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string
question
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category
string
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string
reasoning_type
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string
num_hops
int64
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list
gold_standard_path
string
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cq1
By what mechanism does Palovarotene treat Fibrodysplasia Ossificans Progressiva (FOP)?
Drug Mechanism of Action
Rare Disease (FOP)
multi_hop_traversal
intermediate
3
[ { "name": "Palovarotene", "curie": "CHEMBL:2105648", "type": "biolink:SmallMolecule", "role": "RAR-gamma agonist" }, { "name": "RARG", "curie": "HGNC:9866", "type": "biolink:Gene", "role": "Retinoic acid receptor gamma" }, { "name": "ACVR1", "curie": "HGNC:171", "type": "biolink:Gene", "role": "BMP receptor (causal gene)" }, { "name": "FOP", "curie": "MONDO:0007606", "type": "biolink:Disease", "role": "Target disease" } ]
Drug(Palovarotene) --[agonist]--> Protein(RARG) --[regulates]--> Protein(ACVR1) --[causes]--> Disease(FOP)
[ "Anchor: chembl_search_compounds('palovarotene') -> CHEMBL:2105648", "Enrich: chembl_get_compound('CHEMBL:2105648') -> Max Phase 4, indications", "Mechanism: ChEMBL /mechanism -> RARG agonist", "Target Gene: hgnc_get_gene('HGNC:171') -> ACVR1 details", "Disease Link: opentargets_get_associations('ENSG00000115170') -> FOP association", "Persist: graphiti add_memory(group_id='cq1-fop-mechanism')" ]
DrugMechDB
null
cq1-fop-mechanism
[ "ChEMBL", "HGNC", "Open Targets" ]
[ { "source": "CHEMBL:2105648", "target": "HGNC:9866", "predicate": "biolink:agonist_of" }, { "source": "HGNC:9866", "target": "HGNC:171", "predicate": "biolink:regulates" }, { "source": "HGNC:171", "target": "MONDO:0007606", "predicate": "biolink:gene_associated_with_condition" } ]
cq2
What other drugs targeting the BMP Signaling Pathway could be repurposed for FOP?
Drug Repurposing
Rare Disease (FOP)
multi_hop_traversal
advanced
4
[ { "name": "ACVR1", "curie": "HGNC:171", "type": "biolink:Gene", "role": "Causal gene" }, { "name": "BMP Signaling Pathway", "curie": "WP:WP2760", "type": "biolink:Pathway", "role": "Target pathway" }, { "name": "LDN-193189", "curie": "CHEMBL:405130", "type": "biolink:SmallMolecule", "role": "ACVR1/BMPR1A inhibitor" }, { "name": "Dorsomorphin", "curie": "CHEMBL:495727", "type": "biolink:SmallMolecule", "role": "BMP inhibitor" } ]
Gene(ACVR1) --[participates_in]--> Pathway(BMP) --[has_member]--> Gene(BMPR1A) --[target_of]--> Drug(LDN-193189)
[ "Anchor: hgnc_get_gene('HGNC:171') -> ACVR1", "Pathway Discovery: wikipathways_get_pathways_for_gene('ACVR1') -> BMP pathway", "Pathway Components: wikipathways_get_pathway_components('WP:WP2760') -> Member genes", "Drug Search: chembl_search_compounds('ACVR1 inhibitor') -> Candidates", "Persist: graphiti add_memory(group_id='cq2-fop-repurposing')" ]
DrugMechDB
null
cq2-fop-repurposing
[ "HGNC", "WikiPathways", "ChEMBL" ]
[ { "source": "HGNC:171", "target": "WP:WP2760", "predicate": "biolink:participates_in" }, { "source": "WP:WP2760", "target": "CHEMBL:405130", "predicate": "biolink:has_participant" } ]
cq3
What genes and proteins are implicated in Alzheimer's Disease progression, and how do they interact?
Gene-Protein Network
Neurodegeneration (Alzheimer's)
network_expansion
advanced
4
[ { "name": "APP", "curie": "HGNC:620", "type": "biolink:Gene", "role": "Amyloid precursor protein" }, { "name": "APOE", "curie": "HGNC:613", "type": "biolink:Gene", "role": "Apolipoprotein E (risk factor)" }, { "name": "PSEN1", "curie": "HGNC:9508", "type": "biolink:Gene", "role": "Presenilin 1 (gamma-secretase)" }, { "name": "MAPT", "curie": "HGNC:6893", "type": "biolink:Gene", "role": "Tau protein" }, { "name": "Alzheimer's Disease", "curie": "MONDO:0004975", "type": "biolink:Disease", "role": "Target disease" } ]
Gene(APP) --[interacts_with]--> Gene(PSEN1) --[associated_with]--> Disease(AD) <--[risk_factor]--> Gene(APOE)
[ "Anchor: hgnc_search_genes('APP') -> HGNC:620", "Expand: string_get_interactions('STRING:9606.ENSP00000284981') -> APP interactors", "Disease Links: opentargets_get_associations('ENSG00000142192') -> AD association scores", "Pathway Context: wikipathways_search_pathways('Alzheimer') -> WP:WP2059", "Persist: graphiti add_memory(group_id='cq3-alzheimers-gene-network')" ]
