Download ENCODE Files

When to Use

• User wants to download ENCODE data files to their local machine
• User asks to "download", "get", or "fetch" ENCODE files
• User needs specific file formats (BED, FASTQ, BAM, bigWig) from experiments
• User wants to batch download files matching search criteria
• User needs to verify file integrity after download (MD5 checksums)
• User asks about organizing downloaded files by experiment or format

Help the user download ENCODE data files to their local machine.

Download Strategy

1. Specific files by accession: Use

   encode_download_files

   with file accession IDs (e.g., "ENCFF635JIA").

2. Batch download by criteria: Use

   encode_batch_download

   to search and download in one step.
   • Always start with

     dry_run=True

     (default) to preview what will be downloaded
   • Show the user the file count, total size, and file list
   • Only proceed with

     dry_run=False

     after user confirms

3. Download organization options:

   • "flat"

     : All files in one directory

   • "experiment"

     : Organized by experiment accession (recommended)

   • "format"

     : Organized by file format

   • "experiment_format"

     : Organized by experiment, then format

Important Notes

• All downloads include MD5 verification by default (

  verify_md5=True

  )
• Ask the user for a download directory if not specified
• Warn about large downloads (>1GB total or >50 files)
• Files already downloaded will be skipped (idempotent)
• For restricted files, credentials must be configured first via

  encode_manage_credentials

Pitfalls & Edge Cases

1. Disk space: BAM files can be 5-50GB each; FASTQ files 1-20GB. Before any batch download, warn the user about estimated total size from the dry_run preview. A single ChIP-seq experiment can produce 10-30GB of raw data files.
2. MD5 verification failures: If MD5 verification fails, the file may be corrupted or incompletely downloaded. Always re-download rather than skipping verification. Never set

   verify_md5=False

   unless the user explicitly requests it and understands the risk.
3. Downloading too much data: Users often request BAM files when they only need peak calls or signal tracks. Suggest

   preferred_default=True

   to get ENCODE's recommended files, or filter by

   output_type

   (e.g., "IDR thresholded peaks", "fold change over control") to avoid downloading raw data unnecessarily.
4. Restricted/unreleased data: Files with status other than "released" may require ENCODE credentials. Use

   encode_manage_credentials(action="check")

   to verify credentials are configured before attempting to download restricted data.
5. Mixed assemblies in batch download: Always specify the

   assembly

   filter (e.g., "GRCh38") in batch downloads. Without it, you may download files aligned to different genome assemblies (hg19, GRCh38, mm10), making downstream analysis impossible.
6. Timeout on large files: For downloading many files or very large files,

   encode_batch_download

   handles retries and concurrent downloads better than individual

   encode_download_files

   calls. The default limit of 100 files provides a safety cap.

File Type Guide

When users request "files" without specifying a type, use this priority to suggest the right output_type:

• Peak analysis:

  output_type="IDR thresholded peaks"

  (most stringent, recommended for ChIP-seq/ATAC-seq)
• Signal visualization:

  file_format="bigWig"

  ,

  output_type="fold change over control"

  (for genome browser tracks)
• Gene expression:

  output_type="gene quantifications"

  (for RNA-seq TPM/FPKM tables)
• Raw data reprocessing:

  file_format="fastq"

  (only when user needs to run their own pipeline)
• Quick defaults:

  preferred_default=True

  (ENCODE's recommended files for any experiment)

What to Download for Each Analysis

Assay-Specific Recommendations

File Selection Priority

When multiple files exist for the same experiment, choose files in this priority order:

1. preferred_default=True: ENCODE curators mark recommended files. Always prefer these when available. Use

   encode_list_files(experiment_accession="ENCSR...", preferred_default=True)

   to find them.

