demo/P3LIB/formula_picker.py

import pandas as pd
import pickle
from typing import List, Dict, Optional
from copy import copy as cp
import json

class TCMEntity():
    empty_override = True
    desc = ''
    cid = -1
    entity = 'superclass'

    def __init__(self,
                 pref_name: str, desc: str = '',
                 synonyms: Optional[List[str]] = None,
                 **kwargs):
        self.pref_name = pref_name
        self.desc = desc
        self.synonyms = [] if synonyms is None else [x for x in synonyms if str(x).strip() != 'NA']

        self.targets = {"known": dict(), "predicted": dict()}

        self.formulas = []
        self.herbs = []
        self.ingrs = []

        for k, v in kwargs.items():
            self.__dict__[k] = v

    def serialize(self):
        init_dict = dict(
            cid=self.cid,
            targets_known=self.targets['known'],
            targets_pred=self.targets['predicted'],
            pref_name=self.pref_name, desc=self.desc,
            synonyms=cp(self.synonyms),
            entity=self.entity
        )
        link_dict = self._get_link_dict()
        out_dict = {"init": init_dict, "links": link_dict}
        return out_dict

    @classmethod
    def load(cls,
             db: 'TCMDB', ser_dict: dict,
             skip_links = True):
        init_args = ser_dict['init']

        if skip_links:
            init_args.update({"empty_override":True})
        else:
            init_args.update({"empty_override": False})

        new_entity = cls(**init_args)
        if not skip_links:
            links = ser_dict['links']
            new_entity._set_links(db, links)
        return (new_entity)

    def _get_link_dict(self):
        return dict(
            ingrs=[x.cid for x in self.ingrs],
            herbs=[x.pref_name for x in self.herbs],
            formulas=[x.pref_name for x in self.formulas]
        )

    def _set_links(self, db: 'TCMDB', links: dict):
        for ent_type in links:
            self.__dict__[ent_type] = [db.__dict__[ent_type].get(x) for x in links[ent_type]]
            self.__dict__[ent_type] = [x for x in self.__dict__[ent_type] if x is not None]


class Ingredient(TCMEntity):
    entity: str = 'ingredient'

    def __init__(self, cid: int,
                 targets_pred: Optional[Dict] = None,
                 targets_known: Optional[Dict] = None,
                 synonyms: Optional[List[str]] = None,
                 pref_name: str = '', desc: str = '',
                 empty_override: bool = True, **kwargs):

        if not empty_override:
            assert targets_known is not None or targets_pred is not None, \
                f"Cant submit a compound with no targets at all (CID:{cid})"

        super().__init__(pref_name, synonyms, desc, **kwargs)

        self.cid = cid
        self.targets = {
            'known': targets_known if targets_known is not None else {"symbols": [], 'entrez_ids': []},
            'predicted': targets_pred if targets_pred is not None else {"symbols": [], 'entrez_ids': []}
        }


class Herb(TCMEntity):
    entity: str = 'herb'

    def __init__(self, pref_name: str,
                 ingrs: Optional[List[Ingredient]] = None,
                 synonyms: Optional[List[str]] = None,
                 desc: str = '',
                 empty_override: bool = True, **kwargs):

        if ingrs is None:
            ingrs = []

        if not ingrs and not empty_override:
            raise ValueError(f"No ingredients provided for {pref_name}")

        super().__init__(pref_name, synonyms, desc, **kwargs)

        self.ingrs = ingrs

    def is_same(self, other: 'Herb') -> bool:
        if len(self.ingrs) != len(other.ingrs):
            return False
        this_ingrs = set(x.cid for x in self.ingrs)
        other_ingrs = set(x.cid for x in other.ingrs)
        return this_ingrs == other_ingrs


class Formula(TCMEntity):
    entity: str = 'formula'

    def __init__(self, pref_name: str,
                 herbs: Optional[List[Herb]] = None,
                 synonyms: Optional[List[str]] = None,
                 desc: str = '',
                 empty_override: bool = False, **kwargs):

        if herbs is None:
            herbs = []

        if not herbs and not empty_override:
            raise ValueError(f"No herbs provided for {pref_name}")

