Setup

ENCODE Toolkit Setup

When to Use

• User needs help installing or configuring the ENCODE Toolkit MCP server
• User is getting connection errors or server startup failures
• User asks "how do I set up ENCODE?" or "install ENCODE toolkit"
• User needs to configure ENCODE credentials for restricted data access
• User wants to verify their ENCODE server connection is working
• User is setting up a new environment and needs the ENCODE plugin

Help the user set up the ENCODE Toolkit server. The server connects Claude to the ENCODE Project genomics database — the largest public catalog of functional genomic elements with 8,000+ experiments across 50+ assay types.

Installation

The ENCODE Toolkit server is installed via uvx (recommended) or pip:

For Claude Code (CLI)

claude mcp add encode -- uvx encode-toolkit

For Claude Desktop

Add to claude_desktop_config.json:

• macOS: ~/Library/Application Support/Claude/claude_desktop_config.json
• Windows: %APPDATA%\Claude\claude_desktop_config.json

{
  "mcpServers": {
    "encode": {
      "command": "uvx",
      "args": ["encode-toolkit"]
    }
  }
}

Then restart Claude Desktop.

For VS Code (Claude Extension)

Add to your VS Code settings.json (Ctrl/Cmd + Shift + P → "Preferences: Open Settings (JSON)"):

{
  "claude.mcpServers": {
    "encode": {
      "command": "uvx",
      "args": ["encode-toolkit"]
    }
  }
}

For Cursor

Add to .cursor/mcp.json in your project root:

{
  "mcpServers": {
    "encode": {
      "command": "uvx",
      "args": ["encode-toolkit"]
    }
  }
}

For Windsurf

Add to ~/.codeium/windsurf/mcp_config.json:

{
  "mcpServers": {
    "encode": {
      "command": "uvx",
      "args": ["encode-toolkit"]
    }
  }
}

Alternative: pip install

pip install encode-toolkit
encode-toolkit  # Run the server

---

Verify Installation

After setup, test the connection with these verification queries (run them in order):

Step 1: Check metadata access

Ask: "List available ENCODE assay types"

• This calls encode_get_metadata(metadata_type="assays")
• Expected: Returns 50+ assay types including ChIP-seq, ATAC-seq, RNA-seq, WGBS, Hi-C

Step 2: Test search

Ask: "Search for ATAC-seq experiments on human brain"

• This calls encode_search_experiments(assay_title="ATAC-seq", organ="brain", organism="Homo sapiens")
• Expected: Returns experiment accessions (ENCSR...) with assay, biosample, and status info

Step 3: Test facets

Ask: "What organs have the most ENCODE data?"

• This calls encode_get_facets(facet_field="organ")
• Expected: Returns organ counts showing brain, liver, heart, etc. ranked by experiment count

If all three work, your setup is complete.

---

Authentication

Most ENCODE data is public and needs no authentication. For restricted/unreleased data:

1. Get API credentials from https://www.encodeproject.org/profile/ (requires ENCODE account)
2. Store them:

   Ask: "Store my ENCODE credentials"
   → Calls encode_manage_credentials(action="store", access_key="...", secret_key="...")
   

3. Credentials are encrypted via the OS keyring (macOS Keychain, Windows Credential Manager, or Linux Secret Service)
4. To verify: encode_manage_credentials(action="status")
5. To remove: encode_manage_credentials(action="remove")

---

20 Available Tools

After setup, these tools are available:

Category	Tools	Purpose
Search	encode_search_experiments, encode_get_facets, encode_get_metadata	Find experiments, explore data landscape, get valid filter values
Experiment Details	encode_get_experiment, encode_compare_experiments	Get full experiment metadata, compare two experiments
Files	encode_search_files, encode_list_files, encode_get_file_info	Find files, list files for an experiment, get file details
Download	encode_download_files, encode_batch_download	Download individual or batch files with MD5 verification
Tracking	encode_track_experiment, encode_list_tracked, encode_get_tracking_summary	Local experiment tracking with SQLite
Provenance	encode_log_derived_file, encode_get_provenance	Log analysis outputs with full lineage
Citations	encode_get_citations, encode_link_reference	Publication data, cross-reference to PubMed/GEO
Credentials	encode_manage_credentials	Store/remove API credentials
Collection	encode_summarize_collection	Summarize tracked experiment portfolio

---

First-Run Walkthrough: Pancreatic Islet Epigenomics

This walkthrough demonstrates a complete workflow from installation to data exploration.

1. Explore what's available

"What ENCODE assay types are available for human pancreas?"
→ encode_get_facets(facet_field="assay_title", organ="pancreas", organism="Homo sapiens")

2. Find specific experiments

"Find all histone ChIP-seq experiments on human pancreas"
→ encode_search_experiments(assay_title="Histone ChIP-seq", organ="pancreas", organism="Homo sapiens")

3. Examine an experiment

"Get details for ENCSR123ABC"
→ encode_get_experiment(accession="ENCSR123ABC")

4. Find the right files

"List the preferred BED files for ENCSR123ABC"
→ encode_list_files(accession="ENCSR123ABC", file_format="bed", assembly="GRCh38")

5. Download data

"Download the IDR-thresholded peaks for ENCSR123ABC"
→ encode_download_files(accession="ENCSR123ABC", file_format="bed", output_type="IDR thresholded peaks")

6. Track your experiment

"Track ENCSR123ABC in my local database with note 'H3K27ac pancreatic islets'"
→ encode_track_experiment(accession="ENCSR123ABC", notes="H3K27ac pancreatic islets")

