Version Compatibility

Reference examples tested with: BioPython 1.83+, pandas 2.2+

Before using code patterns, verify installed versions match. If versions differ:

• Python: pip show <package> then help(module.function) to check signatures

If code throws ImportError, AttributeError, or TypeError, introspect the installed package and adapt the example to match the actual API rather than retrying.

Interaction Databases

Query protein-protein interaction (PPI) and gene interaction databases to build and analyze biological networks.

"Get protein interactions for a gene list" → Query PPI databases (STRING, BioGRID, IntAct) via REST APIs to retrieve interaction partners and confidence scores.

• Python: requests.get() against STRING/BioGRID REST endpoints + pandas for parsing

STRING API

Query Interactions

import requests
import pandas as pd
from io import StringIO

STRING_API = 'https://version-12-0.string-db.org/api'

def get_string_interactions(genes, species=9606, score_threshold=400):
    '''Fetch PPI from STRING. species: 9606=human, 10090=mouse, 7227=fly'''
    url = f'{STRING_API}/tsv/network'
    params = {
        'identifiers': '%0d'.join(genes),
        'species': species,
        'required_score': score_threshold,
        'caller_identity': 'bioskills'
    }
    response = requests.get(url, params=params)
    return pd.read_csv(StringIO(response.text), sep='\t')

genes = ['TP53', 'BRCA1', 'MDM2', 'ATM', 'CHEK2', 'CDK2']
interactions = get_string_interactions(genes, score_threshold=700)
interactions[['preferredName_A', 'preferredName_B', 'score']].head()

STRING Confidence Score Tiers

Use 700+ for publication-quality networks. Use 400 for exploratory analysis where recall matters.

Resolve Gene Identifiers

def resolve_string_ids(genes, species=9606):
    '''Map gene names to STRING identifiers'''
    url = f'{STRING_API}/tsv/get_string_ids'
    params = {'identifiers': '%0d'.join(genes), 'species': species, 'caller_identity': 'bioskills'}
    response = requests.get(url, params=params)
    return pd.read_csv(StringIO(response.text), sep='\t')

resolved = resolve_string_ids(['TP53', 'BRCA1', 'MDM2'])
resolved[['queryItem', 'preferredName', 'stringId', 'annotation']]

STRING Functional Enrichment

def get_string_enrichment(genes, species=9606):
    '''Get GO/KEGG enrichment for a gene set via STRING'''
    url = f'{STRING_API}/tsv/enrichment'
    params = {'identifiers': '%0d'.join(genes), 'species': species, 'caller_identity': 'bioskills'}
    response = requests.get(url, params=params)
    df = pd.read_csv(StringIO(response.text), sep='\t')
    return df.sort_values('fdr')

enrichment = get_string_enrichment(genes)
enrichment[enrichment['category'] == 'Process'][['term', 'description', 'fdr', 'number_of_genes']].head(10)

STRING Network Image

def get_string_image(genes, species=9606):
    '''Download STRING network image as PNG'''
    url = f'{STRING_API}/image/network'
    params = {'identifiers': '%0d'.join(genes), 'species': species, 'caller_identity': 'bioskills'}
    response = requests.get(url, params=params)
    with open('string_network.png', 'wb') as f:
        f.write(response.content)

get_string_image(genes)

BioGRID REST API

BIOGRID_API = 'https://webservice.thebiogrid.org/interactions/'

def get_biogrid_interactions(gene, access_key, taxon=9606):
    '''Fetch interactions from BioGRID. Requires free API key from thebiogrid.org'''
    params = {
        'accesskey': access_key,
        'format': 'json',
        'searchNames': True,
        'geneList': gene,
        'taxId': taxon,
        'includeInteractors': True,
        'max': 1000
    }
    response = requests.get(BIOGRID_API, params=params)
    data = response.json()
    rows = [{'gene_a': v['OFFICIAL_SYMBOL_A'], 'gene_b': v['OFFICIAL_SYMBOL_B'],
             'system': v['EXPERIMENTAL_SYSTEM'], 'pubmed': v['PUBMED_ID'],
             'throughput': v['THROUGHPUT']} for v in data.values()]
    return pd.DataFrame(rows)

# biogrid_df = get_biogrid_interactions('TP53', access_key='YOUR_KEY')

Filter BioGRID by Evidence

def filter_biogrid(df, systems=None, low_throughput_only=False):
    '''Filter BioGRID by experimental system or throughput'''
    if low_throughput_only:
        df = df[df['throughput'] == 'Low Throughput']
    if systems:
        df = df[df['system'].isin(systems)]
    return df

