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Encode Toolkit

Created By
ammawla13 days ago
MCP server and Claude Plugin for a full ENCODE Project genomic data and analysis toolkit — search, download, track, and analyze functional genomics experiments Search ENCODE, cross-reference 14 databases, run 7 analysis pipelines, and generate publication-ready methods — all from natural language in Claude Code. Start from ENCODE but go everywhere: discover histone peaks, cross-reference with GWAS variants, check ClinVar pathogenicity, pull GTEx expression, analyze TF binding motifs from JASPAR, run pipelines, and generate publication-ready methods with full provenance — in one conversation.
Content

ENCODE Toolkit — Genomics Research Infrastructure for Claude

License: CC BY-NC-ND 4.0 Python 3.10+ Version Status Skills Tools Pipelines Databases Tests Coverage Security Claude Code Provenance PyPI version npm version smithery badge DOI

Search ENCODE, cross-reference 14 databases, run 7 analysis pipelines, and generate publication-ready methods — all from natural language in Claude Code.

Start from ENCODE but go everywhere: discover histone peaks, cross-reference with GWAS variants, check ClinVar pathogenicity, pull GTEx expression, analyze TF binding motifs from JASPAR, run pipelines, and generate publication-ready methods with full provenance — in one conversation.


Quick Start

claude mcp add encode -- uvx encode-toolkit

That's it. All 20 tools and 47 skills are now available in Claude Code.

Other installation methods

npx (Node.js)

npx encode-toolkit

Or in MCP client config: { "command": "npx", "args": ["encode-toolkit"] }

pip install

pip install encode-toolkit

Then use encode-toolkit as the command in any MCP client configuration:

{
  "mcpServers": {
    "encode": {
      "command": "encode-toolkit"
    }
  }
}

Claude Code — Plugin Install

For the full experience (20 tools + 47 skills), install as a Claude Code plugin:

claude plugin add /path/to/encode-toolkit

Or install from a marketplace:

/plugin install encode-toolkit
Claude Desktop

Add to your 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"]
    }
  }
}

No installation needed when using uvx. Just add the config and restart Claude.

VS Code / Copilot

Add to .vscode/mcp.json in your workspace:

{
  "mcp": {
    "servers": {
      "encode": {
        "command": "uvx",
        "args": ["encode-toolkit"]
      }
    }
  }
}
Cursor

Add to .cursor/mcp.json:

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

Add to .windsurf/mcp.json:

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

Connected Databases

ENCODE Toolkit integrates 14 databases through live API tools and guided skills.

DatabaseAccess MethodUse Case
ENCODE20 MCP tools (live API)ChIP-seq, ATAC-seq, RNA-seq, Hi-C, WGBS, CUT&RUN data
GTExREST API (skill)Tissue-specific gene expression across 54 tissues
ClinVarE-utilities (skill)Variant clinical significance and pathogenicity
GWAS CatalogREST API (skill)Trait-variant associations from genome-wide studies
JASPARREST API (skill)Transcription factor binding motif profiles
CellxGeneCensus API (skill)Single-cell expression atlas across tissues
gnomADGraphQL (skill)Population allele frequencies and gene constraint
EnsemblREST API (skill)VEP annotation, Regulatory Build, coordinate liftover
UCSC Genome BrowserREST API (skill)cCRE tracks, TF clusters, sequence retrieval
GEOE-utilities (skill)Complementary expression/epigenomic datasets
PubMedMCP serverLiterature search and citation
bioRxivMCP serverPreprint discovery
ClinicalTrials.govMCP serverClinical trial cross-reference
Open TargetsMCP serverDrug target identification

What You Can Ask Claude

Search and explore

  • "Find all histone ChIP-seq experiments for human pancreas tissue"
  • "What ATAC-seq data is available for mouse brain?"
  • "Search for RNA-seq on GM12878 cell line"
  • "What histone marks have ChIP-seq data for pancreas?"