---

Cross-Database Integration

The ENCODE Toolkit works alongside other MCP servers and REST APIs:

Database	Access Method	What It Adds
PubMed	MCP server (search_articles)	Literature citations for ENCODE experiments
bioRxiv	MCP server (search_preprints)	Preprint discovery for latest research
ClinicalTrials.gov	MCP server (search_trials)	Clinical trial cross-reference
Open Targets	MCP server (query_open_targets_graphql)	Drug target identification
GTEx	REST API via skill	Tissue-specific expression context
ClinVar	REST API via skill	Clinical variant annotation
GWAS Catalog	REST API via skill	Trait-associated variant lookups
gnomAD	GraphQL via skill	Population allele frequencies
Ensembl	REST API via skill	VEP annotation, Regulatory Build
UCSC	REST API via skill	Genome browser tracks, cCRE data
GEO	E-utilities via skill	Complementary expression datasets
JASPAR	REST API via skill	TF binding motif databases
CellxGene	REST API via skill	Single-cell expression atlases

---

47 Expert Skills

Beyond the 20 tools, the ENCODE Toolkit includes 47 skills providing domain expertise:

• Core (5): setup, search-encode, download-encode, track-experiments, cross-reference
• Analysis (9): quality-assessment, integrative-analysis, regulatory-elements, epigenome-profiling, compare-biosamples, visualization-workflow, motif-analysis, peak-annotation, batch-analysis
• Pipelines (7): pipeline-chipseq, pipeline-atacseq, pipeline-rnaseq, pipeline-wgbs, pipeline-hic, pipeline-dnaseseq, pipeline-cutandrun
• External DBs (9): gtex-expression, clinvar-annotation, cellxgene-context, gwas-catalog, jaspar-motifs, ensembl-annotation, geo-connector, gnomad-variants, ucsc-browser
• Workflows (10): data-provenance, cite-encode, variant-annotation, pipeline-guide, single-cell-encode, disease-research, publication-trust, bioinformatics-installer, scientific-writing, liftover-coordinates
• Data Aggregation (4): histone-aggregation, accessibility-aggregation, hic-aggregation, methylation-aggregation
• Meta-Analysis (2): scrna-meta-analysis, multi-omics-integration
• Functional Genomics (1): functional-screen-analysis

---

Pitfalls & Troubleshooting

Problem	Cause	Fix
"Server not found"	Claude not restarted after config change	Restart Claude Desktop / reload Claude Code
"uvx not found"	uv not installed	curl -LsSf https://astral.sh/uv/install.sh | sh
Timeout errors	Slow connection or ENCODE API load	Retry; rate limit (10 req/sec) is handled automatically
403 on downloads	File requires authentication	encode_manage_credentials(action="store", ...)
No results returned	Filters too narrow	Broaden filters; use encode_get_facets to see available data
"Invalid accession"	Wrong format	Must be ENCSR/ENCFF/ENCBS format (e.g., ENCSR000AAA)
Empty facets	API connectivity issue	Check internet; try encode_get_metadata(metadata_type="assays")
Stale results	Cached data	Cache TTL is 1 hour; restart server to clear

---

Code Examples

1. Verify server connection with metadata query

encode_get_metadata(metadata_type="assays")

Expected output:

{
  "assays": ["ATAC-seq", "ChIP-seq", "CUT&RUN", "CUT&Tag", "DNase-seq", "Hi-C", "MPRA", "RNA-seq", "STARR-seq", "WGBS", "eCLIP", "scATAC-seq", "scRNA-seq"]
}

2. Test search functionality

encode_search_experiments(assay_title="ATAC-seq", organ="brain", organism="Homo sapiens", limit=3)

Expected output:

{
  "total": 32,
  "results": [
    {"accession": "ENCSR000AAA", "assay_title": "ATAC-seq", "biosample_summary": "brain", "status": "released"}
  ]
}

3. Test facet exploration

encode_get_facets(facet_field="organ", organism="Homo sapiens")

Expected output:

{
  "facets": {
    "organ": {"brain": 450, "blood": 380, "liver": 220, "heart": 180, "lung": 150}
  }
}

Related Skills

Skill	When to Use
search-encode	First skill to use after setup — find experiments by assay, tissue, target
download-encode	Download ENCODE files (BED, bigWig, FASTQ, BAM) after finding experiments
pipeline-guide	Set up Nextflow pipelines for processing raw ENCODE data
bioinformatics-installer	Install all bioinformatics tools needed for ENCODE analysis
cross-reference	Link ENCODE experiments to PubMed, GEO, ClinicalTrials.gov
quality-assessment	Evaluate data quality before analysis
publication-trust	Verify literature claims backing analytical decisions

---

Presenting Results

When reporting setup results:

• Connection status: Confirm the ENCODE Toolkit server is connected and responding. Report the server version if available
• Available tools: List the 20 available ENCODE tools grouped by function (search, download, track, cross-reference, credentials)
• Test query result: Run a simple validation query (e.g., encode_get_metadata(metadata_type="assays")) and confirm it returns results successfully
• Authentication status: Note whether credentials are configured (for restricted data) or that public data access requires no authentication
• Troubleshooting: If any issues were encountered during setup, summarize the problem and resolution
• Next steps: Suggest search-encode to find experiments, or encode_get_facets to explore what ENCODE data is available for their research area

For the request: "$ARGUMENTS"