# Copyright (c) Meta Platforms, Inc. and affiliates. # This source code is licensed under the MIT license found in the # LICENSE file in the root directory of this source tree. from abc import ABC, abstractmethod from copy import deepcopy from typing import List, Union import numpy as np from biotite.structure import AtomArray ALL_RESIDUE_TYPES = [ "A", "R", "N", "D", "C", "Q", "E", "G", "H", "I", "L", "K", "M", "F", "P", "S", "T", "W", "Y", "V", ] RESIDUE_TYPES_WITHOUT_CYSTEINE = deepcopy(ALL_RESIDUE_TYPES) RESIDUE_TYPES_WITHOUT_CYSTEINE.remove("C") RESIDUE_TYPES_1to3 = { "A": "ALA", "R": "ARG", "N": "ASN", "D": "ASP", "C": "CYS", "Q": "GLN", "E": "GLU", "G": "GLY", "H": "HIS", "I": "ILE", "L": "LEU", "K": "LYS", "M": "MET", "F": "PHE", "P": "PRO", "S": "SER", "T": "THR", "W": "TRP", "Y": "TYR", "V": "VAL", } RESIDUE_TYPES_3to1 = {v: k for k, v in RESIDUE_TYPES_1to3.items()} class SequenceSegmentFactory(ABC): def __init__(self) -> None: pass @abstractmethod def get(self) -> str: pass @abstractmethod def mutate(self) -> None: pass @abstractmethod def num_mutation_candidates(self) -> int: pass class ConstantSequenceSegment(SequenceSegmentFactory): def __init__(self, sequence: str) -> None: super().__init__() self.sequence = sequence def get(self) -> str: return self.sequence def mutate(self) -> None: pass def num_mutation_candidates(self) -> int: return 0 class FixedLengthSequenceSegment(SequenceSegmentFactory): def __init__( self, initial_sequence: Union[str, int], disallow_mutations_to_cysteine=True, ) -> None: super().__init__() self.mutation_residue_types = ( RESIDUE_TYPES_WITHOUT_CYSTEINE if disallow_mutations_to_cysteine else ALL_RESIDUE_TYPES ) self.sequence = ( initial_sequence if type(initial_sequence) == str else random_sequence( length=initial_sequence, corpus=self.mutation_residue_types ) ) def get(self) -> str: return self.sequence def mutate(self) -> None: self.sequence = substitute_one_amino_acid( self.sequence, self.mutation_residue_types ) def num_mutation_candidates(self) -> int: return len(self.sequence) def substitute_one_amino_acid(sequence: str, corpus: List[str]) -> str: sequence = list(sequence) index = np.random.choice(len(sequence)) sequence[index] = np.random.choice(corpus) return "".join(sequence) def random_sequence(length: int, corpus: List[str]) -> str: "Generate a random sequence using amino acids in corpus." return "".join([np.random.choice(corpus) for _ in range(length)]) def sequence_from_atomarray(atoms: AtomArray) -> str: return "".join( [RESIDUE_TYPES_3to1[aa] for aa in atoms[atoms.atom_name == "CA"].res_name] ) class VariableLengthSequenceSegment(SequenceSegmentFactory): def __init__( self, initial_sequence: Union[str, int], disallow_mutations_to_cysteine=True, mutation_operation_probabilities: List[float] = [ 3., # Substitution weight. 1., # Deletion weight. 1., # Insertion weight. ], ) -> None: super().__init__() self.mutation_residue_types = ( RESIDUE_TYPES_WITHOUT_CYSTEINE if disallow_mutations_to_cysteine else ALL_RESIDUE_TYPES ) self.sequence = ( initial_sequence if type(initial_sequence) == str else random_sequence( length=initial_sequence, corpus=self.mutation_residue_types ) ) self.mutation_operation_probabilities = np.array(mutation_operation_probabilities) self.mutation_operation_probabilities /= self.mutation_operation_probabilities.sum() def get(self) -> str: return self.sequence def mutate(self) -> None: mutation_operation = np.random.choice( [ self._mutate_substitution, self._mutate_deletion, self._mutate_insertion, ], p=self.mutation_operation_probabilities, ) mutation_operation() def _mutate_substitution(self) -> str: self.sequence = substitute_one_amino_acid( self.sequence, self.mutation_residue_types ) def _mutate_deletion(self) -> str: self.sequence = delete_one_amino_acid(self.sequence) def _mutate_insertion(self) -> str: self.sequence = insert_one_amino_acid( self.sequence, self.mutation_residue_types ) def num_mutation_candidates(self) -> int: # NOTE(brianhie): This should be `3*len(self.sequence) + 1`, # since there are `len(self.sequence)` substitutions and # deletions, and `len(self.sequence) + 1` insertions. # However, as this is used to weight sequence segments for # mutations when combined into a multi-segment program, we # just weight by `len(self.sequence)` for now. return len(self.sequence) def delete_one_amino_acid(sequence: str) -> str: index = np.random.choice(len(sequence)) return sequence[:index] + sequence[index + 1 :] def insert_one_amino_acid(sequence: str, corpus: List[str]) -> str: n = len(sequence) index = np.random.randint(0, n) if n > 0 else 0 insertion = np.random.choice(corpus) return sequence[:index] + insertion + sequence[index:]