Multi-omics Data Integration

Building on the Single omics integration, we further enhance biological insight by connecting other omics data types (proteomics, metabolomics) and ontology information directly into the knowledge graph. Linking standardized biomedical ontologies—such as the Gene Ontology (GO), Disease Ontology (MONDO) and phenotype (EFO, HPO) which enriches the multi-omics graph with layers of curated knowledge. Each gene, protein, metabolite, or biological entity in the graph can be annotated with relevant ontology terms, enabling not just data integration, but deep semantic enrichment.

This ontology-driven approach allows researchers to query molecular data in concept-driven ways: for example, finding all genes participating in a specific biological process (GO term), all proteins annotated as drug targets, or all molecular entities linked to a disease category across experiments. By linking omics data to ontological nodes and relationships, the knowledge graph supports cross-omics reasoning (e.g., transcript changes that impact disease-relevant pathways), leverages hierarchical vocabulary structures for inference, and enables federated analysis across datasets and domains. The result is a truly interconnected data and knowledge landscape—accelerating hypothesis generation, translational discovery, and precision medicine.

Scenario

Building on the Single omics foundation, we now extend the integration to support multiple omics layers such as proteomics and metabolomics. By mapping relationships between genes, their protein products, and metabolic pathways, the knowledge graph captures the full spectrum from transcriptomics through proteomics to metabolomic contexts. This unified representation enables researchers to trace molecular changes across different omics types and gain holistic insights into biological systems and disease mechanisms. We will also add ontology information to the nodes and relationships to enrich the graph with layers of curated knowledge.

Data Model

This data model extends the Single omics Data Integration page by adding more omics data like proteomics and metabolomics as well as data from ontologies like GO and EFO:

New Protein Nodes Added
New Ontology Nodes Added
New Ontology Relationships Added
New Proteomics Experiments Added
New Metabolomics Experiments Added
New Multi-omics Comparison (COMP009)

The (Experiment)-[:HAS_VALUE]→(Protein) relationships now include:

logFC: Protein abundance change1
pValue: Statistical significance
regulated: up/down direction
intensity: MS intensity values
peptides: Number of peptides identified
coverage: Protein sequence coverage percentage

Multi-omics Comparison (COMP009)

A new comparison integrating transcriptomics and proteomics for NAFLD, including:

RNA-seq (EXP001)
Proteomics TMT-MS (EXP004)
Proteomics DIA-PASEF (EXP007)
Correlation values showing mRNA-protein concordance

Industry Use Cases multi omics with ontologies

Demo Data

The following Cypher statements will create the example graph in the Neo4j database:

// MERGE Projects
MERGE (p1:Project {sid: "PROJ001", name: "Liver Disease Study"})
MERGE (p2:Project {sid: "PROJ002", name: "Diabetes Research"})
MERGE (p3:Project {sid: "PROJ003", name: "Cross-Disease Metabolic Study"})

// MERGE Tissues
MERGE (t1:Tissue {sid: "UBERON:0002107", name: "Liver"})
MERGE (t2:Tissue {sid: "UBERON:0001264", name: "Pancreas"})
MERGE (t3:Tissue {sid: "UBERON:0000945", name: "Adipose tissue"})

// MERGE Diseases
MERGE (d1:Disease {sid: "MONDO:0005359", name: "Non-alcoholic fatty liver disease"})
MERGE (d2:Disease {sid: "MONDO:0005015", name: "Type 2 Diabetes"})
MERGE (d3:Disease {sid: "MONDO:0011382", name: "Metabolic Syndrome"})

// MERGE Phenotypes (EFO)
MERGE (ph1:EFO {sid: "EFO:0004220", name: "Insulin resistance"})
MERGE (ph2:EFO {sid: "EFO:0001421", name: "Elevated triglycerides"})
MERGE (ph3:EFO {sid: "EFO:0004465", name: "Hepatic steatosis"})
MERGE (ph4:EFO {sid: "EFO:0000685", name: "Obesity"})

// MERGE Samples
MERGE (s1:Sample {sid: "SAMPLE001", name: "Patient_001_Liver", condition: "NAFLD"})
MERGE (s2:Sample {sid: "SAMPLE002", name: "Control_001_Liver", condition: "Healthy"})
MERGE (s3:Sample {sid: "SAMPLE003", name: "Patient_002_Pancreas", condition: "T2D"})
MERGE (s4:Sample {sid: "SAMPLE004", name: "Control_002_Pancreas", condition: "Healthy"})
MERGE (s5:Sample {sid: "SAMPLE005", name: "Patient_003_Liver", condition: "NAFLD"})
MERGE (s6:Sample {sid: "SAMPLE006", name: "Patient_004_Adipose", condition: "MetSyn"})
MERGE (s7:Sample {sid: "SAMPLE007", name: "Control_003_Adipose", condition: "Healthy"})

// MERGE Experiments - RNA-seq
MERGE (e1:Experiment {sid: "EXP001", type: "RNA-seq", platform: "Illumina NovaSeq"})
MERGE (e2:Experiment {sid: "EXP002", type: "RNA-seq", platform: "Illumina NovaSeq"})
MERGE (e3:Experiment {sid: "EXP003", type: "RNA-seq", platform: "Illumina NovaSeq"})

// MERGE Experiments - Proteomics
MERGE (e4:Experiment {sid: "EXP004", type: "Proteomics", platform: "Orbitrap Fusion", method: "TMT-MS"})
MERGE (e5:Experiment {sid: "EXP005", type: "Proteomics", platform: "Orbitrap Fusion", method: "TMT-MS"})
MERGE (e6:Experiment {sid: "EXP006", type: "Proteomics", platform: "Q Exactive HF", method: "Label-free quantification"})
MERGE (e7:Experiment {sid: "EXP007", type: "Proteomics", platform: "timsTOF Pro", method: "DIA-PASEF"})

// ============================================
// EXTENDED COMPARISON NODES
// ============================================

// Basic disease vs control comparisons
MERGE (comp1:Comparison {
  sid: "COMP001",
  name: "NAFLD vs Control (Liver)",
  type: "disease_vs_control",
  tissue: "Liver",
  n_case: 2,
  n_control: 1,
  analysis_date: "2024-01-15"
})

MERGE (comp2:Comparison {
  sid: "COMP002",
  name: "T2D vs Control (Pancreas)",
  type: "disease_vs_control",
  tissue: "Pancreas",
  n_case: 1,
  n_control: 1,
  analysis_date: "2024-01-20"
})

MERGE (comp3:Comparison {
  sid: "COMP003",
  name: "Metabolic Syndrome vs Control (Adipose)",
  type: "disease_vs_control",
  tissue: "Adipose",
  n_case: 1,
  n_control: 1,
  analysis_date: "2024-02-01"
})

// Cross-tissue comparisons (same disease, different tissues)
MERGE (comp4:Comparison {
  sid: "COMP004",
  name: "NAFLD Liver vs T2D Pancreas",
  type: "cross_tissue_disease",
  tissue: "Liver vs Pancreas",
  description: "Compare molecular signatures between NAFLD and T2D",
  analysis_date: "2024-02-10"
})


// Phenotype-based comparison
MERGE (comp6:Comparison {
  sid: "COMP006",
  name: "Insulin Resistant vs Non-Resistant",
  type: "phenotype_stratified",
  stratification: "Insulin resistance status",
  description: "Compare samples with vs without insulin resistance",
  analysis_date: "2024-02-20"
})



// Multi-disease meta-analysis
MERGE (comp8:Comparison {
  sid: "COMP008",
  name: "Pan-Metabolic Disease Signature",
  type: "meta_analysis",
  diseases: "NAFLD, T2D, MetSyn",
  description: "Common molecular signatures across metabolic diseases",
  analysis_date: "2024-03-05"
})