DALK (Li et al.)
Li, D., Yang, S., Tan, Z., et al. (2024). DALK: Dynamic Co-Augmentation of LLMs and KG to answer Alzheimer's Disease Questions with Scientific Literature. arXiv:2405.04819v1.
cq3-alzheimers-gene-network
[ "HGNC", "STRING", "Open Targets", "WikiPathways" ]
[ { "source": "HGNC:620", "target": "HGNC:9508", "predicate": "biolink:interacts_with" }, { "source": "HGNC:620", "target": "MONDO:0004975", "predicate": "biolink:gene_associated_with_condition" }, { "source": "HGNC:613", "target": "MONDO:0004975", "predicate": "biolink:gene_associated_with_condition" } ]
cq4
What drugs target amyloid-beta or tau proteins for Alzheimer's Disease treatment?
Therapeutic Target Discovery
Neurodegeneration (Alzheimer's)
multi_hop_traversal
advanced
4
[ { "name": "BACE1", "curie": "HGNC:933", "type": "biolink:Gene", "role": "Beta-secretase 1" }, { "name": "MAPT", "curie": "HGNC:6893", "type": "biolink:Gene", "role": "Tau protein" }, { "name": "GSK3B", "curie": "HGNC:4617", "type": "biolink:Gene", "role": "Tau kinase" }, { "name": "Lecanemab", "curie": "CHEMBL:4594344", "type": "biolink:SmallMolecule", "role": "Anti-amyloid antibody" } ]
Gene(BACE1) --[cleaves]--> Protein(APP) --[produces]--> Amyloid-beta <--[targets]--> Drug(Lecanemab)
[ "Anchor Targets: hgnc_search_genes('BACE1') -> HGNC:933", "Drug Discovery: chembl_search_compounds('BACE1 inhibitor')", "Activity Data: ChEMBL /activity -> binding affinities", "Clinical Trials: clinicaltrials_search_trials('Alzheimer BACE', phase='PHASE3')", "Persist: graphiti add_memory(group_id='cq4-alzheimers-therapeutics')" ]
DALK (Li et al.)
Li, D., Yang, S., Tan, Z., et al. (2024). DALK: Dynamic Co-Augmentation of LLMs and KG to answer Alzheimer's Disease Questions with Scientific Literature. arXiv:2405.04819v1.
cq4-alzheimers-therapeutics
[ "HGNC", "ChEMBL", "ClinicalTrials.gov" ]
[ { "source": "HGNC:933", "target": "HGNC:620", "predicate": "biolink:affects" }, { "source": "CHEMBL:4594344", "target": "HGNC:933", "predicate": "biolink:targets" } ]
cq5
In the MAPK signaling cascade, which proteins regulate downstream targets and with what direction (activation vs inhibition)?
Signaling Cascade Regulation
Oncology (MAPK pathway)
directed_traversal
intermediate
3
[ { "name": "RAF1", "curie": "STRING:9606.ENSP00000251849", "type": "biolink:Protein", "role": "MAPKKK" }, { "name": "MAP2K1", "curie": "STRING:9606.ENSP00000302486", "type": "biolink:Protein", "role": "MEK1" }, { "name": "MAPK1", "curie": "STRING:9606.ENSP00000215832", "type": "biolink:Protein", "role": "ERK2" } ]
Protein(RAF1) --[activates]--> Protein(MAP2K1/MEK1) --[activates]--> Protein(MAPK1/ERK2)
[ "Anchor: string_search_proteins('RAF1') -> STRING:9606.ENSP00000251849", "Directed Edges: string_get_interactions(required_score=700) -> Regulatory type", "Pathway Mapping: wikipathways_search_pathways('MAPK signaling') -> WP:WP382", "Disease Context: opentargets_get_associations() -> Cancer associations", "Persist: graphiti add_memory(group_id='cq5-mapk-regulatory-cascade')" ]
STRING 2025
Szklarczyk, D., Nastou, K., Koutrouli, M., et al. (2025). The STRING database in 2025: protein networks with directionality of regulation. Nucleic Acids Research, gkae1113.
cq5-mapk-regulatory-cascade
[ "STRING", "WikiPathways", "Open Targets" ]
[ { "source": "STRING:9606.ENSP00000251849", "target": "STRING:9606.ENSP00000302486", "predicate": "biolink:positively_regulates" }, { "source": "STRING:9606.ENSP00000302486", "target": "STRING:9606.ENSP00000215832", "predicate": "biolink:positively_regulates" } ]
cq6
What transcription factors regulate BRCA1 expression, and what genes does BRCA1 regulate?
Transcription Factor Network
Oncology (Breast Cancer)
bidirectional_expansion
advanced
3
[ { "name": "BRCA1", "curie": "HGNC:1100", "type": "biolink:Gene", "role": "Tumor suppressor" }, { "name": "E2F1", "curie": "HGNC:3113", "type": "biolink:Gene", "role": "Upstream TF" }, { "name": "SP1", "curie": "HGNC:11205", "type": "biolink:Gene", "role": "Upstream TF" }, { "name": "RAD51", "curie": "HGNC:9817", "type": "biolink:Gene", "role": "Downstream target" } ]
TF(E2F1) --[regulates]--> Gene(BRCA1) --[regulates]--> Gene(RAD51)
[ "Anchor: hgnc_search_genes('BRCA1') -> HGNC:1100", "Regulatory Network: string_get_interactions() -> Filter for regulatory edges", "Upstream TFs: Parse STRING regulatory evidence for edges pointing TO BRCA1", "Downstream Targets: Parse STRING for edges pointing FROM BRCA1", "Persist: graphiti add_memory(group_id='cq6-brca1-regulatory-network')" ]
