STRING Database
Overview
STRING is a comprehensive database of known and predicted protein-protein interactions covering 59M proteins and 20B+ interactions across 5000+ organisms. Query interaction networks, perform functional enrichment, discover partners via REST API for systems biology and pathway analysis.
When to Use This Skill
This skill should be used when:
- Retrieving protein-protein interaction networks for single or multiple proteins
- Performing functional enrichment analysis (GO, KEGG, Pfam) on protein lists
- Discovering interaction partners and expanding protein networks
- Testing if proteins form significantly enriched functional modules
- Generating network visualizations with evidence-based coloring
- Analyzing homology and protein family relationships
- Conducting cross-species protein interaction comparisons
- Identifying hub proteins and network connectivity patterns
Quick Start
The skill provides:
- Python helper functions (
scripts/string_api.py) for all STRING REST API operations - Comprehensive reference documentation (
references/string_reference.md) with detailed API specifications
When users request STRING data, determine which operation is needed and use the appropriate function from scripts/string_api.py.
Core Operations
1. Identifier Mapping (string_map_ids)
Convert gene names, protein names, and external IDs to STRING identifiers.
When to use: Starting any STRING analysis, validating protein names, finding canonical identifiers.
Usage:
from scripts.string_api import string_map_ids
# Map single protein
result = string_map_ids('TP53', species=9606)
# Map multiple proteins
result = string_map_ids(['TP53', 'BRCA1', 'EGFR', 'MDM2'], species=9606)
# Map with multiple matches per query
result = string_map_ids('p53', species=9606, limit=5)Parameters:
species: NCBI taxon ID (9606 = human, 10090 = mouse, 7227 = fly)limit: Number of matches per identifier (default: 1)echo_query: Include query term in output (default: 1)
Best practice: Always map identifiers first for faster subsequent queries.
2. Network Retrieval (string_network)
Get protein-protein interaction network data in tabular format.
When to use: Building interaction networks, analyzing connectivity, retrieving interaction evidence.
Usage:
from scripts.string_api import string_network
# Get network for single protein
network = string_network('9606.ENSP00000269305', species=9606)
# Get network with multiple proteins
proteins = ['9606.ENSP00000269305', '9606.ENSP00000275493']
network = string_network(proteins, required_score=700)
# Expand network with additional interactors
network = string_network('TP53', species=9606, add_nodes=10, required_score=400)
# Physical interactions only
network = string_network('TP53', species=9606, network_type='physical')Parameters:
required_score: Confidence threshold (0-1000)
- 150: low confidence (exploratory) - 400: medium confidence (default, standard analysis) - 700: high confidence (conservative) - 900: highest confidence (very stringent)
network_type:'functional'(all evidence, default) or'physical'(direct binding only)add_nodes: Add N most connected proteins (0-10)
Output columns: Interaction pairs, confidence scores, and individual evidence scores (neighborhood, fusion, coexpression, experimental, database, text-mining).
3. Network Visualization (string_network_image)
Generate network visualization as PNG image.
When to use: Creating figures, visual exploration, presentations.
Usage:
from scripts.string_api import string_network_image
# Get network image
proteins = ['TP53', 'MDM2', 'ATM', 'CHEK2', 'BRCA1']
img_data = string_network_image(proteins, species=9606, required_score=700)
# Save image
with open('network.png', 'wb') as f:
f.write(img_data)
# Evidence-colored network
img = string_network_image(proteins, species=9606, network_flavor='evidence')
# Confidence-based visualization
img = string_network_image(proteins, species=9606, network_flavor='confidence')
# Actions network (activation/inhibition)
img = string_network_image(proteins, species=9606, network_flavor='actions')Network flavors:
'evidence': Colored lines show evidence types (default)'confidence': Line thickness represents confidence'actions': Shows activating/inhibiting relationships
4. Interaction Partners (string_interaction_partners)
Find all proteins that interact with given protein(s).
When to use: Discovering novel interactions, finding hub proteins, expanding networks.