// ============================================
// MERGE GENES with expression data
// ============================================

MERGE (g1:Gene {sid: "ENSG00000105851", symbol: "PIK3CG", name: "Phosphatidylinositol-3-kinase catalytic gamma", source: "Ensembl"})
MERGE (g2:Gene {sid: "ENSG00000169245", symbol: "CXCL10", name: "C-X-C motif chemokine ligand 10", source: "Ensembl"})
MERGE (g3:Gene {sid: "ENSG00000198793", symbol: "MTOR", name: "Mechanistic target of rapamycin kinase", source: "Ensembl"})
MERGE (g4:Gene {sid: "ENSG00000134108", symbol: "AKT1", name: "AKT serine/threonine kinase 1", source: "Ensembl"})
MERGE (g5:Gene {sid: "ENSG00000171408", symbol: "PPARG", name: "Peroxisome proliferator activated receptor gamma", source: "Ensembl"})
MERGE (g6:Gene {sid: "ENSG00000108932", symbol: "CD36", name: "CD36 molecule", source: "Ensembl"})
MERGE (g7:Gene {sid: "ENSG00000163631", symbol: "ALB", name: "Albumin", source: "Ensembl"})
MERGE (g8:Gene {sid: "ENSG00000169429", symbol: "CXCL8", name: "C-X-C motif chemokine ligand 8", source: "Ensembl"})

// MERGE IDs (alternative identifiers)
MERGE (id1:ID {sid: "5294", source: "NCBI"})
MERGE (id2:ID {sid: "3627", source: "NCBI"})
MERGE (id3:ID {sid: "2475", source: "NCBI"})
MERGE (id4:ID {sid: "207", source: "NCBI"})
MERGE (id5:ID {sid: "5468", source: "NCBI"})

// MERGE Proteins
MERGE (pr1:Protein {sid: "P48736", source: "UniProt", name: "PIK3CG", gene_name: "PIK3CG"})
MERGE (pr2:Protein {sid: "P02778", source: "UniProt", name: "CXCL10", gene_name: "CXCL10"})
MERGE (pr3:Protein {sid: "P42345", source: "UniProt", name: "MTOR", gene_name: "MTOR"})
MERGE (pr4:Protein {sid: "P31749", source: "UniProt", name: "AKT1", gene_name: "AKT1"})
MERGE (pr5:Protein {sid: "P37231", source: "UniProt", name: "PPARG", gene_name: "PPARG"})
MERGE (pr6:Protein {sid: "P16671", source: "UniProt", name: "CD36", gene_name: "CD36"})
MERGE (pr7:Protein {sid: "P02768", source: "UniProt", name: "ALB", gene_name: "ALB"})
MERGE (pr8:Protein {sid: "P05067", source: "UniProt", name: "APP", gene_name: "APP"})
MERGE (pr9:Protein {sid: "P01308", source: "UniProt", name: "INS", gene_name: "INS"})
MERGE (pr10:Protein {sid: "P10636", source: "UniProt", name: "MAPT", gene_name: "MAPT"})
MERGE (pr11:Protein {sid: "P35354", source: "UniProt", name: "PTGS2", gene_name: "PTGS2"})
MERGE (pr12:Protein {sid: "P01375", source: "UniProt", name: "TNF", gene_name: "TNF"})

// MERGE GO terms
MERGE (go1:GO {sid: "GO:0005158", name: "insulin receptor binding"})
MERGE (go2:GO {sid: "GO:0006954", name: "inflammatory response"})
MERGE (go3:GO {sid: "GO:0043066", name: "negative regulation of apoptosis"})
MERGE (go4:GO {sid: "GO:0008286", name: "insulin receptor signaling pathway"})
MERGE (go5:GO {sid: "GO:0006629", name: "lipid metabolic process"})
MERGE (go6:GO {sid: "GO:0006955", name: "immune response"})
MERGE (go7:GO {sid: "GO:0071356", name: "cellular response to tumor necrosis factor"})
MERGE (go8:GO {sid: "GO:0042593", name: "glucose homeostasis"})
MERGE (go9:GO {sid: "GO:0006006", name: "glucose metabolic process"})
MERGE (go10:GO {sid: "GO:0030154", name: "cell differentiation"})
MERGE (go11:GO {sid: "GO:0051091", name: "positive regulation of transcription factor activity"})

// MERGE Pathway nodes (higher-level biological pathways)
MERGE (pw1:Pathway {sid: "KEGG:04910", name: "Insulin signaling pathway", source: "KEGG"})
MERGE (pw2:Pathway {sid: "KEGG:04064", name: "NF-kappa B signaling pathway", source: "KEGG"})
MERGE (pw3:Pathway {sid: "KEGG:04151", name: "PI3K-Akt signaling pathway", source: "KEGG"})
MERGE (pw4:Pathway {sid: "KEGG:04150", name: "mTOR signaling pathway", source: "KEGG"})
MERGE (pw5:Pathway {sid: "KEGG:04920", name: "Adipocytokine signaling pathway", source: "KEGG"})
MERGE (pw6:Pathway {sid: "KEGG:03320", name: "PPAR signaling pathway", source: "KEGG"})
MERGE (pw7:Pathway {sid: "REACTOME:R-HSA-74751", name: "Insulin receptor signaling cascade", source: "Reactome"})
MERGE (pw8:Pathway {sid: "REACTOME:R-HSA-449147", name: "Signaling by Interleukins", source: "Reactome"})
MERGE (pw10:Pathway {sid: "WIKIPATHWAYS:WP1471", name: "Inflammatory Response Pathway", source: "WikiPathways"});

// ============================================
// RELATIONSHIPS: PROJECT -> SAMPLE
// ============================================

MATCH (p:Project {sid: "PROJ001"}), (s:Sample {sid: "SAMPLE001"})
MERGE (p)-[:HAS_SAMPLE]->(s);
MATCH (p:Project {sid: "PROJ001"}), (s:Sample {sid: "SAMPLE002"})
MERGE (p)-[:HAS_SAMPLE]->(s);
MATCH (p:Project {sid: "PROJ001"}), (s:Sample {sid: "SAMPLE005"})
MERGE (p)-[:HAS_SAMPLE]->(s);

MATCH (p:Project {sid: "PROJ002"}), (s:Sample {sid: "SAMPLE003"})
MERGE (p)-[:HAS_SAMPLE]->(s);
MATCH (p:Project {sid: "PROJ002"}), (s:Sample {sid: "SAMPLE004"})
MERGE (p)-[:HAS_SAMPLE]->(s);

MATCH (p:Project {sid: "PROJ003"}), (s:Sample {sid: "SAMPLE006"})
MERGE (p)-[:HAS_SAMPLE]->(s);
MATCH (p:Project {sid: "PROJ003"}), (s:Sample {sid: "SAMPLE007"})
MERGE (p)-[:HAS_SAMPLE]->(s);

// ============================================
// RELATIONSHIPS: SAMPLE -> TISSUE
// ============================================

MATCH (s:Sample {sid: "SAMPLE001"}), (t:Tissue {sid: "UBERON:0002107"})
MERGE (s)-[:TAKEN_FROM]->(t);
MATCH (s:Sample {sid: "SAMPLE002"}), (t:Tissue {sid: "UBERON:0002107"})
MERGE (s)-[:TAKEN_FROM]->(t);
MATCH (s:Sample {sid: "SAMPLE005"}), (t:Tissue {sid: "UBERON:0002107"})
MERGE (s)-[:TAKEN_FROM]->(t);