STRING 2025
Szklarczyk, D., Nastou, K., Koutrouli, M., et al. (2025). The STRING database in 2025: protein networks with directionality of regulation. Nucleic Acids Research, gkae1113.
cq6-brca1-regulatory-network
[ "HGNC", "STRING" ]
[ { "source": "HGNC:3113", "target": "HGNC:1100", "predicate": "biolink:positively_regulates" }, { "source": "HGNC:11205", "target": "HGNC:1100", "predicate": "biolink:positively_regulates" }, { "source": "HGNC:1100", "target": "HGNC:9817", "predicate": "biolink:regulates" } ]
cq7
For NGLY1 deficiency, what are the associated genes, and what existing drugs target proteins in those pathways?
Multi-Hop Drug Repurposing
Rare Disease (NGLY1 Deficiency)
federated_multi_hop
advanced
5
[ { "name": "NGLY1", "curie": "HGNC:17646", "type": "biolink:Gene", "role": "Causal gene" }, { "name": "NGLY1 deficiency", "curie": "MONDO:0014109", "type": "biolink:Disease", "role": "Target disease" }, { "name": "N-glycanase pathway", "curie": "WP:WP5078", "type": "biolink:Pathway", "role": "Member pathway" } ]
Disease(NGLY1 deficiency) --[caused_by]--> Gene(NGLY1) --[participates_in]--> Pathway(N-glycanase) --[has_member]--> Gene(X) --[target_of]--> Drug(Y)
[ "Disease Anchor: Search for NGLY1 deficiency (MONDO:0014109)", "Gene Discovery: hgnc_search_genes('NGLY1') -> HGNC:17646", "Pathway Context: wikipathways_get_pathways_for_gene('NGLY1') -> Member pathways", "Pathway Expansion: wikipathways_get_pathway_components() -> All pathway members", "Drug Search: For each pathway protein -> chembl_search_compounds() with target filter", "Persist: graphiti add_memory(group_id='cq7-ngly1-drug-repurposing')" ]
BioThings Explorer
Callaghan, J., Xu, C.H., Xin, J., et al. (2023). BioThings Explorer: a query engine for a federated knowledge graph of biomedical APIs. Bioinformatics, btad570.
cq7-ngly1-drug-repurposing
[ "HGNC", "WikiPathways", "ChEMBL" ]
[ { "source": "MONDO:0014109", "target": "HGNC:17646", "predicate": "biolink:condition_associated_with_gene" }, { "source": "HGNC:17646", "target": "WP:WP5078", "predicate": "biolink:participates_in" } ]
cq8
How can we identify therapeutic strategies for ARID1A-deficient Ovarian Cancer using synthetic lethality?
Synthetic Lethality
Oncology (Ovarian Cancer)
multi_hop_traversal
advanced
4
[ { "name": "ARID1A", "curie": "HGNC:11110", "type": "biolink:Gene", "role": "Tumor suppressor (SWI/SNF)" }, { "name": "EZH2", "curie": "HGNC:3527", "type": "biolink:Gene", "role": "Synthetic lethal partner (PRC2)" }, { "name": "ATR", "curie": "HGNC:882", "type": "biolink:Gene", "role": "Synthetic lethal partner" }, { "name": "Tazemetostat", "curie": "CHEMBL:3414621", "type": "biolink:SmallMolecule", "role": "EZH2 inhibitor (FDA approved)" }, { "name": "NCT03348631", "curie": "NCT:03348631", "type": "biolink:ClinicalTrial", "role": "Phase 2 trial" } ]
Gene(ARID1A) --[synthetic_lethal_with]--> Gene(EZH2) --[target_of]--> Drug(Tazemetostat) --[tested_in]--> Trial(NCT03348631)
[ "Anchor: hgnc_search_genes('ARID1A') -> HGNC:11110", "Enrich: uniprot_get_protein('UniProtKB:O14497') -> SWI/SNF function", "Expand: string_get_interactions() -> SWI/SNF complex members", "Traverse: chembl_search_compounds('tazemetostat') -> CHEMBL:3414621", "Validate: ChEMBL /mechanism -> EZH2 inhibitor", "Persist: graphiti add_memory(group_id='cq8-arid1a-synthetic-lethality')" ]
Original
null
cq8-arid1a-synthetic-lethality
[ "HGNC", "UniProt", "STRING", "ChEMBL" ]
[ { "source": "HGNC:11110", "target": "HGNC:3527", "predicate": "biolink:genetically_interacts_with" }, { "source": "CHEMBL:3414621", "target": "HGNC:3527", "predicate": "biolink:targets" }, { "source": "CHEMBL:3414621", "target": "NCT:03348631", "predicate": "biolink:studied_in" } ]
cq9
What are the off-target risks of Dasatinib, specifically cardiotoxicity from hERG (KCNH2) and DDR2 activity?
Drug Safety / Off-Target Analysis
Oncology (CML)
comparative_analysis
advanced
3
[ { "name": "Dasatinib", "curie": "CHEMBL:1421", "type": "biolink:SmallMolecule", "role": "Index compound" }, { "name": "Imatinib", "curie": "CHEMBL:941", "type": "biolink:SmallMolecule", "role": "Cleaner alternative" }, { "name": "ABL1", "curie": "CHEMBL:1862", "type": "biolink:Gene", "role": "Primary target" }, { "name": "DDR2", "curie": "CHEMBL:5122", "type": "biolink:Gene", "role": "Off-target (pleural effusion)" }, { "name": "hERG/KCNH2", "curie": "HGNC:6251", "type": "biolink:Gene", "role": "Safety target (cardiotoxicity)" } ]