        super().__init__(pref_name, synonyms, desc, **kwargs)
        self.herbs = herbs

    def is_same(self, other: 'Formula') -> bool:
        if len(self.herbs) != len(other.herbs):
            return False
        this_herbs = set(x.pref_name for x in self.herbs)
        other_herbs = set(x.pref_name for x in other.herbs)
        return this_herbs == other_herbs


class TCMDB:
    hf_repo: str = "f-galkin/batman2"
    hf_subsets: Dict[str, str] = {'formulas': 'batman_formulas',
                                  'herbs': 'batman_herbs',
                                  'ingredients': 'batman_ingredients'}

    def __init__(self, p_batman: str):
        p_batman = p_batman.removesuffix("/") + "/"

        self.batman_files = dict(p_formulas='formula_browse.txt',
                                 p_herbs='herb_browse.txt',
                                 p_pred_by_tg='predicted_browse_by_targets.txt',
                                 p_known_by_tg='known_browse_by_targets.txt',
                                 p_pred_by_ingr='predicted_browse_by_ingredinets.txt',
                                 p_known_by_ingr='known_browse_by_ingredients.txt')

        self.batman_files = {x: p_batman + y for x, y in self.batman_files.items()}

        self.ingrs = None
        self.herbs = None
        self.formulas = None

    @classmethod
    def make_new_db(cls, p_batman: str):
        new_db = cls(p_batman)

        new_db.parse_ingredients()
        new_db.parse_herbs()
        new_db.parse_formulas()

        return (new_db)

    def parse_ingredients(self):

        pred_tgs = pd.read_csv(self.batman_files['p_pred_by_tg'],
                               sep='\t', index_col=None, header=0,
                               na_filter=False)
        known_tgs = pd.read_csv(self.batman_files['p_known_by_tg'],
                                sep='\t', index_col=None, header=0,
                                na_filter=False)
        entrez_to_symb = {int(pred_tgs.loc[x, 'entrez_gene_id']): pred_tgs.loc[x, 'entrez_gene_symbol'] for x in
                          pred_tgs.index}
        # 9927 gene targets
        entrez_to_symb.update({int(known_tgs.loc[x, 'entrez_gene_id']): \
                                   known_tgs.loc[x, 'entrez_gene_symbol'] for x in known_tgs.index})

        known_ingreds = pd.read_csv(self.batman_files['p_known_by_ingr'],
                                    index_col=0, header=0, sep='\t',
                                    na_filter=False)
        # this BATMAN table is badly formatted
        # you cant just read it
        # df_pred = pd.read_csv(p_pred, index_col=0, header=0, sep='\t')
        pred_ingreds = dict()
        with open(self.batman_files['p_pred_by_ingr'], 'r') as f:
            # skip header
            f.readline()
            newline = f.readline()
            while newline != '':
                cid, other_line = newline.split(' ', 1)
                name, entrez_ids = other_line.rsplit(' ', 1)
                entrez_ids = [int(x.split("(")[0]) for x in entrez_ids.split("|") if not x == "\n"]
                pred_ingreds[int(cid)] = {"targets": entrez_ids, 'name': name}
                newline = f.readline()

        all_BATMAN_CIDs = list(set(pred_ingreds.keys()) | set(known_ingreds.index))
        all_BATMAN_CIDs = [int(x) for x in all_BATMAN_CIDs if str(x).strip() != 'NA']

        # get targets for selected cpds
        ingredients = dict()
        for cid in all_BATMAN_CIDs:
            known_name, pred_name, synonyms = None, None, []
            if cid in known_ingreds.index:
                known_name = known_ingreds.loc[cid, 'IUPAC_name']
                known_symbs = known_ingreds.loc[cid, 'known_target_proteins'].split("|")
            else:
                known_symbs = []

            pred_ids = pred_ingreds.get(cid, [])
            if pred_ids:
                pred_name = pred_ids.get('name')
                if known_name is None:
                    cpd_name = pred_name
                elif known_name != pred_name:
                    cpd_name = min([known_name, pred_name], key=lambda x: sum([x.count(y) for y in "'()-[]1234567890"]))
                    synonyms = [x for x in [known_name, pred_name] if x != cpd_name]

                pred_ids = pred_ids.get('targets', [])