MATCH (s:Sample {sid: "SAMPLE003"}), (t:Tissue {sid: "UBERON:0001264"})
MERGE (s)-[:TAKEN_FROM]->(t);
MATCH (s:Sample {sid: "SAMPLE004"}), (t:Tissue {sid: "UBERON:0001264"})
MERGE (s)-[:TAKEN_FROM]->(t);

MATCH (s:Sample {sid: "SAMPLE006"}), (t:Tissue {sid: "UBERON:0000945"})
MERGE (s)-[:TAKEN_FROM]->(t);
MATCH (s:Sample {sid: "SAMPLE007"}), (t:Tissue {sid: "UBERON:0000945"})
MERGE (s)-[:TAKEN_FROM]->(t);

// ============================================
// RELATIONSHIPS: SAMPLE -> PHENOTYPE
// ============================================

MATCH (s:Sample {sid: "SAMPLE001"}), (ph:EFO {sid: "EFO:0001421"})
MERGE (s)-[:HAS_PHENOTYPE]->(ph);
MATCH (s:Sample {sid: "SAMPLE001"}), (ph:EFO {sid: "EFO:0004465"})
MERGE (s)-[:HAS_PHENOTYPE]->(ph);

MATCH (s:Sample {sid: "SAMPLE003"}), (ph:EFO {sid: "EFO:0004220"})
MERGE (s)-[:HAS_PHENOTYPE]->(ph);

MATCH (s:Sample {sid: "SAMPLE005"}), (ph:EFO {sid: "EFO:0004465"})
MERGE (s)-[:HAS_PHENOTYPE]->(ph);

MATCH (s:Sample {sid: "SAMPLE006"}), (ph:EFO {sid: "EFO:0000685"})
MERGE (s)-[:HAS_PHENOTYPE]->(ph);
MATCH (s:Sample {sid: "SAMPLE006"}), (ph:EFO {sid: "EFO:0004220"})
MERGE (s)-[:HAS_PHENOTYPE]->(ph);

// ============================================
// RELATIONSHIPS: SAMPLE -> EXPERIMENT
// ============================================

MATCH (s:Sample {sid: "SAMPLE001"}), (e:Experiment {sid: "EXP001"})
MERGE (s)-[:HAS_EXPERIMENT]->(e);
MATCH (s:Sample {sid: "SAMPLE002"}), (e:Experiment {sid: "EXP001"})
MERGE (s)-[:HAS_EXPERIMENT]->(e);
MATCH (s:Sample {sid: "SAMPLE005"}), (e:Experiment {sid: "EXP001"})
MERGE (s)-[:HAS_EXPERIMENT]->(e);

MATCH (s:Sample {sid: "SAMPLE003"}), (e:Experiment {sid: "EXP002"})
MERGE (s)-[:HAS_EXPERIMENT]->(e);
MATCH (s:Sample {sid: "SAMPLE004"}), (e:Experiment {sid: "EXP002"})
MERGE (s)-[:HAS_EXPERIMENT]->(e);

MATCH (s:Sample {sid: "SAMPLE006"}), (e:Experiment {sid: "EXP003"})
MERGE (s)-[:HAS_EXPERIMENT]->(e);
MATCH (s:Sample {sid: "SAMPLE007"}), (e:Experiment {sid: "EXP003"})
MERGE (s)-[:HAS_EXPERIMENT]->(e);

// Connect samples to proteomics experiments
MATCH (s:Sample {sid: "SAMPLE001"}), (e:Experiment {sid: "EXP004"})
MERGE (s)-[:HAS_EXPERIMENT]->(e);
MATCH (s:Sample {sid: "SAMPLE002"}), (e:Experiment {sid: "EXP004"})
MERGE (s)-[:HAS_EXPERIMENT]->(e);
MATCH (s:Sample {sid: "SAMPLE005"}), (e:Experiment {sid: "EXP004"})
MERGE (s)-[:HAS_EXPERIMENT]->(e);

MATCH (s:Sample {sid: "SAMPLE003"}), (e:Experiment {sid: "EXP005"})
MERGE (s)-[:HAS_EXPERIMENT]->(e);
MATCH (s:Sample {sid: "SAMPLE004"}), (e:Experiment {sid: "EXP005"})
MERGE (s)-[:HAS_EXPERIMENT]->(e);

MATCH (s:Sample {sid: "SAMPLE006"}), (e:Experiment {sid: "EXP006"})
MERGE (s)-[:HAS_EXPERIMENT]->(e);
MATCH (s:Sample {sid: "SAMPLE007"}), (e:Experiment {sid: "EXP006"})
MERGE (s)-[:HAS_EXPERIMENT]->(e);

// Additional cross-platform experiment
MATCH (s:Sample {sid: "SAMPLE001"}), (e:Experiment {sid: "EXP007"})
MERGE (s)-[:HAS_EXPERIMENT]->(e);
MATCH (s:Sample {sid: "SAMPLE002"}), (e:Experiment {sid: "EXP007"})
MERGE (s)-[:HAS_EXPERIMENT]->(e);

// ============================================
// RELATIONSHIPS: COMPARISON -> EXPERIMENT
// ============================================

// Basic comparisons to experiments
MATCH (c:Comparison {sid: "COMP001"}), (e:Experiment {sid: "EXP001"})
MERGE (c)-[:COMPARES]->(e);

MATCH (c:Comparison {sid: "COMP002"}), (e:Experiment {sid: "EXP002"})
MERGE (c)-[:COMPARES]->(e);

MATCH (c:Comparison {sid: "COMP003"}), (e:Experiment {sid: "EXP003"})
MERGE (c)-[:COMPARES]->(e);

// Cross-tissue comparison
MATCH (c:Comparison {sid: "COMP004"}), (e:Experiment {sid: "EXP001"})
MERGE (c)-[:COMPARES]->(e);
MATCH (c:Comparison {sid: "COMP004"}), (e:Experiment {sid: "EXP002"})
MERGE (c)-[:COMPARES]->(e);

// Proteomics comparisons
MATCH (c:Comparison {sid: "COMP001"}), (e:Experiment {sid: "EXP004"})
MERGE (c)-[:COMPARES]->(e);

MATCH (c:Comparison {sid: "COMP002"}), (e:Experiment {sid: "EXP005"})
MERGE (c)-[:COMPARES]->(e);

MATCH (c:Comparison {sid: "COMP003"}), (e:Experiment {sid: "EXP006"})
MERGE (c)-[:COMPARES]->(e);

// Meta-analysis comparison (all experiments including proteomics)
MATCH (c:Comparison {sid: "COMP008"}), (e:Experiment {sid: "EXP001"})
MERGE (c)-[:COMPARES]->(e);
MATCH (c:Comparison {sid: "COMP008"}), (e:Experiment {sid: "EXP002"})
MERGE (c)-[:COMPARES]->(e);
MATCH (c:Comparison {sid: "COMP008"}), (e:Experiment {sid: "EXP003"})
MERGE (c)-[:COMPARES]->(e);
MATCH (c:Comparison {sid: "COMP008"}), (e:Experiment {sid: "EXP004"})
MERGE (c)-[:COMPARES]->(e);
MATCH (c:Comparison {sid: "COMP008"}), (e:Experiment {sid: "EXP005"})
MERGE (c)-[:COMPARES]->(e);
MATCH (c:Comparison {sid: "COMP008"}), (e:Experiment {sid: "EXP006"})
MERGE (c)-[:COMPARES]->(e);

// Create multi-omics integration comparison
MERGE (comp9:Comparison {
  sid: "COMP009",
  name: "Multi-omics NAFLD Integration",
  type: "multi_omics_integration",
  tissue: "Liver",
  description: "Integrated transcriptomics and proteomics analysis of NAFLD",
  analysis_date: "2024-03-10"
});

