Interaction Databases

What the source does

• FilesystemNone observedNo reads or writes in the source
• NetworkNone observedNo outbound calls in the source
• ShellNone observedNo commands run in the source
• DependenciesPinnedNothing floats
• SecretsNone foundNo keys in source

Five audit layers

Gates applied: no behavioural pass.

Audit 0.4.1 · source sha c8c1fc3a2b13 · 19 Oct 2026Report an issue or request a re-scan

• PublisherGPTomics GitHub organizationOwner of the repository this skill is read from
• Source folderGPTomics/bioSkills/database-access/interaction-databasesThe exact folder we audited
• LicenceMITAs the repository states it
• Commit pinned for this verdictc8c1fc3a2b13A new audit runs when the source changes
• Repository statusArchivedLast push 65 days ago
• Sandboxed runNot runSkills are read, not executed; layer L4 is skipped

Its description: Query protein-protein and gene interaction databases (STRING, BioGRID, IntAct, SIGNOR, Reactome, HuRI, HuMAP, OmniPath, ConsensusPathDB, DIP). Use when building PPI networks, choosing between physical vs functional vs…

---
name: bio-interaction-databases
description: Query protein-protein and gene interaction databases (STRING, BioGRID, IntAct, SIGNOR, Reactome, HuRI, HuMAP, OmniPath, ConsensusPathDB, DIP). Use when building PPI networks, choosing between physical vs functional vs genetic interactions, signed/directed vs undirected, high-throughput vs curated, picking confidence thresholds, aggregating across resources, or navigating license constraints. Encodes the database decision matrix, STRING v12 channel semantics, OmniPath as meta-database, SIGNOR for signed signaling, and per-resource rate limits.
tool_type: python
primary_tool: requests
---

## Version Compatibility

Reference examples tested with: requests 2.31+, pandas 2.2+, networkx 3.2+; STRING v12.0, BioGRID 4.4+, IntAct (live), SIGNOR 3.0+, OmniPath (live)

Before using code patterns, verify installed versions match. If versions differ:
- Python: `pip show requests pandas networkx`
- API surface: confirm endpoint URLs match each resource's current docs

STRING URL is version-pinned (`version-12-0` as of 2024); older URLs (`version-11-5`) were deprecated 2023. The Cytoscape/Cytoscape.js ecosystem uses different version semantics; check the docs for the targeted version.

# Interaction Databases

**"Get protein-protein interactions for these genes"** -> The choice of database matters more than the choice of API. Different resources index different evidence (physical binding, functional association, genetic interaction, signed signaling), with different curation pipelines (manually curated vs high-throughput vs text-mined), different species coverage, and different licenses.

The decision matrix below is the postdoc-grade view: **what question is being asked, and which resource answers it best?**

- Python: `requests.get()` against REST endpoints; `pandas` for parsing; `networkx` for graphs
- R: `STRINGdb`, `OmnipathR` (mature Bioconductor clients)
- Web: STRING, BioGRID, IntAct, SIGNOR, OmniPath, ConsensusPathDB browsers

## Required Setup

```python
import requests
import pandas as pd
import networkx as nx
from io import StringIO

CALLER = 'bioskills-2026'  # STRING + OmniPath accept caller_identity for usage attribution
```

API key requirements:
- **BioGRID**: free key required (`https://webservice.thebiogrid.org/`)
- **STRING, IntAct, SIGNOR, OmniPath, Reactome**: no key

