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import logging |
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from dataclasses import dataclass |
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from typing import Sequence |
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import re |
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from pocketutils.core.dot_dict import NestedDotDict |
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from mandos.model import ChemblCompound |
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from mandos.model.targets import Target |
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from mandos.search.chembl.protein_search import ProteinHit, ProteinSearch |
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from mandos.search.chembl.target_traversal_strategy import ( |
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TargetTraversalStrategy, |
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TargetTraversalStrategies, |
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) |
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logger = logging.getLogger("mandos") |
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@dataclass(frozen=True, order=True, repr=True) |
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class ActivityHit(ProteinHit): |
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""" |
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An "activity" hit for a compound. |
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""" |
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taxon_id: int |
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taxon_name: str |
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pchembl: float |
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std_type: str |
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src_id: str |
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exact_target_id: str |
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@property |
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def predicate(self) -> str: |
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return "activity" |
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class ActivitySearch(ProteinSearch[ActivityHit]): |
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""" |
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Search for ``activity``. |
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""" |
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@property |
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def default_traversal_strategy(self) -> TargetTraversalStrategy: |
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return TargetTraversalStrategies.strategy0(self.api) |
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def query(self, parent_form: ChemblCompound) -> Sequence[NestedDotDict]: |
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def set_to_regex(values) -> str: |
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return "(" + "|".join([f"(?:{re.escape(v)})" for v in values]) + ")" |
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filters = dict( |
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parent_molecule_chembl_id=parent_form.chid, |
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assay_type__iregex=set_to_regex(self.config.allowed_assay_types), |
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standard_relation__iregex=set_to_regex(self.config.allowed_relations), |
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pchembl_value__isnull=False if self.config.require_pchembl else None, |
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target_organism__isnull=False if self.config.require_taxon else None, |
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) |
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# I'd rather not figure out how the API interprets None, so remove them |
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filters = {k: v for k, v in filters.items() if v is not None} |
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return list(self.api.activity.filter(**filters)) |
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def should_include( |
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self, lookup: str, compound: ChemblCompound, data: NestedDotDict, target: Target |
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) -> bool: |
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if ( |
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data.get_as("data_validity_comment", lambda s: s.lower()) |
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in {s.lower() for s in self.config.banned_flags} |
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or data.req_as("standard_relation", str) not in self.config.allowed_relations |
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or data.req_as("assay_type", str) not in self.config.allowed_assay_types |
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or data.get("target_tax_id") is None |
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and self.config.require_taxon |
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or data.get_as("target_tax_id", int) not in self.tax |
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and self.config.require_taxon |
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or data.get("pchembl_value") is None |
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and self.config.require_pchembl |
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or data.req_as("pchembl_value", float) < self.config.min_pchembl |
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and self.config.require_pchembl |
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): |
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return False |
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if data.get("data_validity_comment") is not None: |
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logger.warning( |
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f"Activity annotation for {lookup} has flag '{data.get('data_validity_comment')} (ok)" |
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) |
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# The `target_organism` doesn't always match the `assay_organism` |
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# Ex: see assay CHEMBL823141 / document CHEMBL1135642 for homo sapiens in xenopus laevis |
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# However, it's often something like yeast expressing a human / mouse / etc receptor |
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# So there's no need to filter by it |
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assay = self.api.assay.get(data.req_as("assay_chembl_id", str)) |
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confidence_score = assay.get("confidence_score") |
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if target.type.name.lower() not in {s.lower() for s in self.config.allowed_target_types}: |
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logger.warning(f"Excluding {target} with type {target.type}") |
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return False |
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if self.config.require_confidence_score: |
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if confidence_score is None or confidence_score < self.config.min_confidence_score: |
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return False |
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# Even if we supposedly allow the target type, it doesn't make sense for some confidence scores |
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# Some of these are non-protein types] |
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# And if it's unknown, we don't know what to do with it |
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if ( |
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target.type.is_unknown |
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or target.type.is_strange |
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and self.config.min_confidence_score > 3 |
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): |
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logger.warning(f"Excluding {target} with type {target.type}") |
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return False |
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return True |
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def to_hit( |
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self, lookup: str, compound: ChemblCompound, data: NestedDotDict, target: Target |
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) -> Sequence[ActivityHit]: |
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# these must match the constructor of the Hit, |
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# EXCEPT for object_id and object_name, which come from traversal |
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x = self._extract(lookup, compound, data) |
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return [ActivityHit(**x, object_id=target.chembl, object_name=target.name)] |
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def _extract(self, lookup: str, compound: ChemblCompound, data: NestedDotDict) -> NestedDotDict: |
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# we know these exist from the query |
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organism = data.req_as("target_organism", str) |
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tax_id = data.req_as("target_tax_id", int) |
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tax = self.tax.req(tax_id) |
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if organism != tax.name: |
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logger.warning(f"Target organism {organism} is not {tax.name}") |
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return NestedDotDict( |
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dict( |
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record_id=data.req_as("activity_id", str), |
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compound_id=compound.chid, |
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inchikey=compound.inchikey, |
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compound_name=compound.name, |
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compound_lookup=lookup, |
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taxon_id=tax.id, |
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taxon_name=tax.name, |
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pchembl=data.req_as("pchembl_value", float), |
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std_type=data.req_as("standard_type", str), |
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src_id=data.req_as("src_id", str), |
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exact_target_id=data.req_as("target_chembl_id", str), |
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) |
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) |
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__all__ = ["ActivityHit", "ActivitySearch"] |
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dmyersturnbull /
mandos
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