Drug(Dasatinib) --[targets]--> Gene(ABL1) AND Drug(Dasatinib) --[off_target]--> Gene(DDR2) --[causes]--> AE(pleural effusion)
[ "Anchor: chembl_search_compounds('dasatinib') -> CHEMBL:1421", "Mechanisms: ChEMBL /mechanism -> ABL1, PDGFR, KIT targets", "Activity: ChEMBL /activity -> IC50 values vs DDR2", "Compare: chembl_search_compounds('imatinib') -> cleaner profile", "Safety Genes: hgnc_search_genes('KCNH2') -> HGNC:6251", "Persist: graphiti add_memory(group_id='cq9-dasatinib-safety')" ]
Original
null
cq9-dasatinib-safety
[ "ChEMBL", "HGNC" ]
[ { "source": "CHEMBL:1421", "target": "CHEMBL:1862", "predicate": "biolink:targets" }, { "source": "CHEMBL:1421", "target": "CHEMBL:5122", "predicate": "biolink:targets" }, { "source": "CHEMBL:1421", "target": "HGNC:6251", "predicate": "biolink:targets" } ]
cq10
What novel therapeutic targets exist for Huntington's Disease that are not covered by current Phase 3 interventions?
Orphan Drug / Gap Analysis
Neurodegeneration (Huntington's)
set_difference
advanced
4
[ { "name": "HTT", "curie": "HGNC:4851", "type": "biolink:Gene", "role": "Causal gene" }, { "name": "SLC18A2/VMAT2", "curie": "CHEMBL:1893", "type": "biolink:Gene", "role": "Current target (covered)" }, { "name": "Tetrabenazine", "curie": "CHEMBL:117785", "type": "biolink:SmallMolecule", "role": "Approved drug" }, { "name": "SLC2A3/GLUT3", "curie": "ENSG00000059804", "type": "biolink:Gene", "role": "Novel target opportunity" } ]
Disease(HD) --[associated_with]--> Genes(all) MINUS Genes(Phase3_covered) = Genes(novel_targets)
[ "Anchor: hgnc_search_genes('HTT') -> HGNC:4851", "Trial Landscape: ClinicalTrials.gov -> Phase 3 trials", "Drug Mechanisms: ChEMBL /mechanism -> VMAT2 inhibitors", "Gap Analysis: opentargets_get_associations() -> ranked targets", "Find Novel: Filter for targets with no drug coverage", "Persist: graphiti add_memory(group_id='cq10-huntingtons-novel-targets')" ]
Original
null
cq10-huntingtons-novel-targets
[ "HGNC", "ClinicalTrials.gov", "ChEMBL", "Open Targets" ]
[ { "source": "HGNC:4851", "target": "MONDO:0007514", "predicate": "biolink:gene_associated_with_condition" }, { "source": "CHEMBL:117785", "target": "CHEMBL:1893", "predicate": "biolink:targets" } ]
cq11
How do we build and validate a knowledge graph for the p53-MDM2-Nutlin therapeutic axis?
Pathway Validation
Oncology (p53 pathway)
multi_hop_traversal
intermediate
3
[ { "name": "TP53", "curie": "HGNC:11998", "type": "biolink:Gene", "role": "Tumor suppressor" }, { "name": "MDM2", "curie": "HGNC:6973", "type": "biolink:Gene", "role": "Oncogene (E3 ligase)" }, { "name": "Nutlin-3", "curie": "CHEMBL:191334", "type": "biolink:SmallMolecule", "role": "MDM2 inhibitor" } ]
Gene(TP53) --[negatively_regulated_by]--> Gene(MDM2) --[target_of]--> Drug(Nutlin-3)
[ "Anchor: hgnc_search_genes('TP53') -> HGNC:11998", "Partner: hgnc_search_genes('MDM2') -> HGNC:6973", "Interactions: string_get_interactions() -> TP53-MDM2 (score 0.999)", "Drug: chembl_search_compounds('Nutlin-3') -> CHEMBL:191334", "Mechanism: ChEMBL /mechanism -> MDM2 inhibitor", "Persist: graphiti add_memory(group_id='cq11-p53-mdm2-nutlin')" ]
Original
null
cq11-p53-mdm2-nutlin
[ "HGNC", "STRING", "ChEMBL" ]
[ { "source": "HGNC:6973", "target": "HGNC:11998", "predicate": "biolink:negatively_regulates" }, { "source": "CHEMBL:191334", "target": "HGNC:6973", "predicate": "biolink:targets" } ]
cq12
What are the key health emergencies or emerging health priorities that multiple clinical trials are targeting right now?
Health Emergency Landscape
Cross-disease (Oncology, Diabetes, Neurodegeneration, Infectious Disease)
aggregation
advanced
2
[ { "name": "Cancer", "curie": null, "type": "biolink:Disease", "role": "18,636+ recruiting trials" }, { "name": "Diabetes", "curie": null, "type": "biolink:Disease", "role": "1,999+ trials" }, { "name": "Alzheimer's", "curie": "MONDO:0004975", "type": "biolink:Disease", "role": "579+ trials" }, { "name": "Long COVID", "curie": null, "type": "biolink:Disease", "role": "130+ trials" }, { "name": "CAR-T", "curie": null, "type": "biolink:Procedure", "role": "877+ trials" } ]
Disease(X) --[studied_in]--> Trials(recruiting, 2026) -> COUNT(*) GROUP BY disease ORDER BY count DESC
