def main():
domain_length = 15
# energy_constraint = dc.NearestNeighborEnergyConstraint(low_energy=-9.2, high_energy=-7)
numpy_constraints = [ # energy_constraint,
nc.RunsOfBasesConstraint(['C', 'G'], 4),
nc.RunsOfBasesConstraint(['A', 'T'], 4)
]
domain_pool = nc.DomainPool(f'length-{domain_length} domains', domain_length,
numpy_constraints=numpy_constraints, replace_with_close_sequences=True)
random_seed = 0
strands = [nc.Strand([f'{i}' for i in range(1, 50)])]
for strand in strands:
for domain in strand.domains:
domain.pool = domain_pool
params = ns.SearchParameters(
constraints=[nc.nupack_strand_complex_free_energy_constraint(
threshold=-1.5, temperature=52, short_description='StrandSS', parallel=False)],
out_directory='output/hamming_dist_test',
# weigh_violations_equally=True
report_only_violations=False,
random_seed=random_seed,
max_iterations=None)
params.force_overwrite = True # directly deletes output folder contents w/o user input
# params.report_delay = 0.0
design = nc.Design(strands)
ns.search_for_dna_sequences(design, params)
def main() -> None:
args: CLArgs = parse_command_line_arguments()
design = create_design(width=args.width, height=args.height)
thresholds = Thresholds()
constraints = create_constraints(design, thresholds)
params = ns.SearchParameters(
constraints=constraints,
out_directory=args.directory,
restart=args.restart,
random_seed=args.seed,
log_time=True,
)
ns.search_for_dna_sequences(design, params)
def main() -> None:
seesaw_gates = [
*and_or_gate(
integrating_gate_name=10, amplifying_gate_name=1, inputs=[21, 27]),
*and_or_gate(
integrating_gate_name=53, amplifying_gate_name=5, inputs=[18, 22]),
reporter_gate(gate_name=6, input_=5),
*and_or_gate(
integrating_gate_name=20, amplifying_gate_name=8, inputs=[35, 38]),
*and_or_gate(integrating_gate_name=26,
amplifying_gate_name=13,
inputs=[33, 37]),
*and_or_gate(integrating_gate_name=34,
amplifying_gate_name=18,
inputs=[28, 33, 37]),
*and_or_gate(integrating_gate_name=36,
amplifying_gate_name=21,
inputs=[29, 35, 38]),
reporter_gate(gate_name=23, input_=1),
reporter_gate(gate_name=24, input_=13),
reporter_gate(gate_name=25, input_=8),
*and_or_gate(integrating_gate_name=39,
amplifying_gate_name=22,
inputs=[29, 31]),
*and_or_gate(integrating_gate_name=40,
amplifying_gate_name=27,
inputs=[30, 28]),
*and_or_gate(integrating_gate_name=41,
amplifying_gate_name=28,
inputs=[46, 48]),
*and_or_gate(integrating_gate_name=42,
amplifying_gate_name=29,
inputs=[45, 47]),
*and_or_gate(integrating_gate_name=43,
amplifying_gate_name=30,
inputs=[33, 38]),
*and_or_gate(integrating_gate_name=44,
amplifying_gate_name=31,
inputs=[35, 37]),
input_gate(gate_name=33, input_=49),
input_gate(gate_name=35, input_=50),
input_gate(gate_name=37, input_=51),
input_gate(gate_name=38, input_=52),
]
seesaw_circuit = SeesawCircuit(seesaw_gates=seesaw_gates)
strands = seesaw_circuit.strands
non_fuel_strands = []
for s in strands:
if FUEL_DOMAIN not in s.domains:
non_fuel_strands.append(s)
# Uncomment below for debugging:
# for s in sorted(strands, key=lambda s: s.name):
# print(s)
# for c in seesaw_circuit.constraints:
# print(c)
# exit(0)
constraints: List[nc.Constraint] = [
base_difference_constraint(recognition_domains),
strand_substring_constraint(non_fuel_strands, ILLEGAL_SUBSTRINGS)
]
constraints.extend(seesaw_circuit.constraints
) # make mypy happy about the generics with List
design = nc.Design(strands=strands)
params = ns.SearchParameters(
constraints=constraints,
out_directory='output/square_root_circuit',
# weigh_violations_equally=True,
# restart=True
)
ns.search_for_dna_sequences(design, params)
def main() -> None:
args: CLArgs = parse_command_line_arguments()
# domain lengths
# 9: =========
# 10: ==========
# 11: ===========
# 12: ============
#
# /=========--============>
# | n3* e3*
# | strand 2
# | e1* n2*
# \===========--==========]
# /==========--===========>/==========--===========>
# | n1 e1 | n2 e2
# | strand 0 | strand 1
# | w1 s1 | w2 s2
# \============--=========]\============--=========]
# /=========--============>
# | s1* w2*
# | strand 3
# | w4* s4*
# \===========--==========]
initial_design = nc.Design()