MATCH (c:Comparison {sid: "COMP009"}), (e:Experiment {sid: "EXP001"})
MERGE (c)-[:COMPARES]->(e);
MATCH (c:Comparison {sid: "COMP009"}), (e:Experiment {sid: "EXP004"})
MERGE (c)-[:COMPARES]->(e);
MATCH (c:Comparison {sid: "COMP009"}), (e:Experiment {sid: "EXP007"})
MERGE (c)-[:COMPARES]->(e);

MATCH (c:Comparison {sid: "COMP009"}), (d:Disease {sid: "MONDO:0005359"})
MERGE (c)-[:STUDIES_DISEASE]->(d);

// ============================================
// RELATIONSHIPS: COMPARISON -> SAMPLE (Direct)
// ============================================

// COMP001: NAFLD vs Control samples
MATCH (c:Comparison {sid: "COMP001"}), (s:Sample {sid: "SAMPLE001"})
MERGE (c)-[:INCLUDES_CASE]->(s);
MATCH (c:Comparison {sid: "COMP001"}), (s:Sample {sid: "SAMPLE005"})
MERGE (c)-[:INCLUDES_CASE]->(s);
MATCH (c:Comparison {sid: "COMP001"}), (s:Sample {sid: "SAMPLE002"})
MERGE (c)-[:INCLUDES_CONTROL]->(s);

// COMP002: T2D vs Control samples
MATCH (c:Comparison {sid: "COMP002"}), (s:Sample {sid: "SAMPLE003"})
MERGE (c)-[:INCLUDES_CASE]->(s);
MATCH (c:Comparison {sid: "COMP002"}), (s:Sample {sid: "SAMPLE004"})
MERGE (c)-[:INCLUDES_CONTROL]->(s);

// COMP003: MetSyn vs Control samples
MATCH (c:Comparison {sid: "COMP003"}), (s:Sample {sid: "SAMPLE006"})
MERGE (c)-[:INCLUDES_CASE]->(s);
MATCH (c:Comparison {sid: "COMP003"}), (s:Sample {sid: "SAMPLE007"})
MERGE (c)-[:INCLUDES_CONTROL]->(s);

// COMP006: Phenotype-stratified (Insulin Resistant)
MATCH (c:Comparison {sid: "COMP006"}), (s:Sample)-[:HAS_PHENOTYPE]->(ph:EFO {sid: "EFO:0004220"})
MERGE (c)-[:INCLUDES_CASE]->(s);
MATCH (c:Comparison {sid: "COMP006"}), (s:Sample)
WHERE NOT (s)-[:HAS_PHENOTYPE]->(:EFO {sid: "EFO:0004220"})
  AND s.condition = "Healthy"
MERGE (c)-[:INCLUDES_CONTROL]->(s);

// ============================================
// RELATIONSHIPS: COMPARISON -> DISEASE
// ============================================

MATCH (c:Comparison {sid: "COMP001"}), (d:Disease {sid: "MONDO:0005359"})
MERGE (c)-[:STUDIES_DISEASE]->(d);

MATCH (c:Comparison {sid: "COMP002"}), (d:Disease {sid: "MONDO:0005015"})
MERGE (c)-[:STUDIES_DISEASE]->(d);

MATCH (c:Comparison {sid: "COMP003"}), (d:Disease {sid: "MONDO:0011382"})
MERGE (c)-[:STUDIES_DISEASE]->(d);

MATCH (c:Comparison {sid: "COMP004"}), (d:Disease {sid: "MONDO:0005359"})
MERGE (c)-[:STUDIES_DISEASE]->(d);
MATCH (c:Comparison {sid: "COMP004"}), (d:Disease {sid: "MONDO:0005015"})
MERGE (c)-[:STUDIES_DISEASE]->(d);

// Meta-analysis
MATCH (c:Comparison {sid: "COMP008"}), (d:Disease {sid: "MONDO:0005359"})
MERGE (c)-[:STUDIES_DISEASE]->(d);
MATCH (c:Comparison {sid: "COMP008"}), (d:Disease {sid: "MONDO:0005015"})
MERGE (c)-[:STUDIES_DISEASE]->(d);
MATCH (c:Comparison {sid: "COMP008"}), (d:Disease {sid: "MONDO:0011382"})
MERGE (c)-[:STUDIES_DISEASE]->(d);

// ============================================
// RELATIONSHIPS: EXPERIMENT -> GENE (with expression)
// ============================================

// EXP001 - NAFLD signature
MATCH (e:Experiment {sid: "EXP001"}), (g:Gene {symbol: "PIK3CG"})
MERGE (e)-[:HAS_VALUE {logFC: 2.5, pValue: 0.001, regulated: "up", baseMean: 1250.3}]->(g);

MATCH (e:Experiment {sid: "EXP001"}), (g:Gene {symbol: "CXCL10"})
MERGE (e)-[:HAS_VALUE {logFC: 3.2, pValue: 0.0005, regulated: "up", baseMean: 890.5}]->(g);

MATCH (e:Experiment {sid: "EXP001"}), (g:Gene {symbol: "CD36"})
MERGE (e)-[:HAS_VALUE {logFC: 2.8, pValue: 0.0008, regulated: "up", baseMean: 3200.1}]->(g);

MATCH (e:Experiment {sid: "EXP001"}), (g:Gene {symbol: "ALB"})
MERGE (e)-[:HAS_VALUE {logFC: -1.5, pValue: 0.02, regulated: "down", baseMean: 45000.8}]->(g);

// EXP002 - T2D signature
MATCH (e:Experiment {sid: "EXP002"}), (g:Gene {symbol: "MTOR"})
MERGE (e)-[:HAS_VALUE {logFC: -1.8, pValue: 0.01, regulated: "down", baseMean: 1580.2}]->(g);

MATCH (e:Experiment {sid: "EXP002"}), (g:Gene {symbol: "AKT1"})
MERGE (e)-[:HAS_VALUE {logFC: 2.1, pValue: 0.002, regulated: "up", baseMean: 2100.4}]->(g);

MATCH (e:Experiment {sid: "EXP002"}), (g:Gene {symbol: "PPARG"})
MERGE (e)-[:HAS_VALUE {logFC: -2.3, pValue: 0.0003, regulated: "down", baseMean: 980.6}]->(g);

MATCH (e:Experiment {sid: "EXP002"}), (g:Gene {symbol: "CXCL8"})
MERGE (e)-[:HAS_VALUE {logFC: 2.9, pValue: 0.0006, regulated: "up", baseMean: 1340.2}]->(g);

// EXP003 - Metabolic Syndrome signature
MATCH (e:Experiment {sid: "EXP003"}), (g:Gene {symbol: "CD36"})
MERGE (e)-[:HAS_VALUE {logFC: 3.5, pValue: 0.0001, regulated: "up", baseMean: 2890.7}]->(g);

MATCH (e:Experiment {sid: "EXP003"}), (g:Gene {symbol: "PIK3CG"})
MERGE (e)-[:HAS_VALUE {logFC: 1.9, pValue: 0.004, regulated: "up", baseMean: 1100.3}]->(g);

// ============================================
// RELATIONSHIPS: EXPERIMENT -> PROTEIN (Proteomics data)
// ============================================

// EXP004 - NAFLD Proteomics (TMT-MS)
MATCH (e:Experiment {sid: "EXP004"}), (p:Protein {sid: "P48736"})
MERGE (e)-[:HAS_VALUE {
  logFC: -2.3,
  pValue: 0.002,
  regulated: "down",
  intensity: 2.5e7,
  peptides: 12,
  coverage: 45.2
}]->(p);

MATCH (e:Experiment {sid: "EXP004"}), (p:Protein {sid: "P16671"})
MERGE (e)-[:HAS_VALUE {
  logFC: 3.1,
  pValue: 0.0003,
  regulated: "up",
  intensity: 5.8e7,
  peptides: 18,
  coverage: 62.1
}]->(p);