[ "Disease Discovery: clinicaltrials_search_trials() -> parallel searches by disease", "Innovation Discovery: Search CAR-T, GLP-1, immunotherapy, AI trials", "Pattern Analysis: Identify therapeutic convergence across diseases", "Persist: graphiti add_memory(group_id='cq12-health-emergencies-2026')" ]
Original
null
cq12-health-emergencies-2026
[ "ClinicalTrials.gov" ]
[]
cq13
Which clinical trials have the highest potential for commercialization or are attracting the most investment interest?
Commercialization Analysis
Cross-disease (Obesity, Oncology)
ranking
advanced
4
[ { "name": "Retatrutide", "curie": "NCT:07232719", "type": "biolink:ClinicalTrial", "role": "Eli Lilly - Obesity - VERY HIGH potential" }, { "name": "Sacituzumab Govitecan", "curie": "NCT:06486441", "type": "biolink:ClinicalTrial", "role": "Gilead - Endometrial Cancer - HIGH potential" }, { "name": "Ficerafusp Alfa", "curie": "NCT:06788990", "type": "biolink:ClinicalTrial", "role": "Bicara - Head & Neck Cancer - MODERATE-HIGH" } ]
Trial(X) --[tests]--> Drug(Y) --[targets]--> Gene(Z) --[associated_with]--> Disease(W) -> RANK BY market_potential
[ "Trial Discovery: clinicaltrials_search_trials(phase='PHASE3', status='RECRUITING')", "Drug Identification: chembl_search_compounds() -> CURIEs", "Mechanism Extraction: ChEMBL /mechanism -> Drug->Target edges", "Target Validation: opentargets_get_associations() -> disease associations", "Persist: graphiti add_memory(group_id='cq13-high-commercialization-trials')" ]
Original
null
cq13-high-commercialization-trials
[ "ClinicalTrials.gov", "ChEMBL", "Open Targets" ]
[]
cq14
How can we validate synthetic lethal gene pairs from Feng et al. (2022) and identify druggable opportunities for TP53-mutant cancers?
Synthetic Lethality Validation
Oncology (TP53-mutant cancers)
multi_hop_traversal
advanced
4
[ { "name": "TP53", "curie": "HGNC:11998", "type": "biolink:Gene", "role": "Tumor suppressor (50% of cancers)" }, { "name": "TYMS", "curie": "HGNC:12441", "type": "biolink:Gene", "role": "Synthetic lethal partner" }, { "name": "5-fluorouracil", "curie": "CHEMBL:185", "type": "biolink:SmallMolecule", "role": "TYMS inhibitor (approved)" }, { "name": "Pemetrexed", "curie": "CHEMBL:225072", "type": "biolink:SmallMolecule", "role": "TYMS inhibitor (approved)" } ]
Gene(TP53) --[synthetic_lethal_with]--> Gene(TYMS) --[target_of]--> Drug(Pemetrexed) --[in_trial]--> Trial(NCT04695925)
[ "Anchor: hgnc_search_genes('TP53') -> HGNC:11998, hgnc_search_genes('TYMS') -> HGNC:12441", "Validate: BioGRID ORCS -> 1,446 screens confirm TYMS essentiality", "Druggability: chembl_search_compounds('fluorouracil') -> CHEMBL:185", "Clinical: clinicaltrials_search_trials('TP53 pemetrexed') -> NCT:04695925", "Persist: graphiti add_memory(group_id='cq14-feng-synthetic-lethality')" ]
Feng et al. 2022
Feng et al., Sci. Adv. 8, eabm6638 (2022). PMC9098673.
cq14-feng-synthetic-lethality
[ "HGNC", "BioGRID", "ChEMBL", "ClinicalTrials.gov" ]
[ { "source": "HGNC:11998", "target": "HGNC:12441", "predicate": "biolink:genetically_interacts_with" }, { "source": "CHEMBL:225072", "target": "HGNC:12441", "predicate": "biolink:targets" }, { "source": "CHEMBL:225072", "target": "NCT:04695925", "predicate": "biolink:studied_in" } ]
cq15
Which CAR-T cell trials are currently navigating FDA or EMA milestones most rapidly? What regulatory hurdles are emerging in personalized medicine?
Regulatory Landscape Analysis
Oncology (Cell Therapy)
temporal_analysis
advanced
3
[ { "name": "CAR-T cell therapy", "curie": null, "type": "biolink:Procedure", "role": "Therapeutic modality" }, { "name": "ENACT-2", "curie": null, "type": "biolink:ClinicalTrial", "role": "Top velocity trial" }, { "name": "ABALL2", "curie": null, "type": "biolink:ClinicalTrial", "role": "Top velocity trial" }, { "name": "NXC-201", "curie": null, "type": "biolink:ClinicalTrial", "role": "Top velocity trial" } ]
Trial(X) --[uses]--> Therapy(CAR-T) --[phase]--> Milestone(FDA/EMA) -> RANK BY regulatory_velocity
[ "Trial Search: clinicaltrials_search_trials('CAR-T cell therapy', phase='PHASE3')", "Protocol Analysis: clinicaltrials_get_trial() -> sponsor, timeline, endpoints", "Drug Mechanisms: chembl_search_compounds() + /mechanism", "Regulatory Signals: Extract FDA/EMA designations from trial data", "Persist: graphiti add_memory(group_id='cq15-car-t-regulatory')" ]
Original
null
cq15-car-t-regulatory
[ "ClinicalTrials.gov", "ChEMBL" ]
[]