Usage:
from scripts.string_api import string_interaction_partners
# Get top 10 interactors of TP53
partners = string_interaction_partners('TP53', species=9606, limit=10)
# Get high-confidence interactors
partners = string_interaction_partners('TP53', species=9606,
limit=20, required_score=700)
# Find interactors for multiple proteins
partners = string_interaction_partners(['TP53', 'MDM2'],
species=9606, limit=15)Parameters:
limit: Maximum number of partners to return (default: 10)required_score: Confidence threshold (0-1000)
Use cases:
- Hub protein identification
- Network expansion from seed proteins
- Discovering indirect connections
5. Functional Enrichment (string_enrichment)
Perform enrichment analysis across Gene Ontology, KEGG pathways, Pfam domains, and more.
When to use: Interpreting protein lists, pathway analysis, functional characterization, understanding biological processes.
Usage:
from scripts.string_enrichment import string_enrichment
# Enrichment for a protein list
proteins = ['TP53', 'MDM2', 'ATM', 'CHEK2', 'BRCA1', 'ATR', 'TP73']
enrichment = string_enrichment(proteins, species=9606)
# Parse results to find significant terms
import pandas as pd
df = pd.read_csv(io.StringIO(enrichment), sep='\t')
significant = df[df['fdr'] < 0.05]Enrichment categories:
- Gene Ontology: Biological Process, Molecular Function, Cellular Component
- KEGG Pathways: Metabolic and signaling pathways
- Pfam: Protein domains
- InterPro: Protein families and domains
- SMART: Domain architecture
- UniProt Keywords: Curated functional keywords
Output columns:
category: Annotation database (e.g., "KEGG Pathways", "GO Biological Process")term: Term identifierdescription: Human-readable term descriptionnumber_of_genes: Input proteins with this annotationp_value: Uncorrected enrichment p-valuefdr: False discovery rate (corrected p-value)
Statistical method: Fisher's exact test with Benjamini-Hochberg FDR correction.
Interpretation: FDR < 0.05 indicates statistically significant enrichment.
6. PPI Enrichment (string_ppi_enrichment)
Test if a protein network has significantly more interactions than expected by chance.
When to use: Validating if proteins form functional module, testing network connectivity.
Usage:
from scripts.string_api import string_ppi_enrichment
import json
# Test network connectivity
proteins = ['TP53', 'MDM2', 'ATM', 'CHEK2', 'BRCA1']
result = string_ppi_enrichment(proteins, species=9606, required_score=400)
# Parse JSON result
data = json.loads(result)
print(f"Observed edges: {data['number_of_edges']}")
print(f"Expected edges: {data['expected_number_of_edges']}")
print(f"P-value: {data['p_value']}")Output fields:
number_of_nodes: Proteins in networknumber_of_edges: Observed interactionsexpected_number_of_edges: Expected in random networkp_value: Statistical significance
Interpretation:
- p-value < 0.05: Network is significantly enriched (proteins likely form functional module)
- p-value ≥ 0.05: No significant enrichment (proteins may be unrelated)
7. Homology Scores (string_homology)
Retrieve protein similarity and homology information.
When to use: Identifying protein families, paralog analysis, cross-species comparisons.
Usage:
from scripts.string_api import string_homology
# Get homology between proteins
proteins = ['TP53', 'TP63', 'TP73'] # p53 family
homology = string_homology(proteins, species=9606)Use cases:
- Protein family identification
- Paralog discovery
- Evolutionary analysis
8. Version Information (string_version)
Get current STRING database version.
When to use: Ensuring reproducibility, documenting methods.