2. Peak file hierarchy (most to least stringent):

   • IDR thresholded peaks — replicated, irreproducibility-filtered (gold standard)
   • Optimal IDR thresholded peaks — union of replicate-level peaks
   • Conservative IDR thresholded peaks — intersection of replicate-level peaks
   • Pseudoreplicated peaks — peaks from pooled pseudoreplicates
   • Replicated peaks — peaks found in both replicates (broad marks)

3. Signal track hierarchy:

   • fold change over control — normalized signal, best for comparing across experiments
   • signal p-value — statistical significance of enrichment
   • signal of unique reads — uniquely mapped read signal
   • signal of all reads — includes multi-mapped reads (noisier)

4. Assembly preference:

   • GRCh38 for human (current standard) — always use this
   • hg19 for human (legacy) — only if collaborators require it
   • mm10 for mouse (current standard)
   • Never mix assemblies within an analysis

5. Replicate preference:

   • Replicated files (combined replicates) over single-replicate files
   • Biological replicates over technical replicates
   • Isogenic replication over anisogenic

6. Status preference:

   • released — fully validated, use these
   • archived — older versions, avoid unless specifically needed
   • revoked — quality issues found, never use

Storage Estimates

Plan disk space before downloading. Use

dry_run=True

Rule of thumb: Peak files and quantifications are small (MB). Signal tracks are medium (hundreds of MB). Alignments and raw reads are large (GB to tens of GB). Always preview with

dry_run=True

Walkthrough: Downloading a Complete ChIP-seq Dataset

This walkthrough shows the full process for downloading H3K27ac ChIP-seq data from human pancreas tissue.

Step 1: Find the experiment

encode_search_experiments(
  assay_title="Histone ChIP-seq",
  target="H3K27ac",
  organ="pancreas",
  biosample_type="tissue",
  assembly="GRCh38"
)
  -> Returns experiments, e.g., ENCSR831JOY

Step 2: List available files

encode_list_files(
  experiment_accession="ENCSR831JOY",
  assembly="GRCh38"
)
  -> Returns all files: FASTQs, BAMs, peaks, signals
  -> Note the file accessions for the files you need

Step 3: Identify the right files

Filter to what you actually need — usually peaks + signal tracks:

encode_list_files(
  experiment_accession="ENCSR831JOY",
  assembly="GRCh38",
  preferred_default=True
)
  -> Returns ENCODE-recommended files only
  -> Typically: IDR peaks (bed) + fold change signal (bigWig)

Or be specific about output types:

encode_list_files(
  experiment_accession="ENCSR831JOY",
  output_type="IDR thresholded peaks",
  assembly="GRCh38"
)
  -> Returns only IDR peak files, e.g., ENCFF635JIA

Step 4: Download with MD5 verification

encode_download_files(
  file_accessions=["ENCFF635JIA", "ENCFF388RZD"],
  download_dir="/Users/you/data/encode/h3k27ac_pancreas",
  organize_by="experiment",
  verify_md5=True
)
  -> Downloads files with integrity verification
  -> Creates: download_dir/ENCSR831JOY/ENCFF635JIA.bed.gz
              download_dir/ENCSR831JOY/ENCFF388RZD.bigWig

Step 5: Verify the download results

Check the returned JSON for:

• summary.successful

  — number of files downloaded

• summary.failed

  — should be 0

• summary.total_size_human

  — total bytes downloaded
• Each file's

  md5_verified

  — should be True for all files

If any file fails MD5 verification, re-download that specific file. Do not proceed with a corrupted file.

Step 6: Log provenance

Track the experiment and log where the data came from:

encode_track_experiment(
  accession="ENCSR831JOY",
  notes="H3K27ac ChIP-seq, pancreas tissue, downloaded for enhancer analysis"
)
  -> Stores experiment metadata, publications, and pipeline info locally

If you create derived files later (e.g., filtered peaks), log them too:

encode_log_derived_file(
  file_path="/Users/you/data/encode/h3k27ac_pancreas/filtered_peaks.bed",
  source_accessions=["ENCSR831JOY", "ENCFF635JIA"],
  description="H3K27ac peaks filtered against ENCODE Blacklist v2",
  file_type="filtered_peaks",
  tool_used="bedtools intersect v2.31.0",
  parameters="bedtools intersect -v -a ENCFF635JIA.bed.gz -b hg38-blacklist.v2.bed"
)