## Decision matrix: which resource for which question?

| Question | Best resource | Why |
|---|---|---|
| "Build a network around 10 genes" | STRING (medium confidence ~400) | Comprehensive; channels combinable; good viz integration |
| "Only physically interacting proteins" | IntAct or BioGRID physical | Curated physical interactions; PSI-MI standard |
| "Signed/directed signaling (phospho, ubiq, etc.)" | **SIGNOR** | Only major DB with mechanism types and direction |
| "Functional enrichment based on co-mentioned genes" | STRING functional (default) | Includes textmining channel |
| "Genetic interactions (synthetic lethality)" | BioGRID genetic | Largest curated genetic interaction set |
| "High-throughput Y2H interactome" | **HuRI** | Reference yeast-2-hybrid map of human |
| "Mass-spec-derived protein complexes" | **HuMAP v2** or BioPlex | AP-MS complex maps |
| "Curated pathways with interactions" | Reactome | Pathway-organized; gold standard for signaling |
| "Meta-database aggregating 100+ sources" | **OmniPath** | The modern "one-stop"; pre-aggregated |
| "Cross-species or non-human" | STRING | Species coverage broadest |
| "Bacterial interactome" | STRING bacterial | Limited curated alternatives |
| "Phosphorylation site-specific" | PhosphoSitePlus (commercial license) or SIGNOR | PSP has best PTM coverage but requires license |

**OmniPath** (Türei et al. 2021 *Mol Sys Biol* 17:e9923) deserves special mention: it aggregates >100 sources into a unified API with provenance tracking. For "give me all available interactions for X" workflows, OmniPath is the modern default.

## STRING (v12, channels, confidence)

STRING (Szklarczyk et al. 2023 *Nucleic Acids Res* 51:D638) aggregates evidence into a combined confidence score. The seven evidence **channels**:

| Channel | What it captures |
|---|---|
| `experiments` | Direct experimental evidence (BioGRID, IntAct, etc.) |
| `database` | Curated database (Reactome, KEGG) |
| `textmining` | Co-mention in PubMed |
| `coexpression` | Co-expression across conditions |
| `neighborhood` | Genomic neighborhood (prokaryotes mainly) |
| `fusion` | Gene fusion across species |
| `cooccurrence` | Phylogenetic profile co-occurrence |

The default `score` is the combined-evidence score (0-1000). Confidence tiers:

| Threshold | Tier | Use when |
|---|---|---|
| 150 | Low | Exploration; includes weak textmining |
| 400 | Medium | Default; balanced sensitivity/specificity |
| 700 | High | Publication-quality networks |
| 900 | Highest | Experimentally validated core only |

**Version pinning**: STRING URL is `https://version-12-0.string-db.org/api/...` as of 2024. Older `version-11-5` URLs were deprecated 2023 — code using them silently fails. Use the unversioned `https://string-db.org/api/...` to follow the current release, or pin to a specific version for reproducibility.

**`caller_identity`**: STRING requests all programmatic users pass `caller_identity=<app-name>` for usage attribution. The parameter helps STRING identify and contact heavy automated callers.

## BioGRID (physical + genetic, curated + HT)

BioGRID (Oughtred et al. 2021 *Protein Sci* 30:187) covers physical and genetic interactions across the broadest organism set of any major resource. Requires a **free API key** (`https://webservice.thebiogrid.org/`).

Key concepts:
- `EXPERIMENTAL_SYSTEM`: e.g. "Two-hybrid", "Affinity Capture-MS", "Synthetic Growth Defect"
- `THROUGHPUT`: "Low Throughput" vs "High Throughput" — the most important quality flag
- `EVIDENCE_TYPE`: physical vs genetic

For high-confidence physical interactions, filter to physical systems + Low 

Excerpt, first 6,000 characters of SKILL.md, verbatim from the audited commit. It is text from someone else’s repository, quoted so you can judge it before your agent reads it.

pip install requests pandas networkx
pip install omnipath              # OmniPath Python client (cleaner than raw REST)

git clone https://github.com/GPTomics/bioSkills
git -C bioSkills checkout c8c1fc3a2b13

Works in

1. 2026-10-19
   ✓SAFE B 89 / 100

   first audit · source c8c1fc3a2b13

Questions about Interaction Databases

• github.com/GPTomics/bioSkills/tree/main/database-access/interact — the audited source at commit c8c1fc3a2b13 and every finding aboveObserved · 19 Oct 2026

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