Base Editor Repair Outcome Simulator

Base Editor Configuration

Deaminase window exposure 70%

Repair Outcome Statistics

Trials run

Precise C→T

Reversion to C

Indel / byproduct

Unedited (C retained, no deamination this round) Precise edit — U read as T on replication Reversion — BER restores C (no edit) Indel — error-prone repair of abasic site

How it works

A cytosine base editor (CBE) is a Cas9 nickase fused to a cytidine deaminase (e.g. APOBEC1). Inside the R-loop opened by the sgRNA, the deaminase hydrolyses one exposed cytosine:

C + H2O --deaminase--> U + NH3
(cytosine)          (uracil, read as T by polymerases)

That reaction only fires with probability d (the "window exposure" slider) — the deaminase's catalytic window covers roughly protospacer positions 4-8, so a base near the window edge is converted less reliably. If deamination succeeds, the resulting U:G mismatch is resolved by one of three competing cellular pathways, modelled here as conditional probabilities:

P(precise C→T) = min(0.95, 0.20 + 0.45·u + 0.25·n)
P(reversion)   = (1-u) · 0.5 · (1 - 0.4·n)
P(indel)       = 1 - P(precise) - P(reversion)
  u = 1 if UGI fused, else 0
  n = 1 if the non-edited strand is nicked, else 0

UGI (uracil glycosylase inhibitor) — blocks uracil-N-glycosylase (UNG) from excising the U. Without it, base-excision repair (BER) often removes the uracil, leaving an abasic site that either reverts to C or is patched imprecisely into an indel.
Strand nick bias — nicking the non-edited (G-containing) strand directs mismatch repair to use the edited, U-containing strand as its template, pulling outcomes toward the clean T conversion instead of reversion.
Each "trial" is one editing attempt at the highlighted cytosine; the particle's flight path and landing bin show which of the four outcomes it drew.

This mirrors the real reason first-generation CBEs (BE1, no UGI/nick) gave low, impure editing while BE3 and later architectures — which add UGI and a strand-selective nick — raised precise C→T yields into the 30-70% range with far fewer indels.

C base A base G base T base Target cytosine

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