Walkthrough: Batch Download for Multi-Experiment Analysis

Use

encode_batch_download

Step 1: Preview with dry run

Always start with

dry_run=True

encode_batch_download(
  download_dir="/Users/you/data/encode/h3k4me3_multi_tissue",
  output_type="IDR thresholded peaks",
  target="H3K4me3",
  assembly="GRCh38",
  assay_title="Histone ChIP-seq",
  biosample_type="tissue",
  organize_by="experiment",
  dry_run=True
)
  -> Preview: 42 files, 180MB total, from 42 experiments
  -> Shows file list with accessions, sizes, and experiment info

Step 2: Review and confirm

Present the dry run results to the user:

• Total file count and size
• Breakdown by experiment or tissue
• Any unexpected files (wrong assembly, archived status)

If the count is too large, narrow with additional filters (e.g., add

organ="pancreas"

Step 3: Execute the download

encode_batch_download(
  download_dir="/Users/you/data/encode/h3k4me3_multi_tissue",
  output_type="IDR thresholded peaks",
  target="H3K4me3",
  assembly="GRCh38",
  assay_title="Histone ChIP-seq",
  biosample_type="tissue",
  organize_by="experiment",
  dry_run=False
)
  -> Downloads all 42 files with MD5 verification
  -> Creates: download_dir/ENCSR.../ENCFF....bed.gz (one per experiment)

Step 4: Handle failed downloads

If some files fail:

• Check the

  errors

  array in the response for specific failure reasons
• Network timeouts: retry the failed accessions with

  encode_download_files

• MD5 mismatches: re-download the specific files
• 403/404 errors: the file may be restricted or withdrawn from ENCODE

encode_download_files(
  file_accessions=["ENCFF_FAILED_1", "ENCFF_FAILED_2"],
  download_dir="/Users/you/data/encode/h3k4me3_multi_tissue",
  organize_by="experiment",
  verify_md5=True
)

Organization strategies

Choose

organize_by

"experiment"

download_dir/ENCSR.../files

"format"

download_dir/bed/files

download_dir/bigWig/files

"experiment_format"

download_dir/ENCSR.../bed/files

"flat"

download_dir/files

Gotchas

1. Assembly mismatch: Always specify

   assembly="GRCh38"

   for human or

   assembly="mm10"

   for mouse. Omitting this in batch downloads can produce a mix of GRCh38 and hg19 files that cannot be compared. There is no automated liftover in the download tools — you must use the

   liftover-coordinates

   skill separately if you need to convert between assemblies.

2. File status matters: Only

   status="released"

   files are fully validated by ENCODE. Archived files may have been superseded by newer processing. Revoked files had quality issues discovered after release. Always check file status before using data in analysis.

3. MD5 verification is not optional: Corrupted files produce silent errors in downstream analysis — wrong peak counts, shifted signal tracks, truncated alignments. The few extra seconds for MD5 verification prevents hours of debugging. Only disable with

   verify_md5=False

   if you are re-downloading a file you already verified.

4. Streaming for large files: BAM and FASTQ files are downloaded with streaming to avoid loading entire files into memory. The

   encode_batch_download

   tool handles this automatically. If a download is interrupted, re-running the same command will skip already-completed files (idempotent).

5. The 100-file safety limit:

   encode_batch_download

   defaults to

   limit=100

   to prevent accidentally downloading thousands of files. If your query returns more than 100 files, narrow your filters or run multiple targeted batches. You can increase the limit explicitly if you have confirmed the download is intentional.

6. preferred_default may return nothing: Not all experiments have files marked as

   preferred_default=True

   . If this filter returns empty results, fall back to filtering by specific

   output_type

   and

   assembly

   instead.

7. Credential requirements: Files with status "in progress" or "submitted" require ENCODE DCC credentials. Use

   encode_manage_credentials(action="check")

   before attempting restricted downloads. Contact the ENCODE DCC for access to unreleased data.

8. Duplicate files across experiments: When downloading the same file type across many experiments, some control files (e.g., input ChIP-seq) may be shared between experiments. The download tool skips already-existing files, so shared controls will not be downloaded twice.

