Digital genomic footprinting

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Genomic DNase I footprinting enables quantitative, nucleotide-resolution delineation of sites of transcription factor occupancy within native chromatin. We combined sampling of >67 billion uniquely mapping DNase I cleavages from >240 human cell types and states to index, with unprecedented accuracy and resolution, human genomic footprints and thereby the sequence elements that encode transcription factor recognition sites.

Digital genomic footprinting


A web directory containing all of the material for download is available here. Note: the same versions of some of the processed data is also persistently hosted at ZENODO and the ENCODE Project Portal. All files correspond to human genome build GRChr38/hg38. See below for file format descriptions.

  • Metadata containing information about the 243 biosamples analyzed (excel) (corresponds to manuscript Supplementary Table 1)

  • Footprints identified in individual datasets (directory listing)
    For each of the 243 datasets you will find the files outlined below. We have organized the files into sub-directories corresponding to each dataset.

    Filename Description
    reads.(bam|bam.bai) BAM alignment file from DNase I experiment
    hotspots.bed.starch DNase I hotspots
    peaks.bed.starch DNase I peaks
    dm.json Dispersion model file
    qc.pdf QC plots of dispersion model
    interval.all.bedgraph.(gz|gz.tbi|starch) Per-nucleotide footprint statistics Observed cleavage counts (bigWig) Expected cleavage counts (bigWig) Per-nucleotide p-value (bigWig) Windowed p-value (bigWig) FPR adjusted p-values (bigWig)
    interval.all.fps.*.(bed|bed.gz|bed.gz.tbi|bb) FPR thresholded footprints

    Note: starch format requries BEDOPS to decompress

  • Per-nucleotide posterior footprint probability (gzipped bedgraph and tabix index)
    Each row contains the –log transformed posterior probability of footprint in each of the 243 datasets (used to create Fig. 1 of associated manuscript). Columns (biosamples) are in the same order as sample metadata file above (Supplementary Table 1). Genomic positions were excluded if no individual sample has a posterior footprint probability > 0.8.

    Note that this file is massive (~66Gb) and we have provided a TABIX-index alongside to facilitate remote access using tabix:

    [jvierstra@test0 $] tabix chr19:45,001,882-45,002,279
    chr19   45001881        45001882        0.0     1.585874187526315e-08   7.332801033044234e-12   1.1864528914884431e-08  2.4502702181905534e-05 ...
    chr19   45001886        45001887        7.63844553830495e-07    1.0648232517951328e-08  0.0     2.842170943040401e-14   6.063725059846092e-07 ...
    chr19   45001887        45001888        0.026677374186842684    2.448578051428285e-07   5.897504706808832e-13   4.969464839632565e-10   2.277549524620781e-05 ...

    Additionally, an example of how to remotely access and plot these data using Python can be found here.

  • Consensus footprints (gzipped bed and tabix index)
    Re-analysis of the individual datasets using an Emperical Bayesian framework.

    • Footprinted motif archetypes (gzipped bed and tabix index)
      Motif archetypes matches that overlap consensus footprints (see motif clustering for more information)

    • Footprint-by-biosample matrix
      Matrix delineating the occupancy of individual consensus footprints (row) in individual biosamples (columns). Biosamples (columns) in same order as sample metadata table.

  • Single nucleotide variants tested for allelic imbalance
    De novo genotypes derived from 147 individuals and allelic read counts for each variant in all 243 datasets. The assignment of each biosample to an individual is found in Supplementary Table 1 (above).

    • Genotype and allelic read depth for each biosample (gzipped vcf and tabix index)
      The file format is self-explantory (see header for description via bcftools view -h genotypes.vcf.gz)

    • Variants tested for imbalance (combining data by genotype) using Beta-binomial distribution (gzipped bed and tabix index)


All of the DGF data listed above can be loaded/visualized in the UCSC Genome Browser with the following trackhub (copy & paste into “My Hubs”):

Alternatively, you can click here to automatically load this trackhub at the Genome Browser hosted at UCSC.

Code & Tutorials

Software and scripts are available at GitHub.