            ingredients[cid] = dict(pref_name=cpd_name,
                                    synonyms=synonyms,
                                    targets_known={"symbols": known_symbs,
                                                   "entrez_ids": [int(x) for x, y in entrez_to_symb.items() if
                                                                  y in known_symbs]},
                                    targets_pred={"symbols": [entrez_to_symb.get(x) for x in pred_ids],
                                                  "entrez_ids": pred_ids})
        ingredients_objs = {x: Ingredient(cid=x, **y) for x, y in ingredients.items()}
        self.ingrs = ingredients_objs

    def parse_herbs(self):
        if self.ingrs is None:
            raise ValueError("Herbs cannot be added before the ingredients")
        # load the herbs file
        name_cols = ['Pinyin.Name', 'Chinese.Name', 'English.Name', 'Latin.Name']
        herbs_df = pd.read_csv(self.batman_files['p_herbs'],
                               index_col=None, header=0, sep='\t',
                               na_filter=False)
        for i in herbs_df.index:

            herb_name = herbs_df.loc[i, 'Pinyin.Name'].strip()
            if herb_name == 'NA':
                herb_name = [x.strip() for x in herbs_df.loc[i, name_cols].tolist() if not x == 'NA']
                herb_name = [x for x in herb_name if x != '']
                if not herb_name:
                    raise ValueError(f"LINE {i}: provided a herb with no names")
                else:
                    herb_name = herb_name[-1]

            herb_cids = herbs_df.loc[i, 'Ingredients'].split("|")

            herb_cids = [x.split("(")[-1].removesuffix(")").strip() for x in herb_cids]
            herb_cids = [int(x) for x in herb_cids if x.isnumeric()]

            missed_ingrs = [x for x in herb_cids if self.ingrs.get(x) is None]
            for cid in missed_ingrs:
                self.add_ingredient(cid=int(cid), pref_name='',
                                    empty_override=True)
            herb_ingrs = [self.ingrs[int(x)] for x in herb_cids]

            self.add_herb(pref_name=herb_name,
                          ingrs=herb_ingrs,
                          synonyms=[x for x in herbs_df.loc[i, name_cols].tolist() if not x == "NA"],
                          empty_override=True)

    def parse_formulas(self):
        if self.herbs is None:
            raise ValueError("Formulas cannot be added before the herbs")
        formulas_df = pd.read_csv(self.batman_files['p_formulas'], index_col=None, header=0,
                                  sep='\t', na_filter=False)
        for i in formulas_df.index:

            composition = formulas_df.loc[i, 'Pinyin.composition'].split(",")
            composition = [x.strip() for x in composition if not x.strip() == 'NA']
            if not composition:
                continue

            missed_herbs = [x.strip() for x in composition if self.herbs.get(x) is None]
            for herb in missed_herbs:
                self.add_herb(pref_name=herb,
                              desc='Missing in the original herb catalog, but present among formula components',
                              ingrs=[], empty_override=True)

            formula_herbs = [self.herbs[x] for x in composition]
            self.add_formula(pref_name=formulas_df.loc[i, 'Pinyin.Name'].strip(),
                             synonyms=[formulas_df.loc[i, 'Chinese.Name']],
                             herbs=formula_herbs)

    def add_ingredient(self, **kwargs):
        if self.ingrs is None:
            self.ingrs = dict()

        new_ingr = Ingredient(**kwargs)
        if not new_ingr.cid in self.ingrs:
            self.ingrs.update({new_ingr.cid: new_ingr})

    def add_herb(self, **kwargs):
        if self.herbs is None:
            self.herbs = dict()

        new_herb = Herb(**kwargs)
        old_herb = self.herbs.get(new_herb.pref_name)
        if not old_herb is None:
            if_same = new_herb.is_same(old_herb)
            if if_same:
                return

            same_name = new_herb.pref_name
            all_dupes = [self.herbs[x] for x in self.herbs if x.split('~')[0] == same_name] + [new_herb]
            new_names = [same_name + f"~{x + 1}" for x in range(len(all_dupes))]
            for i, duped in enumerate(all_dupes):
                duped.pref_name = new_names[i]
            self.herbs.pop(same_name)
            self.herbs.update({x.pref_name: x for x in all_dupes})
        else:
            self.herbs.update({new_herb.pref_name: new_herb})

        for cpd in new_herb.ingrs:
            cpd_herbs = [x.pref_name for x in cpd.herbs]
            if not new_herb.pref_name in cpd_herbs:
                cpd.herbs.append(new_herb)

