Fragmentomics

The frag command runs fragmentomics workflows. If no sub-workflow flag is provided, CFTK attempts all configured fragmentomics analyses.

Install the fragmentomics Python dependencies before using this command:

python -m pip install ".[fragmentomics]"

cftk --config cftk_init.json frag

Sub-Workflows

--occupancy

Run DANPOS-style nucleosome occupancy analysis.

--wps

Compute window protection score features.

--delfi

Run DELFI-style fragment ratio features through finaletoolkit.

--end-motif

Run k-mer end motif analysis through finaletoolkit.

--cleavage

Run CTCF cleavage analysis through finaletoolkit.

Examples

Run only WPS:

cftk --config cftk_init.json frag --wps

Run occupancy and DELFI:

cftk --config cftk_init.json frag --occupancy --delfi

Assay-Aware Scope

The default Twist Human Methylome profile is targeted. In auto mode, CFTK uses the covered-target BED to make panel-read BAMs for WPS, occupancy, and DELFI, clips the WPS/occupancy region BED, and clips the DELFI bins. The derived files and exact samtools commands are kept under results/4_fragmentomics/_scope/<scope-id>/ and recorded in the command ledger. These are panel-restricted features and must not be interpreted as genome-wide WPS, occupancy, or the original genome-wide DELFI score. Each scoped output directory also contains fragmentomics_scope.json. It is the beginner-facing record of the resolved mode, target BED and checksum, clipped interval counts, input signatures, and the interpretation warning:

python -m json.tool results/4_fragmentomics/wps/fragmentomics_scope.json

The command prints the same scope note before running. The historical DELFI figure filename contains _genome for compatibility; its title includes the resolved scope and it must not be read as proof of genome-wide coverage.

Inspect the resolved choice before running:

cftk --config cftk_init.json plan --preset fragmentomics
cftk --config cftk_init.json analyze --preset fragmentomics --dry-run

For a custom targeted profile, select panel scope explicitly. For a validated whole-genome project, the advanced override is explicit and appears in the provenance manifest:

cftk --config cftk_init.json frag --wps --fragmentomics-scope panel
cftk --config cftk_init.json analyze --preset fragmentomics \
   --fragmentomics-scope genome

End-motif and cleavage commands retain their existing inputs; the automatic panel restriction described here applies specifically to WPS, occupancy, and DELFI.

Reference Inputs

Fragmentomics workflows use different reference files:

• chrom_sizes for genomic intervals and bigWig/binned workflows.

• genome_2bit for DELFI and some finaletoolkit commands.

• tss_pas_bed for WPS and occupancy regions.

• ctcf_bed for cleavage.

• blacklist, gap, and bins for DELFI-style features.

Outputs are written under:

<output_dir>/results/4_fragmentomics/

Expected Outputs

The sub-workflows have different primary artifacts. A matrix is created for occupancy and WPS when more than one sample is available; use the merge command for modalities that return per-sample tables.

Fragmentomics output contract

Sub-workflow	Primary files	Directory
occupancy	<sample>.occupancy.tsv, <sample>.bw, and occupancy_matrix.tsv for multi-sample runs, plus fragmentomics_scope.json	results/4_fragmentomics/occupancy/
WPS	<sample>.wps.tsv and wps_matrix.tsv for multi-sample runs, plus fragmentomics_scope.json	results/4_fragmentomics/wps/
DELFI	<sample>_delfi.tsv (the historical companion figure name contains _genome); merge to delfi_matrix.tsv when needed, plus fragmentomics_scope.json	results/4_fragmentomics/delfi/
end motif	<sample>_<kmer>mer.tsv	results/4_fragmentomics/end_motif/
cleavage	<sample>_cleavage.bw	results/4_fragmentomics/cleavage/

cftk vis --mode frag writes PNG/PDF summaries beside these directories, including occupancy, DELFI, end-motif, cleavage, and comparison plots when the corresponding inputs exist. The figure below is a real five-control/ five-sALS technical example. It includes the completed occupancy, WPS, DELFI, and end-motif outputs and explicitly marks cleavage as not run.

Observed output from five controls and five sALS samples. WPS, occupancy, and DELFI are restricted to reads and intervals overlapping the configured Twist target panel, so these are panel-overlap summaries rather than genome-wide measurements or the original genome-wide DELFI score. The run did not produce cleavage output. These are technical workflow outputs, not biological or clinical validation. The per-sample tables, matrices, and scope sidecars listed above are authoritative. Download the sanitized aggregate metadata: JSON.