Generate therapeutic candidates

The step currently supports ASO and gapmer designs. siRNA candidate generation is not implemented; selecting sirna fails during parameter validation.

Select the modality with parameters.antisense.modality.type and place its mechanism at parameters.antisense.modality.mechanism and its design settings under parameters.antisense.modality.design. For example, the CLI selects a gapmer with --param antisense.modality.type=aso and --param antisense.modality.design.type=gapmer, followed by its segment lengths. The gapmer design rules apply to the ASO modality.

Generates therapeutic candidates for target sites.

Step type:: Core step

Run this step

ASOkai run --step generate-therapeutic-candidates --config-file ./config.yaml

Example configuration for this step and its dependencies:

datadir: ./data
parameters:
  genome:
    assembly: GRCh38
    release: 114
    source: ensembl
    species: Homo_sapiens
  target:
    target_id: ENSG00000133703
    k: 16
    region: pre-mrna
  antisense:
    modality:
      type: aso
      design:
        type: gapmer
        left_wing_length: 3
        gap_length: 10
        right_wing_length: 3
      mechanism: rnase-h1

Parameters

These scalar configuration values are passed to this step.

Common parameters

Configuration path	Details
`parameters.target.k`	Accepted value: integer; minimum: 1 Requirement: Required Description: Target-site length.
`parameters.antisense.modality.type`	Accepted value: string; minimum string length: 1 Requirement: Required Description: Antisense therapeutic modality.
`parameters.antisense.modality.mechanism`	Accepted value: string; minimum string length: 1 Requirement: Required Description: Therapeutic mechanism of action for the selected modality.

Designs

Gapmer design

Set parameters.antisense.modality.type to aso and parameters.antisense.modality.design.type to gapmer.

Example configuration:

parameters:
  antisense:
    modality:
      type: aso
      design:
        type: gapmer
        left_wing_length: 3
        gap_length: 10
        right_wing_length: 3

Configuration path	Details
`parameters.antisense.modality.design.left_wing_length`	Accepted value: integer; minimum: 1 Requirement: Required when parameters.antisense.modality.design.type is gapmer Description: Number of nucleotides in the left gapmer wing. Required for a gapmer design and not used by an unmodified design.
`parameters.antisense.modality.design.gap_length`	Accepted value: integer; minimum: 1 Requirement: Required when parameters.antisense.modality.design.type is gapmer Description: Number of nucleotides in the central gapmer gap. Required for a gapmer design and not used by an unmodified design.
`parameters.antisense.modality.design.right_wing_length`	Accepted value: integer; minimum: 1 Requirement: Required when parameters.antisense.modality.design.type is gapmer Description: Number of nucleotides in the right gapmer wing. Required for a gapmer design and not used by an unmodified design.

Unmodified design

Set parameters.antisense.modality.type to aso and parameters.antisense.modality.design.type to unmodified.

Example configuration:

parameters:
  antisense:
    modality:
      type: aso
      design:
        type: unmodified

This option has no additional parameters.

Parameter rules

exactly one of these config values is required: target_id, target_name

Inputs

An input with a fixed producer uses that output by default. A selected run can instead link a named output or supply an existing path. The input’s path override in config.yaml also selects an existing file. External paths are validated against the input’s file contract.

File input	Details
`target_gene`	Producer output: create-target-gene.`target_gene` Shared config source: `steps.generate-therapeutic-candidates.inputs.target_gene.path` or `steps.generate-therapeutic-candidates.inputs.target_gene.from` Format: JSON — `TargetGene` Description: Serialized target gene object from create-target-gene.

Example path-override configuration:

steps:
  generate-therapeutic-candidates:
    inputs:
      target_gene:
        path: /path/to/target_gene.json

Resources

Configurable resources use the first value in the resolution order shown below.

Resource setting	Details
`memory_mb`	Step override: `resources.generate-therapeutic-candidates.memory_mb` Shared default: `resources.default.memory_mb` Built-in fallback: 4096 Accepted value: integer; minimum: 1 Description: Memory in mebibytes allocated to this step.

Outputs

File output paths are relative to datadir. Braced names are replaced with the corresponding parameter values.

File outputs

File output

Details

therapeutics

Format: JSON — list[ASO or Gapmer or siRNA]

Description: Serialized therapeutic candidates.

Path template: {assembly}/{source}/{release}/targets/{target}/antisense/{target}_k{k}_{region}_{modality}_{design}_l{left}_g{gap}_r{right}_{mechanism}_therapeutics.json

Example path: GRCh38/ensembl/114/targets/ENSG00000133703/antisense/ENSG00000133703_k16_pre-mrna_aso_gapmer_l3_g10_r3_rnase-h1_therapeutics.json

bindings

Format: JSON — list[Binding]

Description: Serialized relationships between therapeutic IDs and input target-site IDs.

Path template: {assembly}/{source}/{release}/targets/{target}/antisense/{target}_k{k}_{region}_{modality}_{design}_l{left}_g{gap}_r{right}_{mechanism}_bindings.json

Example path: GRCh38/ensembl/114/targets/ENSG00000133703/antisense/ENSG00000133703_k16_pre-mrna_aso_gapmer_l3_g10_r3_rnase-h1_bindings.json