MATCH (e:Experiment {sid: "EXP004"}), (p:Protein {sid: "P02778"})
MERGE (e)-[:HAS_VALUE {
  logFC: 2.8,
  pValue: 0.0008,
  regulated: "up",
  intensity: 1.2e6,
  peptides: 8,
  coverage: 38.5
}]->(p);

MATCH (e:Experiment {sid: "EXP004"}), (p:Protein {sid: "P02768"})
MERGE (e)-[:HAS_VALUE {
  logFC: -1.6,
  pValue: 0.015,
  regulated: "down",
  intensity: 8.9e8,
  peptides: 35,
  coverage: 72.3
}]->(p);

MATCH (e:Experiment {sid: "EXP004"}), (p:Protein {sid: "P01375"})
MERGE (e)-[:HAS_VALUE {
  logFC: 2.5,
  pValue: 0.001,
  regulated: "up",
  intensity: 3.2e6,
  peptides: 6,
  coverage: 42.1
}]->(p);

MATCH (e:Experiment {sid: "EXP004"}), (p:Protein {sid: "P35354"})
MERGE (e)-[:HAS_VALUE {
  logFC: 3.4,
  pValue: 0.0002,
  regulated: "up",
  intensity: 4.5e6,
  peptides: 14,
  coverage: 56.8
}]->(p);

// EXP005 - T2D Proteomics (TMT-MS)
MATCH (e:Experiment {sid: "EXP005"}), (p:Protein {sid: "P42345"})
MERGE (e)-[:HAS_VALUE {
  logFC: -1.7,
  pValue: 0.012,
  regulated: "down",
  intensity: 1.8e7,
  peptides: 22,
  coverage: 38.2
}]->(p);

MATCH (e:Experiment {sid: "EXP005"}), (p:Protein {sid: "P31749"})
MERGE (e)-[:HAS_VALUE {
  logFC: 2.0,
  pValue: 0.003,
  regulated: "up",
  intensity: 2.1e7,
  peptides: 16,
  coverage: 52.4
}]->(p);

MATCH (e:Experiment {sid: "EXP005"}), (p:Protein {sid: "P37231"})
MERGE (e)-[:HAS_VALUE {
  logFC: -2.1,
  pValue: 0.0005,
  regulated: "down",
  intensity: 8.5e6,
  peptides: 11,
  coverage: 41.3
}]->(p);

MATCH (e:Experiment {sid: "EXP005"}), (p:Protein {sid: "P01308"})
MERGE (e)-[:HAS_VALUE {
  logFC: -3.2,
  pValue: 0.0001,
  regulated: "down",
  intensity: 5.2e5,
  peptides: 4,
  coverage: 48.6
}]->(p);

MATCH (e:Experiment {sid: "EXP005"}), (p:Protein {sid: "P48736"})
MERGE (e)-[:HAS_VALUE {
  logFC: 1.8,
  pValue: 0.008,
  regulated: "up",
  intensity: 1.9e7,
  peptides: 10,
  coverage: 43.7
}]->(p);

// EXP006 - Metabolic Syndrome Proteomics (Label-free)
MATCH (e:Experiment {sid: "EXP006"}), (p:Protein {sid: "P16671"})
MERGE (e)-[:HAS_VALUE {
  logFC: 4.2,
  pValue: 0.00005,
  regulated: "up",
  intensity: 7.8e7,
  peptides: 21,
  coverage: 68.9
}]->(p);

MATCH (e:Experiment {sid: "EXP006"}), (p:Protein {sid: "P48736"})
MERGE (e)-[:HAS_VALUE {
  logFC: 2.1,
  pValue: 0.002,
  regulated: "up",
  intensity: 2.8e7,
  peptides: 13,
  coverage: 47.2
}]->(p);

MATCH (e:Experiment {sid: "EXP006"}), (p:Protein {sid: "P37231"})
MERGE (e)-[:HAS_VALUE {
  logFC: -1.9,
  pValue: 0.006,
  regulated: "down",
  intensity: 6.5e6,
  peptides: 9,
  coverage: 38.1
}]->(p);

MATCH (e:Experiment {sid: "EXP006"}), (p:Protein {sid: "P01375"})
MERGE (e)-[:HAS_VALUE {
  logFC: 3.6,
  pValue: 0.0001,
  regulated: "up",
  intensity: 5.1e6,
  peptides: 7,
  coverage: 51.3
}]->(p);

// EXP007 - NAFLD DIA-PASEF Proteomics
MATCH (e:Experiment {sid: "EXP007"}), (p:Protein {sid: "P48736"})
MERGE (e)-[:HAS_VALUE {
  logFC: 2.4,
  pValue: 0.0015,
  regulated: "up",
  intensity: 3.2e7,
  peptides: 15,
  coverage: 51.8
}]->(p);

MATCH (e:Experiment {sid: "EXP007"}), (p:Protein {sid: "P16671"})
MERGE (e)-[:HAS_VALUE {
  logFC: 2.9,
  pValue: 0.0006,
  regulated: "up",
  intensity: 6.1e7,
  peptides: 19,
  coverage: 64.5
}]->(p);

MATCH (e:Experiment {sid: "EXP007"}), (p:Protein {sid: "P31749"})
MERGE (e)-[:HAS_VALUE {
  logFC: 1.7,
  pValue: 0.01,
  regulated: "up",
  intensity: 1.5e7,
  peptides: 12,
  coverage: 46.3
}]->(p);

MATCH (e:Experiment {sid: "EXP007"}), (p:Protein {sid: "P05067"})
MERGE (e)-[:HAS_VALUE {
  logFC: 1.4,
  pValue: 0.025,
  regulated: "up",
  intensity: 8.2e6,
  peptides: 24,
  coverage: 28.7
}]->(p);

MATCH (e:Experiment {sid: "EXP007"}), (p:Protein {sid: "P10636"})
MERGE (e)-[:HAS_VALUE {
  logFC: 1.6,
  pValue: 0.018,
  regulated: "up",
  intensity: 5.5e6,
  peptides: 11,
  coverage: 35.2
}]->(p);

MATCH (e:Experiment {sid: "EXP007"}), (p:Protein {sid: "P02768"})
MERGE (e)-[:HAS_VALUE {
  logFC: -1.5,
  pValue: 0.02,
  regulated: "down",
  intensity: 9.2e8,
  peptides: 38,
  coverage: 75.6
}]->(p);

// ============================================
// RELATIONSHIPS: COMPARISON -> GENE (DGE Results)
// ============================================

// COMP001 results (transcriptomics)
MATCH (c:Comparison {sid: "COMP001"}), (g:Gene {symbol: "PIK3CG"})
MERGE (c)-[:FOUND_DIFFERENTIAL {
  logFC: 2.5,
  pValue: 0.001,
  adjPValue: 0.015,
  regulated: "up",
  significance: "significant",
  data_type: "transcriptomics"
}]->(g);

MATCH (c:Comparison {sid: "COMP001"}), (g:Gene {symbol: "CXCL10"})
MERGE (c)-[:FOUND_DIFFERENTIAL {
  logFC: 3.2,
  pValue: 0.0005,
  adjPValue: 0.008,
  regulated: "up",
  significance: "significant",
  data_type: "transcriptomics"
}]->(g);

MATCH (c:Comparison {sid: "COMP001"}), (g:Gene {symbol: "CD36"})
MERGE (c)-[:FOUND_DIFFERENTIAL {
  logFC: 2.8,
  pValue: 0.0008,
  adjPValue: 0.012,
  regulated: "up",
  significance: "significant",
  data_type: "transcriptomics"
}]->(g);

