Usability Comparison

This table summarizes workflow fit and usability boundaries. It is not a benchmark result.

Tool	Primary workflow	Direct FASTQ.gz input	Count matrix	One substitution	One insertion/deletion	Explicit ambiguous/no-match	Target audit	Notes
DotMatch	known short-target assignment	yes	yes	yes	yes	yes	yes	General engine for guides, barcodes, panels, whitelists
guide-counter	CRISPR guide counting	yes	yes	yes	no, per current docs	workflow-specific	no	Serious CRISPR comparator; compare directly for mismatch-only guide counting
MAGeCK count	CRISPR guide counting	yes	yes	exact FASTQ mode	no direct mismatch FASTQ route	limited	no	Downstream ecosystem standard
Cutadapt	adapter/search/trimming	yes	no	yes	yes	not assignment-centered	no	Workflow comparator, not assignment oracle
Bowtie2	reference alignment	yes	no	yes	yes	mapping-centered	no	Over-general for known short-target assignment
Edlib scan	exact pairwise oracle	no workflow shell	no	yes	yes	yes if wrapped	no	Exact semantic comparator; exhaustive over targets

Example Workflow

The target user-facing workflow is:

dotmatch count \
  --targets guides.csv \
  --reads sample.fastq.gz \
  --target-start 23 \
  --target-length 19 \
  --k 1 \
  --metric levenshtein \
  --indel-window 1 \
  --ambiguity-policy radius \
  --auto-offset 2 \
  --out counts.tsv \
  --summary summary.json \
  --ambiguous-out ambiguous.tsv \
  --unmatched-out unmatched.tsv

This should produce:

• count matrix for downstream analysis;

• deterministic assignment policy;

• ambiguity and unmatched diagnostics;

• exact Levenshtein semantics including one-base indels;

• a hamming mode for fair one-mismatch/no-indel guide-counter comparisons;

• selected guide offset in the summary JSON when auto-offset detection is used;

• reproducible validation against native Edlib scan.

Scope Boundary

DotMatch is not a universal replacement for guide-counter. Its current CRISPR positioning is:

Compared with mismatch-only guide counters, DotMatch provides a general exact Levenshtein assignment primitive with indel support, ambiguity semantics, target audit, native validation, and multi-domain known-target workflows.

Direct speed comparisons against guide-counter require a pinned guide-counter version, exact commands, and a workflow where the semantics being compared are clearly stated.