cq_id string | question string | category string | disease_area string | reasoning_type string | complexity string | num_hops int64 | key_entities list | gold_standard_path string | workflow_steps list | source string | source_reference string | group_id string | apis_used list | biolink_edges list |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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",
"... | 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('ENSG000001... | 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_condi... |
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": "biol... | 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 a... | 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": "biolin... | 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:... | 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:gen... |
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... | 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-alzh... | 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",... | 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",
... | 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": "Ups... | 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(gro... | 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":... | 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 e... | 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": "b... | 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",
... | 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:studi... |
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",
"ty... | 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",
"Pers... | 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": "b... | 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 a... | 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:SmallM... | 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... | 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:Dise... | 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 poten... | 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 a... | 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",
... | 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",
... | 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:studi... |
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:C... | 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: graphi... | Original | null | cq15-car-t-regulatory | [
"ClinicalTrials.gov",
"ChEMBL"
] | [] |
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