nestkg

NeST KG

The NeST (Nested Systems in Tumors) Knowledge Graph converts the NeST hierarchical map of cancer protein systems into RDF, together with the IAS (Integrated Association Stringency) protein-association network from which the map was derived. It captures the nested containment hierarchy of protein systems, their member proteins, per-system cancer-mutation statistics and MONDO-typed cancer associations, and ~210k scored protein-protein associations as reified statements.

1.3M triples

12 classes

36 properties

227.8K subjects

Overview Example Queries Endpoints Schema

The NeST (Nested Systems in Tumors) Knowledge Graph (NeST KG) is a semantic knowledge graph derived from the NeST hierarchical map of human cancer protein systems. NeST organizes proteins into a nested hierarchy of physical assemblies and functional systems, inferred from integration of large-scale protein-protein interaction and cancer proteomics data.

The knowledge graph is constructed by converting the NeST networks from the Cytoscape CX2 format into RDF (Resource Description Framework) using standard biological ontologies. The source networks are publicly available on NDEx (Network Data Exchange).

Key Features

Nested System Hierarchy: Captures the containment relationships between protein systems, representing how smaller assemblies nest within larger functional systems
System Membership: Associates proteins (identified by UniProt accessions, or numeric HGNC identifiers for the 12 symbols with no protein product) with the systems they belong to
System Annotations: Every system carries its size (ndexv:memberCount) and HiSig significance statistics (lasso weight, BH-adjusted p-value); systems significantly mutated in a cohort additionally carry cancer associations with a tumors-mutated fraction
Standard Ontologies: Uses Biolink Model predicates for containment (biolink:part_of), system membership (biolink:has_member) and protein association (biolink:interacts_with), together with Biolink's Association pattern for system–cancer links; Semanticscience Integrated Ontology (SIO) for entity typing; and MONDO and ECO for cancer types and evidence codes.
Querying: biolink:interacts_with is symmetric but stored in one direction only — match both (?a ^biolink:interacts_with|biolink:interacts_with ?b). Per-edge IAS scores live on reified rdf:Statement nodes, not on the asserted triple.

Ontologies Used

Prefix	Ontology	Usage
biolink	Biolink Model	Containment (`part_of`), system membership (`has_member`), protein associations (`interacts_with`), and association structure (`Association`, `genetically_associated_with`, `knowledge_level`, `agent_type`, `has_evidence`)
SIO	Semanticscience Integrated Ontology	Entity types — `SIO:010043` (protein), `SIO:010035` (gene)
UniProt	UniProt	Protein entity identifiers
HGNC	HGNC	Gene entity identifiers — the 12 symbols with no protein product
MONDO	Mondo Disease Ontology	Cancer types in system→disease associations (14 types, incl. pan-cancer `MONDO:0004992`)
ECO	Evidence & Conclusion Ontology	Evidence code on each association
STATO, OBI, NCIT	—	Referenced via `rdfs:seeAlso` on the statistical properties
ndexv, nestv, iasv	Minted (NDEx)	`ndexv:ProteinSystem`, `ndexv:memberCount`, HiSig weight/p-value, IAS score

Funding

This work is supported by the NSF Proto-OKN (Prototype Open Knowledge Network) program, the NIH NCI NDEx project (5U24CA269436), and the NIH NHGRI Cytoscape project (5U24HG012107).

References

Zheng F, Kelly MR, Ramms DJ, Heintschel ML, Tao K, Tutuncuoglu B, Lee JJ, Ono K, Foussard H, Chen M, Herrington KA, Silva E, Liu SN, Chen J, Churas C, Wilson N, Kratz A, Pillich RT, Patel DN, Park J, Kuenzi B, Yu MK, Licon K, Pratt D, Kreisberg JF, Kim M, Swaney DL, Nan X, Fraley SI, Gutkind JS, Krogan NJ, Ideker T. Interpretation of cancer mutations using a multiscale map of protein systems. Science. 2021 Oct;374(6563):eabf3067. doi: 10.1126/science.abf3067. PMID: 34591613; PMCID: PMC8590742.

Pratt D, Chen J, Welker D, Rivas R, Pillich R, Rynkov V, Ono K, Miello C, Hicks L, Szalma S, Stojmirovic A, Dobrin R, Braxenthaler M, Kuentzer J, Demchak B, Ideker T. NDEx, the Network Data Exchange. Cell Syst. 2015 Oct 28;1(4):302-305. doi: 10.1016/j.cels.2015.10.001. PMID: 26594663; PMCID: PMC4649937.

Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003 Nov;13(11):2498-504. doi: 10.1101/gr.1239303. PMID: 14597658; PMCID: PMC403769.

Ono K, Fong D, Gao C, Churas C, Pillich R, Lenkiewicz J, Pratt D, Pico AR, Hanspers K, Xin Y, Morris J, Kucera M, Franz M, Lopes C, Bader G, Ideker T, Chen J. Cytoscape Web: bringing network biology to the browser. Nucleic Acids Res. 2025 Jul 7;53(W1):W203-W212. doi: 10.1093/nar/gkaf365. PMID: 40308211; PMCID: PMC12230733.

