Hit bead collection
quantitation by sequence analysis. Standards
of positive control pepstatin A beads 1 were prepared
by FACS in known lot sizes (30, 100, 300, 1000, 3000; blue hues).
The DNA encoding tags of standard lots and the hit bead collection
were each amplified in bulk and sequenced. Sequencing coverage for
the hit bead collection and 3000-bead lot were 6-fold lower than other
standard lots (30, 100, 300, 1000). Reads were aligned to a degenerate
reference sequence, edited for single-base errors, aggregated by sequence,
and counted by the N8 UMI after enforcing a Hamming distance
of >1 per UMI. (A) Unique encoding sequences were rank ordered
and
plotted by UMI counts (bead index). Each plot contained an inflection
(large data point) as the bead index approached the known lot size.
(B) A normal weighted average UMI value (UMIw) was generated
for each bead index, and the inflection point for each curve was approximated
at the bead index yielding a maximum ΔUMIw/UMIw (% change in UMI; inset). The inflection x coordinate is the bead index cutoff (25, 84, 270, 861, 1863, 2681).