Usage:
from scripts.string_api import string_version
version = string_version()
print(f"STRING version: {version}")Common Analysis Workflows
Workflow 1: Protein List Analysis (Standard Workflow)
Use case: Analyze a list of proteins from experiment (e.g., differential expression, proteomics).
from scripts.string_api import (string_map_ids, string_network,
string_enrichment, string_ppi_enrichment,
string_network_image)
# Step 1: Map gene names to STRING IDs
gene_list = ['TP53', 'BRCA1', 'ATM', 'CHEK2', 'MDM2', 'ATR', 'BRCA2']
mapping = string_map_ids(gene_list, species=9606)
# Step 2: Get interaction network
network = string_network(gene_list, species=9606, required_score=400)
# Step 3: Test if network is enriched
ppi_result = string_ppi_enrichment(gene_list, species=9606)
# Step 4: Perform functional enrichment
enrichment = string_enrichment(gene_list, species=9606)
# Step 5: Generate network visualization
img = string_network_image(gene_list, species=9606,
network_flavor='evidence', required_score=400)
with open('protein_network.png', 'wb') as f:
f.write(img)
# Step 6: Parse and interpret resultsWorkflow 2: Single Protein Investigation
Use case: Deep dive into one protein's interactions and partners.
from scripts.string_api import (string_map_ids, string_interaction_partners,
string_network_image)
# Step 1: Map protein name
protein = 'TP53'
mapping = string_map_ids(protein, species=9606)
# Step 2: Get all interaction partners
partners = string_interaction_partners(protein, species=9606,
limit=20, required_score=700)
# Step 3: Visualize expanded network
img = string_network_image(protein, species=9606, add_nodes=15,
network_flavor='confidence', required_score=700)
with open('tp53_network.png', 'wb') as f:
f.write(img)Workflow 3: Pathway-Centric Analysis
Use case: Identify and visualize proteins in a specific biological pathway.
from scripts.string_api import string_enrichment, string_network
# Step 1: Start with known pathway proteins
dna_repair_proteins = ['TP53', 'ATM', 'ATR', 'CHEK1', 'CHEK2',
'BRCA1', 'BRCA2', 'RAD51', 'XRCC1']
# Step 2: Get network
network = string_network(dna_repair_proteins, species=9606,
required_score=700, add_nodes=5)
# Step 3: Enrichment to confirm pathway annotation
enrichment = string_enrichment(dna_repair_proteins, species=9606)
# Step 4: Parse enrichment for DNA repair pathways
import pandas as pd
import io
df = pd.read_csv(io.StringIO(enrichment), sep='\t')
dna_repair = df[df['description'].str.contains('DNA repair', case=False)]Workflow 4: Cross-Species Analysis
Use case: Compare protein interactions across different organisms.
from scripts.string_api import string_network
# Human network
human_network = string_network('TP53', species=9606, required_score=700)
# Mouse network
mouse_network = string_network('Trp53', species=10090, required_score=700)
# Yeast network (if ortholog exists)
yeast_network = string_network('gene_name', species=4932, required_score=700)Workflow 5: Network Expansion and Discovery
Use case: Start with seed proteins and discover connected functional modules.
from scripts.string_api import (string_interaction_partners, string_network,
string_enrichment)
# Step 1: Start with seed protein(s)
seed_proteins = ['TP53']
# Step 2: Get first-degree interactors
partners = string_interaction_partners(seed_proteins, species=9606,
limit=30, required_score=700)
# Step 3: Parse partners to get protein list
import pandas as pd
import io
df = pd.read_csv(io.StringIO(partners), sep='\t')
all_proteins = list(set(df['preferredName_A'].tolist() +
df['preferredName_B'].tolist()))
# Step 4: Perform enrichment on expanded network
enrichment = string_enrichment(all_proteins[:50], species=9606)
# Step 5: Filter for interesting functional modules
enrichment_df = pd.read_csv(io.StringIO(enrichment), sep='\t')
modules = enrichment_df[enrichment_df['fdr'] < 0.001]Common Species
When specifying species, use NCBI taxon IDs:
| Organism | Common Name | Taxon ID |
|---|---|---|
| Homo sapiens | Human | 9606 |
| Mus musculus | Mouse | 10090 |
| Rattus norvegicus | Rat | 10116 |
| Drosophila melanogaster | Fruit fly | 7227 |
| Caenorhabditis elegans | C. elegans | 6239 |
| Saccharomyces cerevisiae | Yeast | 4932 |
| Arabidopsis thaliana | Thale cress | 3702 |
| Escherichia coli | E. coli | 511145 |
