#!/usr/bin/env python3

import argparse

import logging

import warnings

from Bio import BiopythonWarning

from Bio.Seq import Seq

from Bio.Alphabet import IUPAC

from tale import TALE

from draco import Draco

from codon import CodonUsage

warnings.simplefilter('ignore', BiopythonWarning)

parser = argparse.ArgumentParser(description='Direct Repeat Aware Codon Optimizer')

parser.add_argument('sequence', help='TALE binding sequence (DNA)')

parser.add_argument('--upstream', help='Protein sequence to include upstream of the repeats', default='', type=str)

parser.add_argument('--downstream', help='Protein sequence to include downstream of the repeats', default='', type=str)

parser.add_argument('--avoid', action='append', help='Avoid this fragment in the optimized sequence (can be specified multiple times)', type=str)

parser.add_argument('--prepend', help='Prepend the optimized sequence with this DNA sequence (this fragment won\'t be optimized)', default='', type=str)

parser.add_argument('--append', help='Append this DNA sequence to the optimized sequence (this fragment won\'t be optimized)', default='', type=str)

parser.add_argument('--check-repeats', help='Check the optimized sequence for repeats', default=True, type=bool)

parser.add_argument('--repeat-len', default=20, help='Max allowed length of a repeat', type=int)

parser.add_argument('--check-inv-repeats', help='Check the optimized sequence for inverse repeats', default=True, type=bool)

parser.add_argument('--inv-repeat-len', default=12, help='Max allowed length of an inverted repeat', type=int)

parser.add_argument('--check-stretch', help='Check for base stretches', default=True, type=bool)

parser.add_argument('--stretch-len', default=8, help='Max allowed length of a base stretch', type=int)

parser.add_argument('--check-gc', help='Check GC content', default=True, type=bool)

parser.add_argument('--max-gc', default=65, help='Max allowed GC content', type=int)

parser.add_argument('--gc-window', default=200, help='GC calculation window', type=int)

parser.add_argument('--repeat-attempts', default=100, help='Max attempts to optimize a repeat', type=int)

parser.add_argument('--seq-attempts', default=1000, help='Max attempts to optimize the sequence', type=int)

parser.add_argument('--handicap', default=1, help='Max codon handicap for the optimized sequence', type=int)

parser.add_argument('--progress', help='Show progress indicator', action='store_true')

parser.add_argument('--log', help='Logging level')

parser.add_argument('--debug', help='Enable debug logging')

args = parser.parse_args()

upstream = 'DTGQLVKIAKRGGVTAMEAVHASRNALTGAPLN'

downstream = 'SIVAQLSRPDPALAALTNDHLVALACLGGRPAM'

if args.debug:

args.log = 'DEBUG'

if args.log:

logging.basicConfig(level=args.log.upper())

logging.getLogger('BiopythonWarning').setLevel(logging.INFO)

target = Seq(args.sequence, alphabet=IUPAC.ambiguous_dna)

upstream = Seq(args.upstream, alphabet=IUPAC.protein)

downstream = Seq(args.downstream, alphabet=IUPAC.protein)

tale = TALE(target, upstream=upstream, downstream=downstream)

codons = CodonUsage(CodonUsage.Dmel)

draco = Draco(tale, codons, args.avoid, args.prepend, args.append,

args.check_repeats, args.repeat_len, args.repeat_len,

args.check_inv_repeats, args.inv_repeat_len, args.inv_repeat_len,

args.check_stretch, args.stretch_len,

args.check_gc, args.max_gc, args.gc_window,

args.repeat_attempts, args.seq_attempts,

args.handicap, args.progress)

dna = draco.random()

if dna:

dna = dna.back_transcribe()

print('\n' + str(dna))