Open Biosciences Competency Questions (Sample)

Dataset Description

A curated collection of 15 competency questions (CQs) for evaluating and guiding knowledge graph construction in biosciences research. Each question includes structured entities with standardized CURIEs, gold-standard knowledge graph paths using BioLink predicates, executable multi-API workflow steps, and source provenance.

What Are Competency Questions?

Competency questions are natural language questions that a knowledge graph or ontology must be able to answer. Coined by Gruninger & Fox (1995), they serve as requirements specifications for knowledge representation systems -- defining scope, driving schema design, and providing testable acceptance criteria.

In biosciences, CQs bridge the gap between what a researcher wants to know ("By what mechanism does Palovarotene treat FOP?") and the structured graph traversals needed to answer it (Drug --[agonist_of]--> Gene --[regulates]--> Gene --[associated_with]--> Disease).

Why This Dataset?

Existing biomedical QA benchmarks (PubMedQA, BioASQ, MedQA, PrimeKGQA) provide large-scale evaluation but lack:

Feature This Dataset PrimeKGQA BioASQ MedReason
Standardized CURIEs (HGNC, CHEMBL, MONDO) Yes No Partial No
BioLink-typed entities & predicates Yes No No No
Gold standard graph paths Yes SPARQL Triples Text
Executable API workflow steps Yes No No No
Multi-database federation Yes Single KG PubMed Single KG
Fuzzy-to-Fact discovery protocol Yes No No No

This dataset is small by design -- it prioritizes depth of annotation per question over breadth, making each CQ a complete, reproducible research workflow specification.

