(a) An example of how to score a gRNA-target pair with two mismatches. First the
gRNA-target pair is broken down into two single-mismatch pseudo-pairs, each of
which is scored with the first layer (single mismatch) model, . Then these scores are combined with the
second-layer model, , yielding a single gRNA-target score that
accounts for all mismatches. (b) An example of how to aggregate the
set of gRNA-target scores for a single gRNA into one summary off-target score
for a gRNA. The aggregator model, a(), computes statistics of
the input distribution of gRNA-target scores as features and runs them through a
model, producing the aggregate score for a gRNA (e.g.
0.78).