// COMP001 results (proteomics)
MATCH (c:Comparison {sid: "COMP001"}), (p:Protein {sid: "P48736"})
MERGE (c)-[:FOUND_DIFFERENTIAL {
  logFC: 2.3,
  pValue: 0.002,
  adjPValue: 0.018,
  regulated: "up",
  significance: "significant",
  data_type: "proteomics"
}]->(p);

MATCH (c:Comparison {sid: "COMP001"}), (p:Protein {sid: "P16671"})
MERGE (c)-[:FOUND_DIFFERENTIAL {
  logFC: 3.1,
  pValue: 0.0003,
  adjPValue: 0.006,
  regulated: "up",
  significance: "significant",
  data_type: "proteomics"
}]->(p);

MATCH (c:Comparison {sid: "COMP001"}), (p:Protein {sid: "P02778"})
MERGE (c)-[:FOUND_DIFFERENTIAL {
  logFC: 2.8,
  pValue: 0.0008,
  adjPValue: 0.012,
  regulated: "up",
  significance: "significant",
  data_type: "proteomics"
}]->(p);

MATCH (c:Comparison {sid: "COMP001"}), (p:Protein {sid: "P01375"})
MERGE (c)-[:FOUND_DIFFERENTIAL {
  logFC: 2.5,
  pValue: 0.001,
  adjPValue: 0.015,
  regulated: "up",
  significance: "significant",
  data_type: "proteomics"
}]->(p);

// COMP002 results (transcriptomics)
MATCH (c:Comparison {sid: "COMP002"}), (g:Gene {symbol: "MTOR"})
MERGE (c)-[:FOUND_DIFFERENTIAL {
  logFC: -1.8,
  pValue: 0.01,
  adjPValue: 0.045,
  regulated: "down",
  significance: "significant",
  data_type: "transcriptomics"
}]->(g);

MATCH (c:Comparison {sid: "COMP002"}), (g:Gene {symbol: "AKT1"})
MERGE (c)-[:FOUND_DIFFERENTIAL {
  logFC: 2.1,
  pValue: 0.002,
  adjPValue: 0.018,
  regulated: "up",
  significance: "significant",
  data_type: "transcriptomics"
}]->(g);

// COMP002 results (proteomics)
MATCH (c:Comparison {sid: "COMP002"}), (p:Protein {sid: "P42345"})
MERGE (c)-[:FOUND_DIFFERENTIAL {
  logFC: -1.7,
  pValue: 0.012,
  adjPValue: 0.048,
  regulated: "down",
  significance: "significant",
  data_type: "proteomics"
}]->(p);

MATCH (c:Comparison {sid: "COMP002"}), (p:Protein {sid: "P31749"})
MERGE (c)-[:FOUND_DIFFERENTIAL {
  logFC: 2.0,
  pValue: 0.003,
  adjPValue: 0.022,
  regulated: "up",
  significance: "significant",
  data_type: "proteomics"
}]->(p);

MATCH (c:Comparison {sid: "COMP002"}), (p:Protein {sid: "P37231"})
MERGE (c)-[:FOUND_DIFFERENTIAL {
  logFC: -2.1,
  pValue: 0.0005,
  adjPValue: 0.008,
  regulated: "down",
  significance: "significant",
  data_type: "proteomics"
}]->(p);

// COMP008 - Meta-analysis (shared signatures across omics)
MATCH (c:Comparison {sid: "COMP008"}), (g:Gene {symbol: "PIK3CG"})
MERGE (c)-[:FOUND_DIFFERENTIAL {
  logFC: 2.2,
  pValue: 0.0001,
  adjPValue: 0.005,
  regulated: "up",
  significance: "significant",
  data_type: "meta_analysis",
  note: "Shared across NAFLD and MetSyn"
}]->(g);

MATCH (c:Comparison {sid: "COMP008"}), (p:Protein {sid: "P48736"})
MERGE (c)-[:FOUND_DIFFERENTIAL {
  logFC: 2.1,
  pValue: 0.0002,
  adjPValue: 0.006,
  regulated: "up",
  significance: "significant",
  data_type: "meta_analysis",
  note: "Consistent protein-level validation"
}]->(p);

// COMP009 - Multi-omics integration
MATCH (c:Comparison {sid: "COMP009"}), (g:Gene {symbol: "PIK3CG"})
MERGE (c)-[:FOUND_DIFFERENTIAL {
  logFC: 2.5,
  pValue: 0.001,
  adjPValue: 0.015,
  regulated: "up",
  significance: "significant",
  data_type: "transcriptomics",
  correlation: 0.85
}]->(g);

MATCH (c:Comparison {sid: "COMP009"}), (p:Protein {sid: "P48736"})
MERGE (c)-[:FOUND_DIFFERENTIAL {
  logFC: 2.35,
  pValue: 0.0018,
  adjPValue: 0.017,
  regulated: "up",
  significance: "significant",
  data_type: "proteomics",
  correlation: 0.85
}]->(p);

MATCH (c:Comparison {sid: "COMP009"}), (g:Gene {symbol: "CD36"})
MERGE (c)-[:FOUND_DIFFERENTIAL {
  logFC: 2.8,
  pValue: 0.0008,
  adjPValue: 0.012,
  regulated: "up",
  significance: "significant",
  data_type: "transcriptomics",
  correlation: 0.92
}]->(g);

MATCH (c:Comparison {sid: "COMP009"}), (p:Protein {sid: "P16671"})
MERGE (c)-[:FOUND_DIFFERENTIAL {
  logFC: 3.0,
  pValue: 0.0005,
  adjPValue: 0.008,
  regulated: "up",
  significance: "significant",
  data_type: "proteomics",
  correlation: 0.92
}]->(p);

// ============================================
// RELATIONSHIPS: GENE -> PROTEIN
// ============================================

MATCH (g:Gene {symbol: "PIK3CG"}), (p:Protein {sid: "P48736"})
MERGE (g)-[:CODES]->(p);
MATCH (g:Gene {symbol: "CXCL10"}), (p:Protein {sid: "P02778"})
MERGE (g)-[:CODES]->(p);
MATCH (g:Gene {symbol: "MTOR"}), (p:Protein {sid: "P42345"})
MERGE (g)-[:CODES]->(p);
MATCH (g:Gene {symbol: "AKT1"}), (p:Protein {sid: "P31749"})
MERGE (g)-[:CODES]->(p);
MATCH (g:Gene {symbol: "PPARG"}), (p:Protein {sid: "P37231"})
MERGE (g)-[:CODES]->(p);
MATCH (g:Gene {symbol: "CD36"}), (p:Protein {sid: "P16671"})
MERGE (g)-[:CODES]->(p);
MATCH (g:Gene {symbol: "ALB"}), (p:Protein {sid: "P02768"})
MERGE (g)-[:CODES]->(p);

// ============================================
// RELATIONSHIPS: GENE -> ID
// ============================================

MATCH (g:Gene {symbol: "PIK3CG"}), (id:ID {sid: "5294"})
MERGE (g)-[:MAPPED]->(id);
MATCH (g:Gene {symbol: "CXCL10"}), (id:ID {sid: "3627"})
MERGE (g)-[:MAPPED]->(id);
MATCH (g:Gene {symbol: "MTOR"}), (id:ID {sid: "2475"})
MERGE (g)-[:MAPPED]->(id);
MATCH (g:Gene {symbol: "AKT1"}), (id:ID {sid: "207"})
MERGE (g)-[:MAPPED]->(id);
MATCH (g:Gene {symbol: "PPARG"}), (id:ID {sid: "5468"})
MERGE (g)-[:MAPPED]->(id);

// ============================================
// RELATIONSHIPS: GENE -> DISEASE
// ============================================