strand0: nc.Strand[str] = initial_design.add_strand(
['s1', 'w1', 'n1', 'e1'], name='strand 0')
strand1: nc.Strand[str] = initial_design.add_strand(
['s2', 'w2', 'n2', 'e2'], name='strand 1')
strand2: nc.Strand[None] = initial_design.add_strand(
['n2*', 'e1*', 'n3*', 'e3*'], name='strand 2')
strand3: nc.Strand[str] = initial_design.add_strand(
['s4*', 'w4*', 's1*', 'w2*'], name='strand 3')
if args.initial_design_filename is not None:
with open(args.initial_design_filename, 'r') as file:
design_json_str: str = file.read()
design = nc.Design.from_json(design_json_str)
else:
design = initial_design
numpy_constraints = [
nc.NearestNeighborEnergyConstraint(-9.5, -9.0, 52.0),
nc.BaseCountConstraint(base='G', high_count=1),
nc.RunsOfBasesConstraint(['C', 'G'], 4),
nc.RunsOfBasesConstraint(['A', 'T'], 4),
]
lengths = [9, 10, 11, 12]
domain_pools = {
length: nc.DomainPool(f'length-{length} domains',
length,
numpy_constraints=numpy_constraints)
for length in lengths
}
for strand in [strand0, strand1]:
strand.domains[0].pool = domain_pools[lengths[0]]
strand.domains[1].pool = domain_pools[lengths[3]]
strand.domains[2].pool = domain_pools[lengths[1]]
strand.domains[3].pool = domain_pools[lengths[2]]
strand2.domains[2].pool = domain_pools[lengths[0]]
strand2.domains[3].pool = domain_pools[lengths[3]]
strand3.domains[0].pool = domain_pools[lengths[1]]
strand3.domains[1].pool = domain_pools[lengths[2]]
strand_pairs_no_comp_constraint = nc.rna_duplex_strand_pairs_constraint(
threshold=-1.0,
temperature=52,
short_description='StrandPairNoCompl',
pairs=((strand0, strand1), (strand2, strand3)))
strand_pairs_comp_constraint = nc.rna_duplex_strand_pairs_constraint(
threshold=-7.0,
temperature=52,
short_description='StrandPairCompl',
pairs=[(strand0, strand2), (strand0, strand3), (strand1, strand2),
(strand1, strand3)])
strand_individual_ss_constraint = nc.nupack_strand_complex_free_energy_constraint(
threshold=-0.0, temperature=52, short_description='StrandSS')
params = ns.SearchParameters(
constraints=[
strand_pairs_no_comp_constraint,
strand_pairs_comp_constraint,
strand_individual_ss_constraint,
# dc.domains_not_substrings_of_each_other_domain_pair_constraint(),
],
# weigh_violations_equally=True,
out_directory=args.directory,
restart=args.restart,
# force_overwrite=True,
report_only_violations=False,
random_seed=1,
)
ns.search_for_dna_sequences(design=design, params=params)
def main() -> None:
args: CLArgs = parse_command_line_arguments()
# dc.logger.setLevel(logging.DEBUG)
nc.logger.setLevel(logging.INFO)
random_seed = 1
# many 4-domain strands with no common domains, 4 domains each, every domain length = 10
# just for testing parallel processing
# num_strands = 3
# num_strands = 5
# num_strands = 10
# num_strands = 50
num_strands = 100
# num_strands = 355
design = nc.Design()
# si wi ni ei
# strand i is [----------|----------|----------|---------->
for i in range(num_strands):
design.add_strand([f's{i}', f'w{i}', f'n{i}', f'e{i}'])
some_fixed = False
# some_fixed = True
if some_fixed:
# fix all domains of strand 0 and one domain of strand 1
for domain in design.strands[0].domains:
domain.set_fixed_sequence('ACGTACGTAC')
design.strands[1].domains[0].set_fixed_sequence('ACGTACGTAC')
parallel = False
# parallel = True
numpy_constraints: List[NumpyConstraint] = [
nc.NearestNeighborEnergyConstraint(-9.3, -9.0, 52.0),
# nc.BaseCountConstraint(base='G', high_count=1),
# nc.BaseEndConstraint(bases=('C', 'G')),
# nc.RunsOfBasesConstraint(['C', 'G'], 4),
# nc.RunsOfBasesConstraint(['A', 'T'], 4),
# nc.BaseEndConstraint(bases=('A', 'T')),
# nc.BaseEndConstraint(bases=('C', 'G'), distance_from_end=1),
# nc.BaseAtPositionConstraint(bases='T', position=3),
# nc.ForbiddenSubstringConstraint(['GGGG', 'CCCC']),
# nc.RestrictBasesConstraint(bases=['A', 'T', 'C']),
]