Supported Tasks

  • Knowledge Graph Evaluation: Test whether a KG can answer domain research questions
  • Multi-Hop Biomedical Reasoning: Benchmark for graph traversal across genes, drugs, diseases, pathways
  • API Workflow Validation: Executable steps for testing biosciences MCP server integrations
  • Entity Resolution Benchmarking: CURIE-grounded evaluation of fuzzy-to-fact discovery
  • Ontology Engineering: Template for authoring new competency questions

Dataset Structure

Schema

Field Type Description
cq_id string Unique identifier (e.g., "cq1")
question string Natural language research question
category string Domain category (e.g., "Drug Mechanism of Action", "Synthetic Lethality")
disease_area string Therapeutic area (e.g., "Rare Disease (FOP)", "Oncology")
reasoning_type string Graph reasoning pattern required
complexity string intermediate or advanced
num_hops int Number of hops in the gold standard path
key_entities list[dict] Entities with name, curie, type (BioLink), role
gold_standard_path string Expected node-edge-node traversal chain
workflow_steps list[string] Ordered API calls to answer the question
source string Origin (DrugMechDB, DALK, STRING 2025, BioThings, Feng et al., Original)
source_reference string? Academic citation if applicable
group_id string Graphiti knowledge graph persistence target
apis_used list[string] APIs required (HGNC, ChEMBL, STRING, etc.)
biolink_edges list[dict] Typed edges with source, target, predicate

Reasoning Types

Type Description Example CQs
multi_hop_traversal Follow a chain of typed edges cq1, cq2, cq4, cq8, cq11, cq14
network_expansion Expand outward from anchor node(s) cq3
directed_traversal Follow regulatory direction (activation/inhibition) cq5
bidirectional_expansion Expand both upstream and downstream cq6
federated_multi_hop Multi-hop across federated APIs cq7
comparative_analysis Compare entities side-by-side cq9
set_difference Find elements in set A not in set B cq10
aggregation Count, group, rank across entities cq12
ranking Order by computed metric cq13
temporal_analysis Track progression over time cq15

Categories

Category Count CQs
Drug Mechanism / Repurposing 3 cq1, cq2, cq7
Gene-Protein Networks 2 cq3, cq6
Therapeutic Target Discovery 2 cq4, cq10
Synthetic Lethality 2 cq8, cq14
Signaling / Pathway Validation 2 cq5, cq11
Drug Safety 1 cq9
Clinical Trial Landscape 2 cq12, cq13
Regulatory Analysis 1 cq15

Example Instance (cq1)

{
  "cq_id": "cq1",
  "question": "By what mechanism does Palovarotene treat Fibrodysplasia Ossificans Progressiva (FOP)?",
  "category": "Drug Mechanism of Action",
  "disease_area": "Rare Disease (FOP)",
  "reasoning_type": "multi_hop_traversal",
  "complexity": "intermediate",
  "num_hops": 3,
  "key_entities": [
    {"name": "Palovarotene", "curie": "CHEMBL:2105648", "type": "biolink:SmallMolecule", "role": "RAR-gamma agonist"},
    {"name": "RARG", "curie": "HGNC:9866", "type": "biolink:Gene", "role": "Retinoic acid receptor gamma"},
    {"name": "ACVR1", "curie": "HGNC:171", "type": "biolink:Gene", "role": "BMP receptor (causal gene)"},
    {"name": "FOP", "curie": "MONDO:0007606", "type": "biolink:Disease", "role": "Target disease"}
  ],
  "gold_standard_path": "Drug(Palovarotene) --[agonist]--> Protein(RARG) --[regulates]--> Protein(ACVR1) --[causes]--> Disease(FOP)",
  "workflow_steps": [
    "Anchor: chembl_search_compounds('palovarotene') -> CHEMBL:2105648",
    "Enrich: chembl_get_compound('CHEMBL:2105648') -> Max Phase 4, indications",
    "Mechanism: ChEMBL /mechanism -> RARG agonist",
    "Target Gene: hgnc_get_gene('HGNC:171') -> ACVR1 details",
    "Disease Link: opentargets_get_associations('ENSG00000115170') -> FOP association",
    "Persist: graphiti add_memory(group_id='cq1-fop-mechanism')"
  ],
  "source": "DrugMechDB",
  "apis_used": ["ChEMBL", "HGNC", "Open Targets"],
  "biolink_edges": [
    {"source": "CHEMBL:2105648", "target": "HGNC:9866", "predicate": "biolink:agonist_of"},
    {"source": "HGNC:9866", "target": "HGNC:171", "predicate": "biolink:regulates"},
    {"source": "HGNC:171", "target": "MONDO:0007606", "predicate": "biolink:gene_associated_with_condition"}
  ]
}

Dataset Creation

Curation Rationale

These 15 CQs were designed to cover the core reasoning patterns needed for AI-powered biosciences research:

  • Mechanistic questions (cq1, cq5, cq11): How does drug X work? What regulates gene Y?
  • Discovery questions (cq2, cq7, cq10): What drugs could be repurposed? What targets are uncovered?
  • Safety questions (cq9): What are the off-target risks?
  • Validation questions (cq8, cq14): Can we confirm synthetic lethal relationships?
  • Landscape questions (cq12, cq13, cq15): What does the trial/regulatory landscape look like?