# High-confidence physical interactions
# physical_systems = ['Affinity Capture-MS', 'Two-hybrid', 'Co-crystal Structure',
#                     'Reconstituted Complex', 'Affinity Capture-Western']
# filtered = filter_biogrid(biogrid_df, systems=physical_systems, low_throughput_only=True)

IntAct / PSICQUIC

def query_intact(gene, species='human'):
    '''Query IntAct via PSICQUIC REST API'''
    url = f'https://www.ebi.ac.uk/intact/ws/interactors/findInteractor/{gene}'
    params = {'species': species}
    response = requests.get(url, params=params)
    return response.json()

def query_psicquic(query):
    '''Query IntAct PSICQUIC for MITAB-formatted interactions'''
    url = 'https://www.ebi.ac.uk/intact/ws/interactors/list/resolve'
    response = requests.post(url, json={'query': query})
    return response.json()

OmniPath

def get_omnipath_interactions(genes):
    '''Query OmniPath for curated signaling interactions'''
    url = 'https://omnipathdb.org/interactions'
    params = {'genesymbols': 1, 'fields': 'sources,references', 'partners': ','.join(genes)}
    response = requests.get(url, params=params)
    df = pd.read_csv(StringIO(response.text), sep='\t')
    return df

omni = get_omnipath_interactions(['TP53', 'MDM2', 'BRCA1'])
omni[['source_genesymbol', 'target_genesymbol', 'is_directed', 'is_stimulation', 'is_inhibition']].head()

OmniPath Endpoint Reference

Convert to NetworkX

Goal: Build an analyzable graph object from a STRING interactions table for network metrics and visualization.

Approach: Filter interactions by confidence score, then create a NetworkX graph with edge weights derived from STRING scores.

import networkx as nx

def string_to_networkx(interactions_df, score_col='score', min_score=700):
    '''Convert STRING interactions DataFrame to NetworkX graph'''
    filtered = interactions_df[interactions_df[score_col] >= min_score]
    G = nx.Graph()
    for _, row in filtered.iterrows():
        G.add_edge(row['preferredName_A'], row['preferredName_B'],
                   weight=row[score_col] / 1000, score=row[score_col])
    return G

G = string_to_networkx(interactions)
print(f'Network: {G.number_of_nodes()} nodes, {G.number_of_edges()} edges')

degree_df = pd.DataFrame(G.degree(), columns=['gene', 'degree']).sort_values('degree', ascending=False)
degree_df.head()

Multi-Database Aggregation

Goal: Combine protein interaction evidence from multiple databases into a single high-confidence network.

Approach: Normalize edge pairs from STRING and OmniPath into a common format, merge into one graph, and track which databases support each interaction.

def aggregate_interactions(string_df, omnipath_df):
    '''Combine interactions from multiple databases into a unified network'''
    edges = set()
    for _, row in string_df.iterrows():
        a, b = sorted([row['preferredName_A'], row['preferredName_B']])
        edges.add((a, b, 'STRING', row['score']))
    for _, row in omnipath_df.iterrows():
        a, b = row['source_genesymbol'], row['target_genesymbol']
        edges.add((a, b, 'OmniPath', 1000))

    G = nx.Graph()
    for a, b, source, score in edges:
        if G.has_edge(a, b):
            G[a][b]['sources'].append(source)
            G[a][b]['max_score'] = max(G[a][b]['max_score'], score)
        else:
            G.add_edge(a, b, sources=[source], max_score=score)
    return G

Network Statistics

def network_summary(G):
    '''Compute basic network statistics'''
    stats = {
        'nodes': G.number_of_nodes(),
        'edges': G.number_of_edges(),
        'density': nx.density(G),
        'components': nx.number_connected_components(G),
        'avg_clustering': nx.average_clustering(G),
    }
    if nx.is_connected(G):
        stats['diameter'] = nx.diameter(G)
        stats['avg_path_length'] = nx.average_shortest_path_length(G)
    return stats

network_summary(G)

Related Skills

• database-access/uniprot-access - Protein annotations and cross-references
• pathway-analysis/go-enrichment - Functional enrichment of network genes
• gene-regulatory-networks/coexpression-networks - Co-expression network construction
• data-visualization/network-visualization - Visualize interaction networks