NeST systems significantly enriched for somatic mutation (HiSig adjusted p < 0.05)

PREFIX ndexv: <https://www.ndexbio.org/vocab/>
PREFIX nestv: <https://www.ndexbio.org/vocab/nest/>
PREFIX rdfs: <http://www.w3.org/2000/01/rdf-schema#>

SELECT ?system ?label ?adjP ?weight ?members WHERE {
  ?system a ndexv:ProteinSystem ;
          rdfs:label ?label ;
          ndexv:memberCount ?members ;
          nestv:hisigAdjustedPValue ?adjP .
  OPTIONAL { ?system nestv:hisigWeight ?weight }
  FILTER(?adjP < 0.05)
}
ORDER BY ?adjP
LIMIT 100

graph TD
classDef projected fill:lightgreen;
classDef literal fill:orange;
classDef iri fill:yellow;
  v1("?adjP"):::projected 
  v3("?label"):::projected 
  v4("?members"):::projected 
  v2("?system"):::projected 
  v5("?weight"):::projected 
  c3([https://www.ndexbio.org/vocab/ProteinSystem]):::iri 
  f0[["?adjP < '0.05^^xsd:decimal'"]]
  f0 --> v1
  v2 --"a"-->  c3
  v2 --"rdfs:label"-->  v3
  v2 --"https://www.ndexbio.org/vocab/memberCount"-->  v4
  v2 --"https://www.ndexbio.org/vocab/nest/hisigAdjustedPValue"-->  v1
  subgraph optional0["(optional)"]
  style optional0 fill:#bbf,stroke-dasharray: 5 5;
    v2 -."https://www.ndexbio.org/vocab/nest/hisigWeight".->  v5
  end

Run in OKN

Direct child subsystems of a given NeST system (one level down the hierarchy)

PREFIX ndexv: <https://www.ndexbio.org/vocab/>
PREFIX biolink: <https://w3id.org/biolink/vocab/>
PREFIX rdfs: <http://www.w3.org/2000/01/rdf-schema#>
PREFIX nest: <https://www.ndexbio.org/identifiers/>

SELECT ?child ?childLabel ?members WHERE {
  ?child biolink:part_of nest:NEST-1 ;
         rdfs:label ?childLabel ;
         ndexv:memberCount ?members .
}
ORDER BY DESC(?members)
LIMIT 100

graph TD
classDef projected fill:lightgreen;
classDef literal fill:orange;
classDef iri fill:yellow;
  v2("?child"):::projected 
  v3("?childLabel"):::projected 
  v1("?members"):::projected 
  c2([https://www.ndexbio.org/identifiers/NEST-1]):::iri 
  v2 --"biolink:part_of"-->  c2
  v2 --"rdfs:label"-->  v3
  v2 --"https://www.ndexbio.org/vocab/memberCount"-->  v1

Run in OKN

All NeST systems a given protein belongs to, with mutation-enrichment status, keyed on UniProt

PREFIX ndexv: <https://www.ndexbio.org/vocab/>
PREFIX nestv: <https://www.ndexbio.org/vocab/nest/>
PREFIX biolink: <https://w3id.org/biolink/vocab/>
PREFIX rdfs: <http://www.w3.org/2000/01/rdf-schema#>
PREFIX uniprot: <http://purl.uniprot.org/uniprot/>

# Example protein: EGFR = uniprot:P00533. Swap in any UniProt accession.
SELECT ?system ?label ?adjP (IF(?adjP < 0.05, "enriched", "not enriched") AS ?mutationStatus) WHERE {
  ?system biolink:has_member uniprot:P00533 ;
          rdfs:label ?label ;
          nestv:hisigAdjustedPValue ?adjP .
}
ORDER BY ?adjP
LIMIT 100

graph TD
classDef projected fill:lightgreen;
classDef literal fill:orange;
classDef iri fill:yellow;
  v1("?adjP"):::projected 
  v3("?label"):::projected 
  v4("?mutationStatus")
  v2("?system"):::projected 
  c2([uniprotkb:P00533]):::iri 
  v2 --"biolink:has_member"-->  c2
  v2 --"rdfs:label"-->  v3
  v2 --"https://www.ndexbio.org/vocab/nest/hisigAdjustedPValue"-->  v1
  bind0[/"if(?adjP < '0.05^^xsd:decimal','enriched','not enriched')"/]
  v1 --o bind0
  bind0 --as--o v4

Run in OKN

SPARQL Endpoint	`https://apps.okn.us/nestkg/sparql`
Triple Pattern Fragments	`https://apps.okn.us/ldf/nestkg`

Open in OKN Query UI

Classes (12) Properties (36)

Class	Entities

Property	Triples