| Danio rerio | Zebrafish | 7955 |
Full list available at: https://string-db.org/cgi/input?input_page_active_form=organisms
Understanding Confidence Scores
STRING provides combined confidence scores (0-1000) integrating multiple evidence types:
Evidence Channels
- Neighborhood (nscore): Conserved genomic neighborhood across species
- Fusion (fscore): Gene fusion events
- Phylogenetic Profile (pscore): Co-occurrence patterns across species
- Coexpression (ascore): Correlated RNA expression
- Experimental (escore): Biochemical and genetic experiments
- Database (dscore): Curated pathway and complex databases
- Text-mining (tscore): Literature co-occurrence and NLP extraction
Recommended Thresholds
Choose threshold based on analysis goals:
- 150 (low confidence): Exploratory analysis, hypothesis generation
- 400 (medium confidence): Standard analysis, balanced sensitivity/specificity
- 700 (high confidence): Conservative analysis, high-confidence interactions
- 900 (highest confidence): Very stringent, experimental evidence preferred
Trade-offs:
- Lower thresholds: More interactions (higher recall, more false positives)
- Higher thresholds: Fewer interactions (higher precision, more false negatives)
Network Types
Functional Networks (Default)
Includes all evidence types (experimental, computational, text-mining). Represents proteins that are functionally associated, even without direct physical binding.
When to use:
- Pathway analysis
- Functional enrichment studies
- Systems biology
- Most general analyses
Physical Networks
Only includes evidence for direct physical binding (experimental data and database annotations for physical interactions).
When to use:
- Structural biology studies
- Protein complex analysis
- Direct binding validation
- When physical contact is required
API Best Practices
- Always map identifiers first: Use
string_map_ids()before other operations for faster queries - Use STRING IDs when possible: Use format
9606.ENSP00000269305instead of gene names - Specify species for networks >10 proteins: Required for accurate results
- Respect rate limits: Wait 1 second between API calls
- Use versioned URLs for reproducibility: Available in reference documentation
- Handle errors gracefully: Check for "Error:" prefix in returned strings
- Choose appropriate confidence thresholds: Match threshold to analysis goals
Detailed Reference
For comprehensive API documentation, complete parameter lists, output formats, and advanced usage, refer to references/string_reference.md. This includes:
- Complete API endpoint specifications
- All supported output formats (TSV, JSON, XML, PSI-MI)
- Advanced features (bulk upload, values/ranks enrichment)
- Error handling and troubleshooting
- Integration with other tools (Cytoscape, R, Python libraries)
- Data license and citation information
Troubleshooting
No proteins found:
- Verify species parameter matches identifiers
- Try mapping identifiers first with
string_map_ids() - Check for typos in protein names
Empty network results:
- Lower confidence threshold (
required_score) - Check if proteins actually interact
- Verify species is correct
Timeout or slow queries:
- Reduce number of input proteins
- Use STRING IDs instead of gene names
- Split large queries into batches
"Species required" error:
- Add
speciesparameter for networks with >10 proteins - Always include species for consistency
Results look unexpected:
- Check STRING version with
string_version() - Verify network_type is appropriate (functional vs physical)
- Review confidence threshold selection
Additional Resources
For proteome-scale analysis or complete species network upload:
- Visit https://string-db.org
- Use "Upload proteome" feature
- STRING will generate complete interaction network and predict functions
For bulk downloads of complete datasets:
- Download page: https://string-db.org/cgi/download
- Includes complete interaction files, protein annotations, and pathway mappings
Data License
STRING data is freely available under Creative Commons BY 4.0 license:
- Free for academic and commercial use
- Attribution required when publishing
- Cite latest STRING publication
Citation
When using STRING in publications, cite the most recent publication from: https://string-db.org/cgi/about
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