Code Examples

1. Smart download: "Download IDR thresholded peaks for H3K4me3 ChIP-seq in GRCh38"

Step 1: Preview with dry run
  encode_batch_download(
    download_dir="/Users/you/data/encode",
    output_type="IDR thresholded peaks",
    target="H3K4me3",
    assembly="GRCh38",
    assay_title="Histone ChIP-seq",
    dry_run=True
  )
  -> Shows: 18 files, 45MB total (peak files are small)
  -> Present file list to user for confirmation

Step 2: Confirm and download
  encode_batch_download(
    download_dir="/Users/you/data/encode",
    output_type="IDR thresholded peaks",
    target="H3K4me3",
    assembly="GRCh38",
    assay_title="Histone ChIP-seq",
    dry_run=False
  )
  -> Downloads with MD5 verification, skips already-downloaded files

2. Batch download with preview: "Download all ATAC-seq bigWig signal tracks for pancreas"

Step 1: Dry run to see what's available
  encode_batch_download(
    download_dir="/Users/you/data/encode/atac_pancreas",
    file_format="bigWig",
    assay_title="ATAC-seq",
    organ="pancreas",
    assembly="GRCh38",
    organize_by="experiment",
    dry_run=True
  )
  -> Review: 24 files, 8.3GB total, from 6 experiments

Step 2: Download after user confirms
  (same call with dry_run=False)

3. Organized download: "Download files organized by experiment and format"

Step 1: Download specific files with organization
  encode_download_files(
    file_accessions=["ENCFF635JIA", "ENCFF388RZD", "ENCFF901ABC"],
    download_dir="/Users/you/data/encode",
    organize_by="experiment_format"
  )
  -> Creates: download_dir/ENCSR.../bed/file.bed.gz
             download_dir/ENCSR.../bigWig/file.bigWig

4. ENCODE-recommended defaults: "Just get the recommended files for this experiment"

encode_batch_download(
  download_dir="/Users/you/data/encode/defaults",
  preferred_default=True,
  assembly="GRCh38",
  assay_title="Histone ChIP-seq",
  target="H3K27me3",
  organ="liver",
  organize_by="experiment",
  dry_run=True
)
  -> Returns only ENCODE-curated default files
  -> Typically the most useful subset for standard analyses

5. RNA-seq expression data: "Download gene quantification tables"

encode_batch_download(
  download_dir="/Users/you/data/encode/rnaseq_brain",
  output_type="gene quantifications",
  assay_title="total RNA-seq",
  organ="brain",
  assembly="GRCh38",
  organize_by="experiment",
  dry_run=True
)
  -> Preview: TSV files with TPM/FPKM values, typically 5-20MB each

Integration

Presenting Results

When presenting download results to the user:

• Show a download summary table: filename | size | format | MD5 status | path
• For

  dry_run=True

  , present what WOULD be downloaded with total size estimate and file count
• Report any failures separately with error messages
• After successful downloads, suggest next steps:
  • "Would you like to log these as tracked experiments?" (use

    encode_track_experiment

    )
  • "Would you like to log any derived files for provenance?" (use

    encode_log_derived_file

    )
• For large batch downloads, summarize by experiment and format rather than listing every file

Key Literature

• ENCODE Phase 3: ENCODE Project Consortium 2020 (Nature, ~2,000 citations) DOI: 10.1038/s41586-020-2493-4 — Source catalog for all downloadable genomic data.
• FAIR Principles: Wilkinson et al. 2016 (Scientific Data, ~5,000 citations) DOI: 10.1038/sdata.2016.18 — Findable, Accessible, Interoperable, Reusable data principles that ENCODE's download infrastructure supports.
• IDR Framework: Li et al. 2011 (Annals of Applied Statistics) DOI: 10.1214/11-AOAS466 — Irreproducible Discovery Rate method used for peak thresholding in ENCODE.
• ENCODE Blacklist: Amemiya et al. 2019 (Scientific Reports, ~1,400 citations) DOI: 10.1038/s41598-019-45839-z — Regions to exclude from downloaded peak files before analysis.

Related Skills

search-encode

track-experiments

data-provenance

quality-assessment

publication-trust

liftover-coordinates

batch-analysis

For the request: "$ARGUMENTS"