Download and track

  • "Download all BED files from ENCSR133RZO to ~/data/encode"
  • "Track experiment ENCSR133RZO with its publications"
  • "Export citations for my tracked experiments as BibTeX"

Cross-reference databases

  • "What GWAS variants overlap islet enhancers?"
  • "Check ClinVar pathogenicity for rs7903146"
  • "Pull GTEx expression for TCF7L2 across tissues"
  • "Find JASPAR motifs for HNF4A binding sites"

Run pipelines

  • "Set up a ChIP-seq pipeline for my H3K27ac experiments"
  • "Run ATAC-seq analysis with ENCODE-standard QC thresholds"

Generate methods and provenance

  • "Log that I created filtered_peaks.bed from ENCSR133RZO using bedtools"
  • "Generate a methods section for my analysis with citations"
More example prompts

Experiment details

  • "Show me the full details for experiment ENCSR133RZO"
  • "What files are available for ENCSR133RZO?"
  • "List only the BED files from ENCSR133RZO"

Bulk downloads

  • "Download all FASTQs from human pancreas ChIP-seq to /data/fastqs"
  • "Get the IDR thresholded peaks from these experiments"
  • "Download the bigWig signal tracks for H3K27me3 in GRCh38"

Compatibility analysis

  • "Are experiments ENCSR133RZO and ENCSR000AKS compatible for combined analysis?"
  • "Compare these two ChIP-seq experiments"

Provenance chains

  • "Show me the provenance chain for my derived files"
  • "What files have I derived from ENCSR133RZO?"

The Problem

Using genomics databases today means:

  1. Navigate web portals, click through dozens of filters
  2. Manually find the right experiments and files across multiple databases
  3. Write custom scripts to batch download
  4. Lose track of which files came from where

With ENCODE Toolkit, just tell Claude what you need:

"Find all histone ChIP-seq data for human pancreas tissue"

Claude searches ENCODE, returns a structured table of 66 experiments with targets, replicates, and file counts. Downloads are organized by experiment with MD5 verification and full provenance tracking.


Available Tools (20)

Five core tools are shown below. The remaining 15 are collapsed for readability.

encode_search_experiments

Search ENCODE experiments with 20+ filters.

ParameterTypeDescription
assay_titlestringAssay type: "Histone ChIP-seq", "ATAC-seq", "RNA-seq", "Hi-C", etc.
organismstringSpecies (default: "Homo sapiens")
organstringOrgan: "pancreas", "brain", "liver", "heart", "kidney", etc.
biosample_typestring"tissue", "cell line", "primary cell", "organoid"
targetstringChIP target: "H3K27me3", "H3K4me3", "CTCF", etc.
biosample_term_namestringSpecific biosample: "GM12878", "HepG2", etc.
limitintMax results (default: 25)

encode_get_experiment

Get full details for a single experiment including all files, quality metrics, and audit info.

ParameterTypeDescription
accessionstringExperiment ID (e.g., "ENCSR133RZO")

encode_download_files

Download specific files by accession to a local directory.

ParameterTypeDescription
file_accessionslist[str]File IDs to download (e.g., ["ENCFF635JIA"])
download_dirstringLocal path to save files
organize_bystring"flat", "experiment", "format", "experiment_format"
verify_md5boolVerify file integrity (default: true)

encode_batch_download

Search + download in one step. Runs in preview mode by default.

ParameterTypeDescription
download_dirstringLocal path to save files
file_formatstringFile format to download
assay_titlestringAssay type filter
organstringOrgan filter
dry_runboolPreview only (default: true). Set false to download.

encode_track_experiment

Track an experiment locally with its publications, methods, and pipeline info.

ParameterTypeDescription
accessionstringExperiment ID to track
fetch_publicationsboolFetch associated publications (default: true)
fetch_pipelinesboolFetch pipeline/analysis info (default: true)
notesstringOptional notes to attach
Search and discovery tools (4)

encode_list_files

List files for a specific experiment with format/type filters.

ParameterTypeDescription
experiment_accessionstringExperiment ID
file_formatstring"fastq", "bam", "bed", "bigWig", "bigBed", etc.
output_typestring"reads", "peaks", "signal", "alignments", etc.
assemblystring"GRCh38", "mm10", etc.
preferred_defaultboolOnly return recommended files

encode_search_files

Search files across all experiments with combined experiment + file filters.

