🧬 Codeine

Codeine is a Python library for generating synonymous protein-coding sequences under biological constraints.

Installation & documentation

Codeine is available on PyPI:

pip install codeine

Full documentation: https://codeine.readthedocs.io/.

Quick start

from codeine import CodingSpace

space = CodingSpace('MKTIIALSYIFCLVF')

print(space.n_valid_sequences)
print(space.sample())

Overview

A protein sequence can typically be encoded by an enormous number of synonymous DNA/RNA coding sequences.

For biotechnological applications such as recombinant expression, we typically must choose a coding sequence while respecting one or more practical constraints, for example:

• avoiding restriction enzyme sites,
• avoiding nucleotide homopolymers,
• fixing specific codons,
• mutating relative to a reference sequence.

Identifying valid coding sequences under such constraints quickly becomes challenging, especially for longer protein sequences.

Codeine represents the complete space of valid coding sequences for a given protein and experimental setup. It enables efficient sampling, enumeration and mutation library design while guaranteeing that the generated sequences satisfy user-specified constraints.

Examples

Count valid sequences:

from codeine import CodingSpace

space = CodingSpace('MKTLEFQNGSCPRYKKL')

print(space.n_valid_sequences)

Sample a single valid sequence:

from codeine import CodingSpace

space = CodingSpace('MKTLEFQNGSCPRYKKL')

seq = space.sample()
print(seq)

Sample many:

from codeine import CodingSpace

space = CodingSpace('MKTLEFQNGSCPRYKKL')

for seq in space.sample(n=5):
    print(seq)

Apply restrictions:

from codeine import CodingSpace, RestrictionSite

space = CodingSpace(
    'MKTLEFQNGSCPRYKKL',
    forbidden_motifs=[
        RestrictionSite.EcoRI,
        RestrictionSite.BamHI,
        'CTGCAG',
    ],
    codon_restrictions={
        2: 'AAG',
        16: 'AAG',
    },
    max_homopolymer=4,
)

print(space.n_valid_sequences)
print(space.sample())

Use custom codon weights to change sampling distribution:

from codeine import CodingSpace, CodonWeights

weights = CodonWeights.ecoli()

space = CodingSpace("MKTLEFQNGSCPRYKKL", codon_weights=weights)

seq = space.sample()
print(seq)

Nonstandard translation tables and RNA:

from codeine import CodingSpace, TranslationTable

table = TranslationTable(table_id=2, rna=True)

space = CodingSpace("MKTLEFQNGSCPRYKKL", translation_table=table)

seq = space.sample()
print(seq)

Enumerate all sequences (only recommended for small spaces):

from codeine import CodingSpace

space = CodingSpace('CYIQNCPLG')

for sequence in space:
    print(sequence)

Explore mutants of a chosen reference sequence:

from codeine import CodingSpace

space = CodingSpace('MKTLEFQNGSCPRYKKL')

reference = space.sample()

mutants = space.mutants(
    reference,
    free_positions=range(5, 14),
    min_nts=2,
    max_nts=5,
)

mutant = mutants.sample()
print(mutant)