    def add_formula(self, **kwargs):

        if self.formulas is None:
            self.formulas = dict()

        new_formula = Formula(**kwargs)
        old_formula = self.formulas.get(new_formula.pref_name)
        if not old_formula is None:
            is_same = new_formula.is_same(old_formula)
            if is_same:
                return
            same_name = new_formula.pref_name
            all_dupes = [self.formulas[x] for x in self.formulas if x.split('~')[0] == same_name] + [new_formula]
            new_names = [same_name + f"~{x + 1}" for x in range(len(all_dupes))]
            for i, duped in enumerate(all_dupes):
                duped.pref_name = new_names[i]
            self.formulas.pop(same_name)
            self.formulas.update({x.pref_name: x for x in all_dupes})
        else:
            self.formulas.update({new_formula.pref_name: new_formula})

        for herb in new_formula.herbs:
            herb_formulas = [x.pref_name for x in herb.formulas]
            if not new_formula.pref_name in herb_formulas:
                herb.formulas.append(new_formula)

    def link_ingredients_n_formulas(self):
        for h in self.herbs.values():
            for i in h.ingrs:
                fla_names = set(x.pref_name for x in i.formulas)
                i.formulas += [x for x in h.formulas if not x.pref_name in fla_names]
            for f in h.formulas:
                ingr_cids = set(x.cid for x in f.ingrs)
                f.ingrs += [x for x in h.ingrs if not x.cid in ingr_cids]

    def serialize(self):
        out_dict = dict(
            ingredients={cid: ingr.serialize() for cid, ingr in self.ingrs.items()},
            herbs={name: herb.serialize() for name, herb in self.herbs.items()},
            formulas={name: formula.serialize() for name, formula in self.formulas.items()}
        )
        return (out_dict)

    def save_to_flat_json(self, p_out: str):
        ser_db = db.serialize()
        flat_db = dict()
        for ent_type in ser_db:
            for i, obj in ser_db[ent_type].items():
                flat_db[f"{ent_type}:{i}"] = obj
        with open(p_out, "w") as f:
            f.write(json.dumps(flat_db))

    def save_to_json(self, p_out: str):
        with open(p_out, "w") as f:
            json.dump(self.serialize(), f)

    @classmethod
    def load(cls, ser_dict: dict):
        db = cls(p_batman="")

        # make sure to create all entities before you link them together
        db.ingrs = {int(cid): Ingredient.load(db, ingr, skip_links=True) for cid, ingr in
                    ser_dict['ingredients'].items()}
        db.herbs = {name: Herb.load(db, herb, skip_links=True) for name, herb in ser_dict['herbs'].items()}
        db.formulas = {name: Formula.load(db, formula, skip_links=True) for name, formula in
                       ser_dict['formulas'].items()}

        # now set the links
        for i in db.ingrs.values():
            # NB: somehow gotta make it work w/out relying on str-int conversion
            i._set_links(db, ser_dict['ingredients'][str(i.cid)]['links'])
        for h in db.herbs.values():
            h._set_links(db, ser_dict['herbs'][h.pref_name]['links'])
        for f in db.formulas.values():
            f._set_links(db, ser_dict['formulas'][f.pref_name]['links'])
        return (db)

    @classmethod
    def read_from_json(cls, p_file: str):
        with open(p_file, "r") as f:
            json_db = json.load(f)
        db = cls.load(json_db)
        return (db)

    @classmethod
    def download_from_hf(cls):
        from datasets import load_dataset
        dsets = {x: load_dataset(cls.hf_repo, y) for x, y in cls.hf_subsets.items()}

        # speed this up somehow

        known_tgs = {str(x['cid']): [y.split("(") for y in eval(x['targets_known'])] for x in dsets['ingredients']['train']}
        known_tgs = {x:{'symbols':[z[0] for z in y], "entrez_ids":[int(z[1].strip(")")) for z in y]} for x,y in known_tgs.items()}
        pred_tgs = {str(x['cid']): [y.split("(") for y in eval(x['targets_pred'])] for x in dsets['ingredients']['train']}
        pred_tgs = {x:{'symbols':[z[0] for z in y], "entrez_ids":[int(z[1].strip(")")) for z in y]} for x,y in pred_tgs.items()}

        json_db = dict()
        json_db['ingredients'] = {str(x['cid']): {'init': dict(cid=int(x['cid']),
                                                               targets_known=known_tgs[str(x['cid'])],
                                                               targets_pred=pred_tgs[str(x['cid'])],
                                                               pref_name=x['pref_name'],
                                                               synonyms=eval(x['synonyms']),
                                                               desc=x['description']
                                                               ),

