# ProKN Knowledge Graph — Chat Transcript

👤 **User**
Give an overview of the @prokn KG

---

🧠 **Assistant**

Here's a comprehensive overview of the **ProKN (Protein Knowledge Network)** knowledge graph:

### ProKN — Protein Knowledge Network

**What it is:** ProKN is a protein-centric integrative knowledge graph developed by the University of Delaware as part of the NIH Common Fund Data Ecosystem (CFDE). It harmonizes heterogeneous biological data around proteins, connecting them to genes, diseases, pathways, post-translational modifications (PTMs), genetic variants, and drug interactions.

**Core focus areas:**

*Protein biology (UniProt backbone):* The graph is anchored to UniProt reviewed (Swiss-Prot) entries, carrying rich annotations including amino acid sequences, EC numbers, subcellular locations, organism/taxon links, PTM annotations, and natural variant annotations.

*Post-translational modifications:* A key specialty — ProKN tracks which kinases phosphorylate which proteins and how those modifications up- or down-regulate activity. The `KSMoFinder` tool (linked from the portal) predicts kinase-substrate interactions.

*Genetic variants:* Natural variant annotations are linked to associated diseases and phenotypes (via EFO), enabling variant-to-disease queries.

*Functional genomics:* Gene Ontology (GO) terms covering biological process, molecular function, and cellular component are fully integrated. GTEx expression data annotates genes with marker expression in heart, kidney, and liver tissue.

*Drug/disease connections:* Drugs and chemicals (from NCIT, BioAssay Ontology, schema.org) are linked to proteins via molecular interaction, inhibition, and treatment relations. Diseases connect through both UniProt annotations and the Biolink model.

**Ontologies and vocabularies used:** UniProt core, Biolink model, Gene Ontology (OBO), UBERON, Sequence Ontology, NCIT, BioAssay Ontology (BAO), MeSH, EFO, AOP ontology, CHEMINF, and schema.org — making ProKN one of the most ontologically diverse graphs in the Proto-OKN ecosystem.

**Identifier namespaces:** UniProt accessions, PubMed IDs, NCIT codes, SMILES, InChIKey, NCBI Taxon IDs, and EC numbers.

**Access:** SPARQL endpoint at `https://apps.okn.us/prokn/sparql`, plus a portal at [research.bioinformatics.udel.edu/ProKN](https://research.bioinformatics.udel.edu/ProKN/) with REST APIs, ID mapping, variant mapping, and protein embedding tools.

**Example queries you can run:**
- Find all properties and relationships for a specific gene like APOE
- Find all protein kinases
- Retrieve proteins associated with a specific disease

ProKN is well-suited for precision medicine and drug discovery research, particularly for bridging disparate CFDE datasets through its protein-centric integration layer.

---

👤 **User**
Visualize schema

---

🧠 **Assistant**

The ProKN schema is shown below as a Mermaid class diagram. Key things to note:

- `Protein` is the most connected node — it links to sequences, annotations, PTMs, GO terms, pathways, drugs, diseases, and variants.
- `PTMAnnotation` acts as a bidirectional hub — proteins phosphorylate it, and it in turn up/down-regulates protein activity.
- `GOTerm` aggregates many functional relationships from `Protein` (enables, involved in, colocalizes with, etc.).
- `GTExExpression` carries quantitative properties (`log2Ratio`, `deltaLog2Ratio`) and connects back to `Gene`.
- `Drug` has a self-referential `similar to` edge for chemical similarity queries.

```mermaid
classDiagram
direction TB

class Protein {
    string mnemonic
    string sequence
    int length
    string md5Checksum
    string version
    string activity
    string domain
    string annotation
    string ecNumber
    string geneSymbol
    string geneName
    string accessionNumber
    string aminoAcidVariation
}

class Gene {
    string geneIdentifier
}

class Taxon {
    string scientificName
    string taxonID
}

class Disease

class Pathway

class Annotation {
    string category
}

class Sequence {
    int length
    string md5Checksum
}

class Citation {
    string pmid
}

class Enzyme

class SubcellularLocation

class StructureResource

class PTMAnnotation {
    string modification
    string featureType
    string accessionNumber
    string position
}

class NaturalVariantAnnotation {
    string position
    string varioTerm
}

class BiologicalProcess

class MolecularActivity

class CellularComponent

class SequenceVariant

class AnatomicalEntity

class Cell

class ChemicalEntity

class Assay

class GOTerm {
    string hasAlternativeId
    string hasExactSynonym
    string hasOBONamespace
    string comment
    string label
}

class GTExExpression {
    float log2Ratio
    float deltaLog2Ratio
}

class Drug {
    string inchiKey
    string smiles
    string name
}

class Phenotype

class Bioassay

class SequenceFeature

class Experiment {
    string inchiKey
    string smiles
}

Gene --> Protein : gene product of
Protein --> Taxon : organism
Protein --> Sequence : sequence
Protein --> Annotation : annotation
Protein --> PTMAnnotation : phosphorylates
Protein --> PTMAnnotation : catalyzes
Protein --> NaturalVariantAnnotation : has sequence variant
Protein --> GOTerm : enables
Protein --> GOTerm : involved in
Protein --> GOTerm : acts upstream of
Protein --> GOTerm : colocalizes with
Protein --> GOTerm : is active in
Protein --> GOTerm : contributes to
Protein --> GOTerm : acts upstream of or within
Protein --> BiologicalProcess : acts upstream of positive effect
Protein --> BiologicalProcess : acts upstream of negative effect
Protein --> Pathway : participates in
Protein --> Drug : interacts with
PTMAnnotation --> Protein : up-regulates activity
PTMAnnotation --> Protein : down-regulates activity
Gene --> Disease : associated with
Gene --> Phenotype : associated with
Protein --> Disease : associated with
Protein --> Phenotype : associated with
NaturalVariantAnnotation --> Disease : causally related to
NaturalVariantAnnotation --> ChemicalEntity : causally related to
GTExExpression --> Gene : encodes
Cell --> Gene : has marker gene in heart
Cell --> Gene : has marker gene in kidney
Cell --> Gene : has marker gene in liver
AnatomicalEntity --> Gene : has marker gene in heart
AnatomicalEntity --> Gene : has marker gene in kidney
AnatomicalEntity --> Gene : has marker gene in liver
Drug --> Disease : treats
Drug --> Phenotype : treats
Drug --> Gene : negatively regulates
Drug --> Gene : positively regulates
Drug --> Protein : interacts with
Drug --> Protein : molecularly interacts with
Drug --> Drug : similar to
Gene --> Drug : causally influences
Experiment --> SequenceFeature : affected by
Bioassay --> ChemicalEntity : participates in
ChemicalEntity --> Bioassay : participates in
```

---

*Created by [mcp-proto-okn](https://github.com/sbl-sdsc/mcp-proto-okn) 0.6.0 on 2026-03-16*

*Model: claude-sonnet-4-6*