MATCH (g:Gene {symbol: "PIK3CG"}), (d:Disease {sid: "MONDO:0005359"})
MERGE (g)-[:RELATED_TO {source: "DisGeNET", score: 0.75}]->(d);

MATCH (g:Gene {symbol: "PPARG"}), (d:Disease {sid: "MONDO:0005015"})
MERGE (g)-[:RELATED_TO {source: "OpenTargets", score: 0.85}]->(d);

MATCH (g:Gene {symbol: "MTOR"}), (d:Disease {sid: "MONDO:0005015"})
MERGE (g)-[:RELATED_TO {source: "DisGeNET", score: 0.68}]->(d);

MATCH (g:Gene {symbol: "CD36"}), (d:Disease {sid: "MONDO:0011382"})
MERGE (g)-[:RELATED_TO {source: "OpenTargets", score: 0.72}]->(d);

MATCH (g:Gene {symbol: "AKT1"}), (d:Disease {sid: "MONDO:0005015"})
MERGE (g)-[:RELATED_TO {source: "DisGeNET", score: 0.81}]->(d);

// ============================================
// RELATIONSHIPS: PROTEIN -> GO
// ============================================

MATCH (p:Protein {sid: "P48736"}), (go:GO {sid: "GO:0008286"})
MERGE (p)-[:ASSOCIATED_WITH {source: "GO"}]->(go);

MATCH (p:Protein {sid: "P02778"}), (go:GO {sid: "GO:0006954"})
MERGE (p)-[:ASSOCIATED_WITH {source: "GO"}]->(go);

MATCH (p:Protein {sid: "P42345"}), (go:GO {sid: "GO:0008286"})
MERGE (p)-[:ASSOCIATED_WITH {source: "GO"}]->(go);

MATCH (p:Protein {sid: "P31749"}), (go:GO {sid: "GO:0008286"})
MERGE (p)-[:ASSOCIATED_WITH {source: "GO"}]->(go);

MATCH (p:Protein {sid: "P37231"}), (go:GO {sid: "GO:0005158"})
MERGE (p)-[:ASSOCIATED_WITH {source: "GO"}]->(go);

MATCH (p:Protein {sid: "P16671"}), (go:GO {sid: "GO:0006629"})
MERGE (p)-[:ASSOCIATED_WITH {source: "GO"}]->(go);

MATCH (p:Protein {sid: "P02768"}), (go:GO {sid: "GO:0006955"})
MERGE (p)-[:ASSOCIATED_WITH {source: "GO"}]->(go);

// Additional GO term associations for pathway enrichment
MATCH (p:Protein {sid: "P48736"}), (go:GO {sid: "GO:0042593"})
MERGE (p)-[:ASSOCIATED_WITH {source: "GO"}]->(go);

MATCH (p:Protein {sid: "P31749"}), (go:GO {sid: "GO:0042593"})
MERGE (p)-[:ASSOCIATED_WITH {source: "GO"}]->(go);

MATCH (p:Protein {sid: "P42345"}), (go:GO {sid: "GO:0042593"})
MERGE (p)-[:ASSOCIATED_WITH {source: "GO"}]->(go);

MATCH (p:Protein {sid: "P37231"}), (go:GO {sid: "GO:0006629"})
MERGE (p)-[:ASSOCIATED_WITH {source: "GO"}]->(go);

MATCH (p:Protein {sid: "P16671"}), (go:GO {sid: "GO:0006629"})
MERGE (p)-[:ASSOCIATED_WITH {source: "GO"}]->(go);

MATCH (p:Protein {sid: "P01375"}), (go:GO {sid: "GO:0071356"})
MERGE (p)-[:ASSOCIATED_WITH {source: "GO"}]->(go);

MATCH (p:Protein {sid: "P35354"}), (go:GO {sid: "GO:0071356"})
MERGE (p)-[:ASSOCIATED_WITH {source: "GO"}]->(go);

MATCH (p:Protein {sid: "P02778"}), (go:GO {sid: "GO:0071356"})
MERGE (p)-[:ASSOCIATED_WITH {source: "GO"}]->(go);

MATCH (p:Protein {sid: "P01308"}), (go:GO {sid: "GO:0006006"})
MERGE (p)-[:ASSOCIATED_WITH {source: "GO"}]->(go);

MATCH (p:Protein {sid: "P01308"}), (go:GO {sid: "GO:0042593"})
MERGE (p)-[:ASSOCIATED_WITH {source: "GO"}]->(go);

MATCH (p:Protein {sid: "P37231"}), (go:GO {sid: "GO:0030154"})
MERGE (p)-[:ASSOCIATED_WITH {source: "GO"}]->(go);

MATCH (p:Protein {sid: "P37231"}), (go:GO {sid: "GO:0051091"})
MERGE (p)-[:ASSOCIATED_WITH {source: "GO"}]->(go);

// ============================================
// RELATIONSHIPS: GO -> PATHWAY (IS_PART_OF hierarchy)
// ============================================

// Insulin signaling GO terms to Pathways
MATCH (go:GO {sid: "GO:0008286"}), (pw:Pathway {sid: "KEGG:04910"})
MERGE (go)-[:IS_PART_OF]->(pw);

MATCH (go:GO {sid: "GO:0005158"}), (pw:Pathway {sid: "KEGG:04910"})
MERGE (go)-[:IS_PART_OF]->(pw);

MATCH (go:GO {sid: "GO:0042593"}), (pw:Pathway {sid: "KEGG:04910"})
MERGE (go)-[:IS_PART_OF]->(pw);

MATCH (go:GO {sid: "GO:0008286"}), (pw:Pathway {sid: "REACTOME:R-HSA-74751"})
MERGE (go)-[:IS_PART_OF]->(pw);

// PI3K-Akt pathway connections
MATCH (go:GO {sid: "GO:0008286"}), (pw:Pathway {sid: "KEGG:04151"})
MERGE (go)-[:IS_PART_OF]->(pw);

MATCH (go:GO {sid: "GO:0042593"}), (pw:Pathway {sid: "KEGG:04151"})
MERGE (go)-[:IS_PART_OF]->(pw);

MATCH (go:GO {sid: "GO:0043066"}), (pw:Pathway {sid: "KEGG:04151"})
MERGE (go)-[:IS_PART_OF]->(pw);

// mTOR pathway connections
MATCH (go:GO {sid: "GO:0042593"}), (pw:Pathway {sid: "KEGG:04150"})
MERGE (go)-[:IS_PART_OF]->(pw);

// Inflammatory pathway connections
MATCH (go:GO {sid: "GO:0006954"}), (pw:Pathway {sid: "KEGG:04064"})
MERGE (go)-[:IS_PART_OF]->(pw);

MATCH (go:GO {sid: "GO:0071356"}), (pw:Pathway {sid: "KEGG:04064"})
MERGE (go)-[:IS_PART_OF]->(pw);

MATCH (go:GO {sid: "GO:0006954"}), (pw:Pathway {sid: "WIKIPATHWAYS:WP1471"})
MERGE (go)-[:IS_PART_OF]->(pw);

MATCH (go:GO {sid: "GO:0071356"}), (pw:Pathway {sid: "WIKIPATHWAYS:WP1471"})
MERGE (go)-[:IS_PART_OF]->(pw);

MATCH (go:GO {sid: "GO:0006955"}), (pw:Pathway {sid: "WIKIPATHWAYS:WP1471"})
MERGE (go)-[:IS_PART_OF]->(pw);

// Lipid metabolism pathways
MATCH (go:GO {sid: "GO:0006629"}), (pw:Pathway {sid: "KEGG:04920"})
MERGE (go)-[:IS_PART_OF]->(pw);

MATCH (go:GO {sid: "GO:0006629"}), (pw:Pathway {sid: "KEGG:03320"})
MERGE (go)-[:IS_PART_OF]->(pw);

