mdhewei/bioinfor-claw/design-base-editor-sgrnas

Base Editor sgRNA Design

Purpose

Design sgRNAs for base editing experiments. Given a gene symbol, fetch its coding exon sequences from Ensembl, identify all valid protospacers with a target base (C for CBE, A for ABE) in the editing window, score each guide, and return a ranked table with full annotation of editing outcomes.

Use when

• the user wants to design base editor sgRNAs for a gene
• the user mentions CBE, ABE, cytosine base editor, adenine base editor, base editing
• the user wants to introduce a specific point mutation (e.g., "install a stop codon", "correct a missense variant")
• the user wants to model a disease mutation via base editing
• the user asks about BE3, BE4max, ABE7.10, ABE8e, AncBE4max, or similar editors
• the user wants guides that avoid bystander edits

Do not use when

• the user wants standard CRISPR KO guides (use design-sgrnas-by-gene)
• the user wants prime editor pegRNA design (different mechanism)
• the user wants guides for a non-coding region without specifying coordinates
• the user wants CRISPRi or CRISPRa (dCas9-based, no editing window)

Supported editors and their properties

Positions are counted from the PAM-distal end (position 1 = most 5′ of protospacer).

Inputs

• --gene — gene symbol (e.g., TP53, KRAS, BRCA1). Required.
• --organism — human (default), mouse, or monkey
• --editor — editor name or type: CBE, ABE, dual, BE3, BE4max, ABE7.10, ABE8e, NG-CBE, NG-ABE, SpRY-CBE, SpRY-ABE (default: CBE)
• --window-start — editing window start position (default: editor-specific)
• --window-end — editing window end position (default: editor-specific)
• --pam — PAM sequence: NGG (default), NG, or NRN
• --region — sequence scope: cds (coding sequence only, default), exon (all exons), transcript
• --allow-bystander — include guides with bystander C/A in window (default: False)
• --max-bystander — max allowed bystander editable bases (default: 0; use 1-2 if --allow-bystander)
• --top-n — number of top guides to return (default: 20)
• --transcript-id — restrict to a specific Ensembl transcript ID
• --target-aa-pos — target a specific amino acid position (e.g., 12 for KRAS G12)
• --outdir — output directory (default: ./base_editor_results/)
• --prefix — output file prefix (default: gene symbol)

Outputs

Guide table columns

Execution

# Basic CBE guide design for TP53
python scripts/design_base_editor_sgrnas.py \
  --gene TP53 \
  --editor CBE \
  --outdir results/
 
# ABE8e guides for KRAS, targeting codon 12
python scripts/design_base_editor_sgrnas.py \
  --gene KRAS \
  --editor ABE8e \
  --target-aa-pos 12 \
  --outdir results/
 
# Dual-base editor, no bystander edits allowed
python scripts/design_base_editor_sgrnas.py \
  --gene EGFR \
  --editor dual \
  --allow-bystander \
  --max-bystander 1 \
  --outdir results/
 
# Mouse gene, NG-CBE with relaxed PAM
python scripts/design_base_editor_sgrnas.py \
  --gene Trp53 \
  --organism mouse \
  --editor NG-CBE \
  --pam NG \
  --outdir results/

Parameter decision guide