# def nupack_binding_energy_in_bounds(seq: str) -> bool:
# energy = dv.binding_complement(seq, 52)
# nc.logger.debug(f'nupack complement binding energy = {energy}')
# return -11 < energy < -9
#
# # list of functions:
# sequence_constraints: List[SequenceConstraint] = [
# # nupack_binding_energy_in_bounds,
# ]
replace_with_close_sequences = True
# replace_with_close_sequences = False
domain_pool_10 = nc.DomainPool(
f'length-10_domains',
10,
numpy_constraints=numpy_constraints,
replace_with_close_sequences=replace_with_close_sequences,
)
domain_pool_11 = nc.DomainPool(
f'length-11_domains',
11,
numpy_constraints=numpy_constraints,
replace_with_close_sequences=replace_with_close_sequences,
)
if some_fixed:
for strand in design.strands[
1:]: # skip all domains on strand 0 since all its domains are fixed
for domain in strand.domains[:2]:
if domain.name != 's1': # skip for s1 since that domain is fixed
domain.pool = domain_pool_10
for domain in strand.domains[2:]:
domain.pool = domain_pool_11
else:
for strand in design.strands:
for domain in strand.domains[:2]:
domain.pool = domain_pool_10
for domain in strand.domains[2:]:
domain.pool = domain_pool_11
# have to set nupack_complex_secondary_structure_constraint after DomainPools are set,
# so that we know the domain lengths
strand_complexes = [
nc.Complex(strand) for i, strand in enumerate(design.strands[2:])
]
strand_base_pair_prob_constraint = nc.nupack_complex_base_pair_probability_constraint(
strand_complexes=strand_complexes)
domain_nupack_ss_constraint = nc.nupack_domain_complex_free_energy_constraint(
threshold=-0.0, temperature=52, short_description='DomainSS')
domain_pairs_rna_duplex_constraint = nc.rna_duplex_domain_pairs_constraint(
threshold=-2.0, temperature=52, short_description='DomainPairRNA')
domain_pair_nupack_constraint = nc.nupack_domain_pair_constraint(
threshold=-0.5,
temperature=52,
short_description='DomainPairNUPACK',
parallel=parallel)
strand_pairs_rna_duplex_constraint = nc.rna_duplex_strand_pairs_constraint(
threshold=-1.0,
temperature=52,
short_description='StrandPairRNA',
parallel=parallel)
strand_individual_ss_constraint = nc.nupack_strand_complex_free_energy_constraint(
threshold=-1.0,
temperature=52,
short_description='StrandSS',
parallel=parallel)
strand_individual_ss_constraint2 = nc.nupack_strand_complex_free_energy_constraint(
threshold=-1.0,
temperature=52,
short_description='StrandSS2',
parallel=parallel)
strand_pair_nupack_constraint = nc.nupack_strand_pairs_constraint(
threshold=3.0,
temperature=52,
short_description='StrandPairNUPACK',
parallel=parallel,
weight=0.1)
params = ns.SearchParameters(
constraints=[
# domain_nupack_ss_constraint,
# strand_individual_ss_constraint,
# strand_individual_ss_constraint2,
strand_pairs_rna_duplex_constraint,
# strand_pair_nupack_constraint,
# domain_pair_nupack_constraint,
# domain_pairs_rna_duplex_constraint,
# strand_base_pair_prob_constraint,
# nc.domains_not_substrings_of_each_other_constraint(),
],
out_directory=args.directory,
restart=args.restart,
random_seed=random_seed,
max_iterations=None,
save_sequences_for_all_updates=True,
save_report_for_all_updates=True,
save_design_for_all_updates=True,
force_overwrite=True,
scrolling_output=False,
# report_only_violations=False,
)
ns.search_for_dna_sequences(design, params)
def four_g_constraint_summary(strand: nc.Strand):
violation_str = "" if 'GGGG' not in strand.sequence() else "** violation**"
return f"{strand.name}: {strand.sequence()}{violation_str}"
four_g_constraint = nc.StrandConstraint(description="4GConstraint",
short_description="4GConstraint",
evaluate=four_g_constraint_evaluate,
strands=tuple(strands), )
# Constraints
constraints = [
g_5_s_5_6_complex_constraint,
g_5_s_2_5_complex_constraint,
t_2_5_w_5_complex_constraint,
waste_2_5_complex_constraint,
reporter_6_complex_constraint,
f_waste_6_complex_constraint,
]
constraints.append(four_g_constraint)
seesaw_design = nc.Design(strands=strands)
params = ns.SearchParameters( # weigh_violations_equally=True,
constraints=constraints,
# report_delay=0.0,
out_directory='output/seesaw_gate',
report_only_violations=False, )
ns.search_for_dna_sequences(design=seesaw_design, params=params)