Overview
A UCSC CRISPR track is three files:
File |
What it is |
|---|---|
|
bigBed ( |
|
bgzip-compressed per-guide off-target lists |
|
the bgzip |
The column schema, cas12aTargets.as, is a fixed autoSql file kept in the repo and passed to
bedToBigBed at build time. It is not a per-genome output.
Each bigBed row stores a guide’s coordinates, color, on-target scores, off-target specificity, and an
_offset: a byte offset into the uncompressed crisprDetails.tab. Clicking a guide makes the browser
seek that offset (via the .gzi index) and render the off-target list. _offset = 0 means no list is
stored, the guide is either non-unique or already perfectly specific (see
Off-target records).
Cas12a specifics
PAM is 5’, 4 nt (
TTTV), opposite end from Cas9’s 3’NGG.V = A/C/G.A guide site spans PAM(4) + spacer(23) = 27 nt; the spacer is the bigBed “thick” region.
We score with two CFD off-target matrices in one pass, enCas12a (WT) and AsCas12a/2xNLS.
The off-target asymmetry that drives the index
The guide PAM is TTTV (the strong, canonical set). The off-target index uses TTTN, because
enCas12a also cleaves the weak TTTT PAM.
Note
Throughout, “specificity” is an aggregate over a guide’s per-off-target CFD scores: 1.0 = perfectly unique, lower = more / closer off-targets. On-target scores (DeepCpf1 and friends) are a separate axis predicting cutting efficiency.
References
Off-target CFD matrices DeWeirdt et al. 2021 (cas12a_manuscript code)
On-target models DeepCpf1 Kim et al. 2018; EnPAM-GB DeWeirdt et al. 2021; enseq-DeepCpf1 / seq-DeepCpf1variants Chen et al. 2025