ParameterTypeDescription
file_formatstringFile format filter
assay_titlestringAssay type of parent experiment
organstringOrgan of parent experiment
targetstringChIP/CUT&RUN target
output_typestringOutput type filter
assemblystringGenome assembly

encode_get_metadata

List valid filter values for any parameter.

ParameterTypeDescription
metadata_typestring"assays", "organisms", "organs", "biosample_types", "file_formats", "output_types", "assemblies"

encode_get_facets

Get live counts from ENCODE showing what data exists for given filters.

ParameterTypeDescription
assay_titlestringPre-filter by assay
organismstringPre-filter by organism
organstringPre-filter by organ
File and credential tools (2)

encode_get_file_info

Get detailed metadata for a single file.

ParameterTypeDescription
accessionstringFile ID (e.g., "ENCFF635JIA")

encode_manage_credentials

Store, check, or clear ENCODE credentials for restricted data access.

ParameterTypeDescription
actionstring"store", "check", or "clear"
access_keystringENCODE access key (for "store")
secret_keystringENCODE secret key (for "store")
Tracking and provenance tools (4)

encode_list_tracked

List all experiments in your local tracker with metadata, publication counts, and derived file counts.

ParameterTypeDescription
assay_titlestringFilter by assay type
organismstringFilter by organism
organstringFilter by organ

encode_get_citations

Get publications for tracked experiments. Export as BibTeX or RIS for reference managers.

ParameterTypeDescription
accessionstringSpecific experiment (or all if omitted)
export_formatstring"json" (default), "bibtex", or "ris"

encode_compare_experiments

Analyze whether two experiments are compatible for combined analysis.

ParameterTypeDescription
accession1stringFirst experiment ID
accession2stringSecond experiment ID

encode_summarize_collection

Get grouped statistics of your tracked experiment collection.

ParameterTypeDescription
assay_titlestringFilter by assay type
organismstringFilter by organism
organstringFilter by organ
Provenance and export tools (4)

encode_log_derived_file

Log a file you created from ENCODE data for provenance tracking.

ParameterTypeDescription
file_pathstringPath to your derived file
source_accessionslist[str]ENCODE accessions this was derived from
descriptionstringWhat the file contains
tool_usedstringTool/software used
parametersstringCommand or parameters used

encode_get_provenance

View provenance chains from derived files back to source ENCODE data.

ParameterTypeDescription
file_pathstringGet provenance for a specific file
source_accessionstringList all files derived from an accession

encode_export_data

Export tracked experiments as a table (CSV, TSV, or JSON) for Excel, R, pandas.

ParameterTypeDescription
formatstring"csv" (default), "tsv", or "json"
assay_titlestringFilter by assay type

Link external references (PubMed, bioRxiv, ClinicalTrials, GEO) to tracked experiments.

ParameterTypeDescription
experiment_accessionstringENCODE experiment accession
reference_typestring"pmid", "doi", "nct_id", "preprint_doi", "geo_accession", "other"
reference_idstringThe identifier value

encode_get_references

Get external references linked to tracked experiments for cross-server workflows.

ParameterTypeDescription
experiment_accessionstringFilter by experiment (optional)
reference_typestringFilter by type (optional)

Authentication

Most ENCODE data is public and requires no authentication. Just install and use.

For restricted/unreleased data, ask Claude: "Store my ENCODE credentials"

Credentials are encrypted using your OS keyring (macOS Keychain, Linux Secret Service, Windows Credential Locker) and never stored in plaintext. Get your access keys from your ENCODE profile.


Plugin Skills (47)

When installed as a Claude Code plugin, ENCODE Toolkit includes 47 literature-backed workflow skills that guide Claude through complex genomics tasks. Each analysis skill includes evidence-based quality thresholds, assay-specific metrics, and citations to primary literature.