Documentation is hosted at Read the docs. Included in the documentation are examples of how to remotely access, manipulate and visualize genomic footprinting data.


If you use this resource in your research, please cite:

Vierstra2020 Vierstra, J., Lazar, J., Sandstrom, R. et al. Global reference mapping of human transcription factor footprints. Nature 583, 729–736 (2020)


This work was funded through the NHGRI ENCODE Project (NIH grants U54HG007010 and 5UM1HG009444)

Appendix: File format descriptions

Hotspots and peaks

See hotspot2 documentation for file descriptions.

Per-nucleotide footprint statistics for individual datasets (interval.all.bedgraph.gz)

  Column Example Description
1 contig chr1 Chromosome
2 start 9823494 Start position (0-based)
3 stop 9823495 End position (start+1)
4 obs 24 Observed DNase I cleavages (both strands combined)
5 exp 56 Expected DNase I cleavages
6 lnp 2.1 –log p-value lower-tail negative binomial
7 winlp 14.5 –log p-value windowed test (Stouffer’s Z)
8 fdr 0.0014 Empircal false-discovery rate

Consensus footprints (consensus_footprints_and_collapsed_motifs_hg38.bed.gz)

  Column Example Description
1 contig chr10 Chromosome
2 start 97320044 Start position (0-based)
3 stop 97320056 End position (start+1)
4 identifier 10.754379.4 Unique identifier (DHS_chom#.DHS_position%.fp_position%; DHS_chrom#.DHS_position% = DHS index identifier)
5 mean_signal 55.865317 Mean footprint -log(1-posterior) across biosamples (“confidence score”)
6 num_samples 9 Number of unique biosamples contributing to this index footprint (posterior >= 0.99)
7 num_fps 9 Number of unique footprints across all samples that contributed to this consensus footprint
8 width 12 Width of consensus footprint (column 3-column 2)
9 summit_pos 97320049 Estimated footprint summit position
10 core_start 97320042 Start position of core-region containing 95% of per-biosample summits
11 core_end 97320053 End position of core-region containing 95% of per-biosample summits
12 motif_clusters CTCF;KLF/SP/2;ZNF563 Non-redundant motif archetype matches w/ 90% overlap, ; delimited

Note: A seperate version of this file is also available (consensus_footprints_and_motifs_hg38.bed.gz; gzipped bed and tabix index) where column 12 is the motifs that overlap (≥3np) footprints for all (not-collapsed) PWM models.

Footprinted motif archetypes (collapsed_motifs_overlapping_consensus_footprints_hg38.bed.gz)

  Column Example Description
1 contig chr1 Chromosome
2 start 1782520 Start position (0-based)
3 end 1782770 End position
4 motif_cluster TBX/4 Motif cluster name
5 score 0 BED-score field (not used)
6 strand + Strand (+ or -)
7 thickStart 1782520 Same as ‘start’
8 thickEnd 1782770 Same as ‘end’
9 itemRgb 0,28,255 RGB string for UCSC browser
10 best_model TBX20_TBX_1 Best matching motif model from cluster
11 match_score 5.4513 MOODS match score for best cluster match
12 DBD TBX DNA binding domain family
13 num_models 2 Number of motif models from cluster with a match

For more information about the motif archetypes see here.

Variants tested for imbalance (tested_snvs_padj.bed.gz)

  Column Example Description
1 contig chr10 Chromosome
2 start 404425 Start position (0-based)
3 end 404426 End position
4 ref G Reference allele
5 alt T Alternative allele
6 total_reads 558 Number of total reads over variant in het. samples
7 ref_reads 196 Number of reads mapped to reference allele
8 num_hets 6 Number of heterozygous biosamples
9 allelic_ratio 0.3513 Proportion reads mapping to reference allele
10 bb_test_stat 0.0017 Beta-binomial test statistic
11 adj_p 0.0468120827793 Adjusted p-value
12 dhs 1 Overlapping DHS peak (binary indicator)
13 fps 1 Overlapping consensus footprint (binary indicator)