Candidate generation

Generators construct candidate therapeutics from target sites. Antisense therapeutics derive their IDs from the design, independent of any target site. Generated IDs begin with aso:, gapmer:, or sirna: and encode the mechanism, layout where applicable, and strand sequences. Standard ACGT sequences use two-bit hexadecimal encoding with an explicit length; other accepted sequences use UTF-8 hexadecimal encoding. Candidate generation keeps one therapeutic per ID and a separate binding for every target site, so repeated sequences can share a design without losing sites. An optional chemistry attached to a strand contributes its ID to that therapeutic’s design ID. The representation of individual nucleotide modifications remains deferred.

class ASOkai.Antisense.AntisenseCandidateGenerator

Bases: ABC

Base class for modality-specific therapeutic candidate generation.

abstractmethod candidates_for_site(site)

Return candidates designed for one site.

Parameters:

site (Site)

Return type:

list[AntisenseTherapeutic]

generate(sites)

Generate candidates and their site bindings in input order.

Parameters:

sites (Iterable[Site])

Return type:

tuple[list[AntisenseTherapeutic], list[Binding]]

class ASOkai.Antisense.ASOCandidateGenerator(mechanism)

Bases: AntisenseCandidateGenerator

Generate one 5’-to-3’ reverse-complement ASO for each target site.

Parameters:

mechanism (MechanismOfAction)

candidates_for_site(site)

Return one reverse-complement ASO for site.

Parameters:

site (Site)

Return type:

list[AntisenseTherapeutic]

class ASOkai.Antisense.GapmerCandidateGenerator(mechanism, left_wing_length, gap_length, right_wing_length)

Bases: ASOCandidateGenerator

Generate one wing-gap-wing ASO for each target site.

Parameters:

• mechanism (MechanismOfAction)

• left_wing_length (int)

• gap_length (int)

• right_wing_length (int)

candidates_for_site(site)

Return one reverse-complement gapmer for site.

Parameters:

site (Site)

Return type:

list[AntisenseTherapeutic]

class ASOkai.Antisense.SiRNACandidateGenerator(mechanism)

Bases: AntisenseCandidateGenerator

Generate one siRNA duplex for each target site.

Parameters:

mechanism (MechanismOfAction)

candidates_for_site(site)

Return one complementary guide/passenger duplex for site.

Parameters:

site (Site)

Return type:

list[AntisenseTherapeutic]