Core Skills

SkillDescription
setupInstall and configure the ENCODE Toolkit server
search-encodeSearch and explore ENCODE experiments and files
download-encodeDownload files with organization and verification
track-experimentsTrack experiments, citations, and provenance locally
cross-referenceConnect ENCODE data to PubMed, bioRxiv, ClinicalTrials.gov
Analysis skills (9)
SkillDescription
quality-assessmentEvaluate experiment quality using ENCODE metrics — assay-specific thresholds for ChIP-seq (FRiP, NSC, RSC, NRF, IDR), ATAC-seq (TSS enrichment, NFR ratio), RNA-seq (mapping rate, gene body coverage), WGBS (bisulfite conversion, CpG coverage), Hi-C (cis/trans ratio), and CUT&RUN/CUT&Tag. Backed by Landt 2012, Buenrostro 2013, ENCODE Phase 3 (2020), Li 2011
integrative-analysisCombine multiple experiments with batch effect awareness — integration strategies (peak overlap, signal correlation, DiffBind, DESeq2, ChromHMM, ABC model). Backed by Ernst & Kellis 2012, Ross-Innes 2012, Love 2014, Fulco 2019
regulatory-elementsDiscover enhancers, promoters, insulators from combinatorial histone marks — ENCODE cCRE classification (926,535 elements), ChromHMM state interpretation. Backed by ENCODE Phase 3 (2020), Roadmap Epigenomics (2015), Whyte 2013
epigenome-profilingBuild comprehensive chromatin state profiles — three-tiered histone panels, ChromHMM 15-state model, bivalent chromatin analysis. References the chromatin biology catalog
compare-biosamplesCompare experiments across tissues and cell types — biosample hierarchy, tissue-specific regulation, batch effect detection. Backed by Roadmap Epigenomics (2015), Leek 2010
visualization-workflowGenerate publication-quality visualizations: genome browser tracks, heatmaps, and signal profiles
motif-analysisDiscover and analyze TF binding motifs in regulatory regions using HOMER, MEME, and JASPAR
peak-annotationAnnotate genomic peaks with features (promoter/enhancer/intergenic), nearest genes, and functional categories
batch-analysisBatch processing and QC screening across multiple ENCODE experiments with systematic quality filtering
Functional genomics skills (1)
SkillDescription
functional-screen-analysisAnalyze CRISPR screens, MPRA, and STARR-seq data from ENCODE — MAGeCK, BAGEL2, MPRAflow integration
Data aggregation skills (4)
SkillDescription
histone-aggregationUnion merge of histone ChIP-seq peaks across studies — signalValue-based noise filtering, sample-of-origin tagging, ENCODE blacklist removal. Backed by ChIP-Atlas (Oki 2018), Amemiya 2019, Perna 2024
accessibility-aggregationUnion merge of ATAC-seq and DNase-seq peaks — cross-platform integration, peak summit preservation. Backed by Corces 2017, Amemiya 2019, Zhao 2020
hic-aggregationUnion catalog of Hi-C chromatin loops (BEDPE) — resolution-aware anchor matching, loop caller concordance tracking. Backed by Loop Catalog (Reyna 2025), Mustache (Roayaei Ardakany 2020)
methylation-aggregationAggregate WGBS methylation profiles — per-CpG weighted averaging, HMR/UMR/PMD identification. Backed by Schultz 2015, DMRcate (Peters 2021), Zhou 2020
Multi-omics and meta-analysis skills (2)
SkillDescription
scrna-meta-analysisCross-study meta-analysis of scRNA-seq data — reproducibility assessment, TIN-based quality filtering, ambient RNA quantification. Backed by Tran 2020, Luecken & Theis 2019, Stuart 2019, Korsunsky 2019
multi-omics-integrationIntegrate RNA-seq, ATAC-seq, Histone ChIP-seq, and TF ChIP-seq — ABC model regulatory predictions, signal correlation. Backed by Fulco 2019, Corces 2018, ENCODE Phase 3 (2020)
Workflow skills (7)
SkillDescription
data-provenanceFull reproducibility tracking — tool versions, reference files, scripts, exact commands, timestamps, source-to-derived provenance chains
cite-encodeGenerate proper citations, BibTeX/RIS export, data availability statements
variant-annotationAnnotate GWAS/disease variants with ENCODE functional data — variant-to-gene mapping via cCREs. Backed by Finucane 2015, Maurano 2012
pipeline-guideUnderstand ENCODE uniform analysis pipelines and output types — pipeline specifications, Nextflow integration
single-cell-encodeWork with scRNA-seq and scATAC-seq data — platform comparison, cross-study integration, WNN multimodal analysis. Backed by Hao 2021, Stuart 2019
disease-researchDisease-focused workflows — GWAS variant interpretation, disease-tissue mapping, heritability enrichment, drug target identification via Open Targets. Backed by Buniello 2019, Finucane 2015
publication-trustPublication integrity assessment — 5-level trust scoring, retraction/erratum detection, citation analysis. Integrates with PubMed, bioRxiv, and Consensus
bioinformatics-installerInstall all bioinformatics tools for ENCODE analyses — 7 conda environment YAMLs, 3 install scripts, 134+ tools across ChIP-seq, ATAC-seq, RNA-seq, WGBS, Hi-C, DNase-seq, CUT&RUN
scientific-writingGenerate publication-ready methods sections, figure legends, supplementary tables, and data availability statements with full tool citations
liftover-coordinatesConvert genomic coordinates between assembly versions (hg19/hg38, mm9/mm10) using UCSC liftOver, CrossMap, Ensembl REST API, and rtracklayer
External database skills (9)
SkillDescription
gtex-expressionQuery GTEx tissue expression data via REST API for gene expression context across 54 tissues
clinvar-annotationAnnotate variants with ClinVar clinical significance, pathogenicity, and review status
cellxgene-contextQuery CellxGene single-cell atlas for cell type expression context across tissues
gwas-catalogSearch NHGRI-EBI GWAS Catalog for trait associations, risk alleles, and study metadata
jaspar-motifsQuery JASPAR database for transcription factor binding motifs and matrix profiles
ensembl-annotationEnsembl VEP variant annotation, Regulatory Build, coordinate liftover, gene lookup via REST API
geo-connectorSearch NCBI GEO for complementary datasets, cross-reference with ENCODE, FTP downloads
gnomad-variantsgnomAD population allele frequencies, gene constraint (LOEUF/pLI), structural variants via GraphQL
ucsc-browserUCSC Genome Browser REST API for cCRE tracks, TF binding clusters, and sequence retrieval
Pipeline execution skills (7)
PipelineAssayAlignerCaller
pipeline-chipseqChIP-seqBWA-MEMMACS2 + IDR
pipeline-atacseqATAC-seqBowtie2MACS2 (Tn5-adjusted)
pipeline-rnaseqRNA-seqSTARRSEM + Kallisto
pipeline-wgbsWGBSBismarkMethylDackel
pipeline-hicHi-CBWAJuicer + HiCCUPS
pipeline-dnaseseqDNase-seqBWAHotspot2
pipeline-cutandrunCUT&RUNBowtie2SEACR

