular_weight',
                  'hmdb':'MONO_MASS',
                  'spectra_db':'exact_molecular_weight',
                  'bio_db':'exact_molecular_weight',
                  'coconut':'exact_molecular_weight'}

db_to_smiles_col = {'fdb':'CANONICAL_SMILES',
                    'hmdb':'CANONICAL_SMILES',
                    'spectra_db':'CANONICAL_SMILES',
                    'bio_db':'canonical_smiles',
                    'coconut':'rdkit_canonical_smiles'}


_worker_instance = None


def _init_worker(databases, threshold):
    """Run once per worker process to initialize shared CandidateAssignment."""
    global _worker_instance
    _worker_instance = CandidateAssignment(databases, threshold)


def _worker_retrieve_candidates(parent_mass):
    """Use the global CandidateAssignment instance inside each worker."""
    return _worker_instance.retrieve_candidates(parent_mass)


_worker_instance = None


def _init_worker(databases, threshold):
    """Initialize global CandidateAssignment in each worker (silent)."""
    global _worker_instance
    _worker_instance = CandidateAssignment(databases, threshold, verbose=False)


def _worker_retrieve_candidates(parent_mass):
    """Retrieve candidates using the worker's global CandidateAssignment."""
    return _worker_instance.retrieve_candidates(parent_mass)


class CandidateAssignment:
    def __init__(self, databases=None, threshold=0.01, verbose=True):
        self.threshold = threshold
        self.databases = []
        self.verbose = verbose

        for db in databases:
            if db not in database_to_path:
                raise ValueError(
                    f"Database {db} not recognized. Available: {list(database_to_path.keys())}"
                )
            if not os.path.exists(database_to_path[db]):
                raise ValueError(f"Database file for {db} not found at {database_to_path[db]}")
            self.databases.append(db)

        # Only print in main process
        if self.verbose and mp.current_process().name == "MainProcess":
            print(f"[{os.getpid()}] Loading databases: {self.databases}")

        self.db_dfs = {}
        self._load_databases()

    def _load_databases(self):
        for db in self.databases:
            path = database_to_path[db]
            if path.endswith("tsv"):
                df = pd.read_csv(path, sep="\t", low_memory=False)
            elif path.endswith("csv"):
                df = pd.read_csv(path, low_memory=False)
            else:
                if self.verbose and mp.current_process().name == "MainProcess":
                    print(f"Unable to load database: {db}")
                continue

            # make sure required columns exist
            required_cols = [db_to_mass_col[db], db_to_smiles_col[db]]
            for col in required_cols:
                if col not in df.columns:
                    raise ValueError(f"Column {col} not found in database {db}. {db} columns: {df.columns.tolist()}")

            # convert to proper types
            df[db_to_mass_col[db]] = pd.to_numeric(df[db_to_mass_col[db]], errors='coerce')

            self.db_dfs[db] = df

            # Only print in main process
            if self.verbose and mp.current_process().name == "MainProcess":
                print(f"[{os.getpid()}] Loaded {db} with {len(df)} entries.")

    def retrieve_candidates(self, parent_mass):
        """Retrieve SMILES candidates for a single parent mass."""
        ub = parent_mass + self.threshold
        lb = parent_mass - self.threshold

        smiles_list = []
        for db_name, df in self.db_dfs.items():
            select_rows = df[
                (df[db_to_mass_col[db_name]] >= lb)
                & (df[db_to_mass_col[db_name]] <= ub)
            ]
            smiles_list.extend(select_rows[db_to_smiles_col[db_name]].tolist())

        smiles_list = list(set(smiles_list))
        return parent_mass, smiles_list

    def retrieve_candidates_batch(self, parent_masses, n_workers=25, chunksize=10):
        """Parallel batch retrieval with silent workers."""
        with mp.Pool(
            processes=n_workers,
            initializer=_init_worker,
            initargs=(self.databases, self.threshold),
        ) as pool:
            results = list(
                tqdm(
                    pool.imap(_worker_retrieve_candidates, parent_masses, chunksize=chunksize),
                    total=len(parent_masses),
                    desc="Retrieving candidates",
                )
            )
        return {r[0]: r[1] for r in results}

# P_TBL = Chem.GetPeriodicTable()
# ELECTRON_MASS = 0.00054858
# VALID_ELEMENTS = [
#     "C",
#     "H",
#     "As",
#     "B",
#     "Br",
#     "Cl",
#     "Co",
#     "F",
#     "Fe",
#     "I",
#     "K",
#     "N",
#     "Na",
#     "O",
#     "P",
#     "S",
#     "Se",
#     "Si",
# ]
# VALID_MONO_MASSES = np.array(
#     [P_TBL.GetMostCommonIsotopeMass(i) for i in VALID_ELEMENTS]
# )
# CHEM_MASSES = VALID_MONO_MASSES[:, None]
# ELEMENT_TO_MASS = dict(zip(VALID_ELEMENTS, CHEM_MASSES.squeeze()))

# adduct_to_mass = {
#     "[M+H]+": ELEMENT_TO_MASS["H"] - ELECTRON_MASS,
#     "[M+Na]+": ELEMENT_TO_MASS["Na"] - ELECTRON_MASS,
#     "[M+K]+": ELEMENT_TO_MASS["K"] - ELECTRON_MASS,
#     "[M-H2O+H]+": -ELEMENT_TO_MASS["O"] - ELEMENT_TO_MASS["H"] - ELECTRON_MASS,
#     "[M+H3N+H]+": ELEMENT_TO_MASS["N"] + ELEMENT_TO_MASS["H"] * 4 - ELECTRON_MASS,
#     "[M]+": 0 - ELECTRON_MASS,
#     "[M-H4O2+H]+": -ELEMENT_TO_MASS["O"] * 2 - ELEMENT_TO_MASS["H"] * 3 - ELECTRON_MASS,
#     "[M-H]-": ELEMENT_TO_MASS["H"] + ELECTRON_MASS,
#     "[M+H2O+H]+":ELEMENT_TO_MASS["O"] * 2 + ELEMENT_TO_MASS["H"] * 2 - ELECTRON_MASS,
# }


# def calculate_parent_mass(precursor_mz, adduct):
#     if adduct not in adduct_to_mass:
#         print(f'{adduct} not supported, returning original precursor_mz')
#     return precursor_mz + adduct_to_mass[adduct]


if __name__ == "__main__":
    # get_mol_mass_for_combined()
    ca = CandidateAssignment(databases=['hmdb'])
    candidates = ca.retrieve_candidates(parent_mass=180.0634, threshold=0.01)
    print(candidates)