                                                  'links': dict(
                                                      herbs=eval(x['herbs']),
                                                      formulas=eval(x['formulas'])
                                                  )
                                                  }
                                  for x in dsets['ingredients']['train']}

        json_db['herbs'] = {x['pref_name']: {'init': dict(pref_name=x['pref_name'],
                                                          synonyms=eval(x['synonyms']),
                                                          desc=x['description']),
                                             'links': dict(ingrs=eval(x['ingredients']),
                                                           formulas=eval(x['formulas']))} for x in
                            dsets['herbs']['train']}

        json_db['formulas'] = {x['pref_name']: {'init': dict(pref_name=x['pref_name'],
                                                             synonyms=eval(x['synonyms']),
                                                             desc=x['description']),
                                                'links': dict(ingrs=eval(x['ingredients']),
                                                              herbs=eval(x['herbs']))} for x in
                               dsets['formulas']['train']}

        db = cls.load(json_db)
        return (db)

    def drop_isolated(self, how='any'):
        match how:
            case 'any':
                self.herbs = {x: y for x, y in self.herbs.items() if (y.ingrs and y.formulas)}
                self.formulas = {x: y for x, y in self.formulas.items() if (y.ingrs and y.herbs)}
                self.ingrs = {x: y for x, y in self.ingrs.items() if (y.formulas and y.herbs)}
            case 'all':
                self.herbs = {x: y for x, y in self.herbs.items() if (y.ingrs or y.formulas)}
                self.formulas = {x: y for x, y in self.formulas.items() if (y.ingrs or y.herbs)}
                self.ingrs = {x: y for x, y in self.ingrs.items() if (y.formulas or y.herbs)}
            case _:
                raise ValueError(f'Unknown how parameter: {how}. Known parameters are "any" and "all"')

    def select_formula_by_cpd(self, cids: List):
        cids = set(x for x in cids if x in self.ingrs)
        if not cids:
            return
        cpd_counts = {x: len(set([z.cid for z in y.ingrs]) & cids) for x, y in self.formulas.items()}
        n_max = max(cpd_counts.values())
        if n_max == 0:
            return (n_max, [])
        selected = [x for x, y in cpd_counts.items() if y == n_max]
        return (n_max, selected)

    def pick_formula_by_cpd(self, cids: List):
        cids = [x for x in cids if x in self.ingrs]
        if not cids:
            return
        raise NotImplementedError()

    def select_formula_by_herb(self, herbs: List):
        raise NotImplementedError()

    def pick_formula_by_herb(self, herbs: List):
        raise NotImplementedError()


def main(ab_initio=False,
         p_BATMAN="./BATMAN/",
         fname='BATMAN_DB.json'):
    p_BATMAN = p_BATMAN.removesuffix("/") + "/"
    # Use in case you want to recreate the TCMDB database of Chinese medicine from BATMAN files
    if ab_initio:
        db = TCMDB.make_new_db(p_BATMAN)
        db.link_ingredients_n_formulas()
        db.save_to_json(p_BATMAN + fname)
        # db.save_to_json('../TCM screening/BATMAN_DB.json')

    else:
        db = TCMDB.read_from_json('../TCM screening/BATMAN_DB.json')
        # db = TCMDB.read_from_json(p_BATMAN + fname)

        cids = [969516,  # curcumin
                445154,  # resveratrol
                5280343,  # quercetin
                6167,  # colchicine
                5280443,  # apigening
                65064,  # EGCG3
                5757,  # estradiol
                5994,  # progesterone
                5280863,  # kaempferol
                107985,  # triptolide
                14985,  # alpha-tocopherol
                1548943,  # Capsaicin
                64982,  # Baicalin
                6013,  # Testosterone
                ]

        p3_formula = db.select_formula_by_cpd(cids)
        # somehow save file if needed ↓
        ser_db = db.serialize()


###

if __name__ == '__main__':
    main(ab_initio=True, p_BATMAN="./BATMAN/", fname='BATMAN_DB.json')