Each pipeline includes a SKILL.md overview, 5-stage reference files (preprocessing through QC), a complete Nextflow DSL2 pipeline, a Dockerfile, and deployment configurations for local, SLURM, GCP, and AWS.

Reference files
FileDescription
skills/histone-aggregation/references/histone-marks-reference.mdComprehensive chromatin biology catalog (1,442 lines) — 21 histone marks with writers/erasers/readers, 5 novel acylation marks, ChromHMM state models (5 to 51 states), TF co-binding patterns, chromatin remodeling complexes, DNA methylation-chromatin interplay, nucleosome dynamics, 3D genome organization, chromatin in disease. 74 primary references
skills/*/references/literature.md33 per-skill literature reference documents — ~250 papers cataloged with DOI, PMID, citation counts, and skill-relevant key findings

Why ENCODE Toolkit

Most genomics tools give you one thing. ENCODE Toolkit gives you the full research loop:

CapabilityENCODE ToolkitTypical MCP servers
Live database access20 tools across 14 databasesSingle database, read-only
Executable pipelines7 Nextflow DSL2 pipelines with Docker and cloud configsNone
Provenance trackingFull audit trail from source data to derived filesNone
Publication outputBibTeX/RIS citations, auto-generated methods sectionsNone
Literature backing100+ primary references with assay-specific QC thresholdsNone
Workflow skills47 guided skills covering search to publicationStatic documentation