The CQs span rare diseases (FOP, NGLY1 deficiency, Huntington's), common diseases (Alzheimer's, cancer), and cross-cutting concerns (drug safety, clinical trial prioritization).

Source Data

Source CQs Description
DrugMechDB cq1, cq2 Drug mechanism database patterns
Li et al. (2024) DALK cq3, cq4 Alzheimer's KG from 9,764 PubMed papers
Szklarczyk et al. (2025) STRING cq5, cq6 Directed regulatory networks
Callaghan et al. (2023) BioThings cq7 Federated KG from 34 biomedical APIs
Feng et al. (2022) cq14 209 synthetic lethal gene pairs
Original research cq8-13, cq15 Novel questions for this project

Annotations

Each CQ was:

  1. Authored by domain researchers following the Fuzzy-to-Fact protocol
  2. Validated by executing workflow steps against live biosciences MCP API servers (12 FastMCP servers covering HGNC, UniProt, ChEMBL, Open Targets, STRING, BioGRID, Ensembl, Entrez, PubChem, IUPHAR, WikiPathways, ClinicalTrials.gov)
  3. Persisted to a Graphiti knowledge graph with dedicated group_id namespaces

CQ Type Classification (Keet & Khan 2024)

Following the ROCQS taxonomy of competency question types:

CQ Type Abbreviation Present In
Scoping SCQ cq3 ("What genes are implicated..."), cq12, cq15
Validating VCQ cq11 ("How do we validate..."), cq14
Relationship RCQ cq1, cq5, cq6, cq8, cq9
Foundational FCQ Implicit in BioLink typing
Metaproperty MpCQ Not directly represented

Considerations

Known Limitations

  • Small size: 15 CQs -- designed as a sample/template, not a large-scale benchmark
  • CURIE staleness: Database identifiers may change as HGNC, ChEMBL, etc. update
  • API dependency: Workflow steps require access to external biosciences APIs
  • Domain skew: Oncology and rare disease overrepresented; infectious disease underrepresented
  • English only: All questions and annotations in English

Relation to Other Datasets

  • Complements PrimeKGQA (84K pairs, single-KG SPARQL) with multi-API federation
  • Extends BioASQ concept by adding executable graph paths
  • Parallels MedReason (32K pairs) but with CURIE-grounded rather than text-only reasoning
  • Builds on CQ-to-SPARQL-OWL (234 CQs) methodology for biosciences domain

Future Extensions

  • Paul Zamora's 12 oncology CQs (Doxorubicin toxicity, tumor microenvironment, NSCLC synthetic lethality)
  • Additional CQs from community contributions
  • Validation result datasets with API response snapshots
  • HuggingFace Datasets versioning for reproducible evaluation

References

  1. Gruninger, M. & Fox, M.S. (1995). "The Role of Competency Questions in Enterprise Engineering." IFIP AICT.
  2. Ren, Y. et al. (2014). "Towards Competency Question-Driven Ontology Authoring." ESWC 2014.
  3. Wisniewski, D. et al. (2019). "Analysis of Ontology Competency Questions and their Formalizations in SPARQL-OWL." J. Web Semantics.
  4. Bezerra, C. et al. (2023). "Use of Competency Questions in Ontology Engineering: A Survey." ER 2023.
  5. Keet, C.M. & Khan, Z.C. (2024). "Discerning and Characterising Types of Competency Questions for Ontologies." EKAW 2024.
  6. Li, D. et al. (2024). "DALK: Dynamic Co-Augmentation of LLMs and KG." EMNLP 2024 Findings.
  7. Szklarczyk, D. et al. (2025). "STRING 2025: protein networks with directionality." Nucleic Acids Res.

Citation

@dataset{open_biosciences_cq_2026,
  title={Open Biosciences Competency Questions (Sample)},
  author={Open Biosciences Project},
  year={2026},
  url={https://huggingface.co/datasets/open-biosciences/biosciences-competency-questions-sample},
  license={MIT}
}

Project Context

Part of the Open Biosciences platform -- a multi-repo workspace for AI-powered biosciences research. Maintained by the Research Workflows Engineer (Agent #6).

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