Supported Assay Types

50+ assay types across 7 categories
CategoryAssays
Histone/ChromatinHistone ChIP-seq, TF ChIP-seq, ATAC-seq, DNase-seq, CUT&RUN, CUT&Tag, MNase-seq
TranscriptionRNA-seq, total RNA-seq, small RNA-seq, long read RNA-seq, CAGE, RAMPAGE, PRO-seq, GRO-seq
3D GenomeHi-C, intact Hi-C, Micro-C, ChIA-PET, HiChIP, PLAC-seq, 5C
DNA MethylationWGBS, RRBS, MeDIP-seq, MRE-seq
FunctionalSTARR-seq, MPRA, CRISPR screen, eCLIP, iCLIP
Single CellscRNA-seq, snATAC-seq, 10x multiome, SHARE-seq, Parse SPLiT-seq
PerturbationCRISPRi + RNA-seq, shRNA + RNA-seq, siRNA + RNA-seq

Supported file formats: fastq bam bed bigWig bigBed tsv csv hic tagAlign bedpe pairs fasta vcf tar


Security and Privacy

  • 100% local execution — no telemetry, no analytics, no tracking
  • Credentials encrypted at rest via OS keyring with Fernet fallback
  • Certificate verification enforced — no verify=False
  • Rate limited to respect ENCODE's 10 req/sec policy
  • MD5 verification on all downloads by default
  • No data leaves your machine except queries to public APIs over HTTPS

Vignettes

Step-by-step walkthroughs showing real Claude sessions, including actual API output and scientific interpretation.

VignetteSkills Demonstrated
01 — Discovery & SearchFacets, search, metadata, quality-aware selection
02 — Download & TrackFile listing, download, tracking, citations, provenance
03 — Epigenomics WorkflowHistone marks, ATAC-seq, aggregation skills
04 — Variant & Disease ResearchGWAS catalog, ClinVar, GTEx, JASPAR, gnomAD
05 — Expression & Single-CellRNA-seq, scRNA-seq, GTEx, CellxGene, meta-analysis
06 — Motif & Regulatory AnalysisTF ChIP-seq, chromatin states, HOMER/MEME
07 — 3D Genome & MethylationHi-C loops, WGBS methylation, integrative analysis
08 — Pipeline ExecutionChIP-seq/ATAC-seq/RNA-seq pipelines, Nextflow
09 — Cross-Reference & IntegrationGEO, PubMed, Ensembl, UCSC, multi-omics
Individual skill vignettes

Every skill has a dedicated vignette in docs/skill-vignettes/ with a complete example session. Highlights:

SkillVignette Scenario
data-provenanceDownload, blacklist-filter, liftover, auto-generate methods section
histone-aggregationUnion merge of H3K27ac across 5 pancreas experiments
variant-annotationrs7903146 in TCF7L2 with islet enhancer evidence scoring
pipeline-chipseqFull Nextflow pipeline execution with ENCODE QC thresholds
gwas-catalogT2D GWAS variants overlaid on islet H3K27ac enhancers
publication-trustTrust assessment of artemisinin transdifferentiation claim
scrna-meta-analysis3-study islet integration following Mawla et al. 2019 framework

See the full showcase for 15 detailed examples.


Development

git clone https://github.com/ammawla/encode-toolkit.git
cd encode-toolkit
python -m venv .venv
source .venv/bin/activate
pip install -e ".[dev]"

Run the server locally:

encode-toolkit

Run tests:

pytest

Troubleshooting

"Server not found" in Claude Desktop
  • Make sure you restarted Claude Desktop after adding the config
  • Verify uvx is installed: pip install uv or curl -LsSf https://astral.sh/uv/install.sh | sh
"Connection refused" or timeout errors
  • Check your internet connection
  • ENCODE API rate limit is 10 requests/sec — the server handles this automatically
Downloads fail with 403
  • The file may require authentication. Ask Claude: "Store my ENCODE credentials"
  • Or check if the file status is "released" on encodeproject.org
No results for a search
  • Try broader filters (remove biosample_type or organ)
  • Use encode_get_facets to see what data actually exists for your filters
  • Use encode_get_metadata to check valid filter values

Author

Dr. Alex M. Mawla, PhD

License

Restrictive Non-Commercial License. Free for personal, educational, and academic research. No derivative works without written permission. Commercial use requires a separate license. See LICENSE for full terms.

For commercial licensing inquiries: ammawla@ucdavis.edu

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