// PPAR signaling
MATCH (go:GO {sid: "GO:0030154"}), (pw:Pathway {sid: "KEGG:03320"})
MERGE (go)-[:IS_PART_OF]->(pw);

MATCH (go:GO {sid: "GO:0051091"}), (pw:Pathway {sid: "KEGG:03320"})
MERGE (go)-[:IS_PART_OF]->(pw);

// Glucose metabolism
MATCH (go:GO {sid: "GO:0006006"}), (pw:Pathway {sid: "KEGG:04910"})
MERGE (go)-[:IS_PART_OF]->(pw);

MATCH (go:GO {sid: "GO:0006006"}), (pw:Pathway {sid: "KEGG:04920"})
MERGE (go)-[:IS_PART_OF]->(pw);

// Interleukin signaling
MATCH (go:GO {sid: "GO:0006954"}), (pw:Pathway {sid: "REACTOME:R-HSA-449147"})
MERGE (go)-[:IS_PART_OF]->(pw);

MATCH (go:GO {sid: "GO:0071356"}), (pw:Pathway {sid: "REACTOME:R-HSA-449147"})
MERGE (go)-[:IS_PART_OF]->(pw);

// ============================================
// RELATIONSHIPS: DISEASE -> PATHWAY (direct disease-pathway associations)
// ============================================

MATCH (d:Disease {sid: "MONDO:0005359"}), (pw:Pathway {sid: "KEGG:04920"})
MERGE (d)-[:INVOLVES_PATHWAY {evidence: "literature"}]->(pw);

MATCH (d:Disease {sid: "MONDO:0005359"}), (pw:Pathway {sid: "KEGG:03320"})
MERGE (d)-[:INVOLVES_PATHWAY {evidence: "literature"}]->(pw);

MATCH (d:Disease {sid: "MONDO:0005359"}), (pw:Pathway {sid: "KEGG:04151"})
MERGE (d)-[:INVOLVES_PATHWAY {evidence: "literature"}]->(pw);

MATCH (d:Disease {sid: "MONDO:0005015"}), (pw:Pathway {sid: "KEGG:04910"})
MERGE (d)-[:INVOLVES_PATHWAY {evidence: "literature"}]->(pw);

MATCH (d:Disease {sid: "MONDO:0005015"}), (pw:Pathway {sid: "KEGG:04151"})
MERGE (d)-[:INVOLVES_PATHWAY {evidence: "literature"}]->(pw);

MATCH (d:Disease {sid: "MONDO:0005015"}), (pw:Pathway {sid: "KEGG:04920"})
MERGE (d)-[:INVOLVES_PATHWAY {evidence: "literature"}]->(pw);

MATCH (d:Disease {sid: "MONDO:0011382"}), (pw:Pathway {sid: "KEGG:04920"})
MERGE (d)-[:INVOLVES_PATHWAY {evidence: "literature"}]->(pw);

MATCH (d:Disease {sid: "MONDO:0011382"}), (pw:Pathway {sid: "KEGG:04910"})
MERGE (d)-[:INVOLVES_PATHWAY {evidence: "literature"}]->(pw);

// ============================================
// RELATIONSHIPS: PROTEIN-PROTEIN INTERACTIONS
// ============================================

MATCH (p1:Protein {sid: "P48736"}), (p2:Protein {sid: "P31749"})
MERGE (p1)-[:INTERACTS_WITH {source: "STRING", score: 0.9}]->(p2);

MATCH (p1:Protein {sid: "P31749"}), (p2:Protein {sid: "P42345"})
MERGE (p1)-[:INTERACTS_WITH {source: "STRING", score: 0.95}]->(p2);

MATCH (p1:Protein {sid: "P31749"}), (p2:Protein {sid: "P37231"})
MERGE (p1)-[:INTERACTS_WITH {source: "STRING", score: 0.78}]->(p2);

MATCH (p1:Protein {sid: "P16671"}), (p2:Protein {sid: "P48736"})
MERGE (p1)-[:INTERACTS_WITH {source: "STRING", score: 0.65}]->(p2);

// Extended PPI network for neighborhood analysis
MATCH (p1:Protein {sid: "P48736"}), (p2:Protein {sid: "P42345"})
MERGE (p1)-[:INTERACTS_WITH {source: "STRING", score: 0.72, evidence: "experimental"}]->(p2);

MATCH (p1:Protein {sid: "P42345"}), (p2:Protein {sid: "P37231"})
MERGE (p1)-[:INTERACTS_WITH {source: "STRING", score: 0.81, evidence: "experimental"}]->(p2);

MATCH (p1:Protein {sid: "P31749"}), (p2:Protein {sid: "P01308"})
MERGE (p1)-[:INTERACTS_WITH {source: "STRING", score: 0.88, evidence: "experimental"}]->(p2);

MATCH (p1:Protein {sid: "P37231"}), (p2:Protein {sid: "P01308"})
MERGE (p1)-[:INTERACTS_WITH {source: "STRING", score: 0.76, evidence: "database"}]->(p2);

MATCH (p1:Protein {sid: "P16671"}), (p2:Protein {sid: "P31749"})
MERGE (p1)-[:INTERACTS_WITH {source: "STRING", score: 0.68, evidence: "experimental"}]->(p2);

MATCH (p1:Protein {sid: "P16671"}), (p2:Protein {sid: "P37231"})
MERGE (p1)-[:INTERACTS_WITH {source: "STRING", score: 0.55, evidence: "co-expression"}]->(p2);

MATCH (p1:Protein {sid: "P02778"}), (p2:Protein {sid: "P01375"})
MERGE (p1)-[:INTERACTS_WITH {source: "STRING", score: 0.82, evidence: "experimental"}]->(p2);

MATCH (p1:Protein {sid: "P01375"}), (p2:Protein {sid: "P35354"})
MERGE (p1)-[:INTERACTS_WITH {source: "STRING", score: 0.91, evidence: "experimental"}]->(p2);

MATCH (p1:Protein {sid: "P02778"}), (p2:Protein {sid: "P35354"})
MERGE (p1)-[:INTERACTS_WITH {source: "STRING", score: 0.73, evidence: "co-expression"}]->(p2);

MATCH (p1:Protein {sid: "P48736"}), (p2:Protein {sid: "P02768"})
MERGE (p1)-[:INTERACTS_WITH {source: "STRING", score: 0.42, evidence: "text-mining"}]->(p2);

MATCH (p1:Protein {sid: "P05067"}), (p2:Protein {sid: "P10636"})
MERGE (p1)-[:INTERACTS_WITH {source: "STRING", score: 0.85, evidence: "experimental"}]->(p2);

MATCH (p1:Protein {sid: "P31749"}), (p2:Protein {sid: "P05067"})
MERGE (p1)-[:INTERACTS_WITH {source: "STRING", score: 0.67, evidence: "database"}]->(p2);

MATCH (p1:Protein {sid: "P42345"}), (p2:Protein {sid: "P05067"})
MERGE (p1)-[:INTERACTS_WITH {source: "STRING", score: 0.71, evidence: "database"}]->(p2);

// Bidirectional interactions (making network undirected)
MATCH (p1:Protein {sid: "P31749"}), (p2:Protein {sid: "P48736"})
MERGE (p2)-[:INTERACTS_WITH {source: "STRING", score: 0.9}]->(p1);

MATCH (p1:Protein {sid: "P42345"}), (p2:Protein {sid: "P31749"})
MERGE (p2)-[:INTERACTS_WITH {source: "STRING", score: 0.95}]->(p1);

MATCH (p1:Protein {sid: "P37231"}), (p2:Protein {sid: "P31749"})
MERGE (p2)-[:INTERACTS_WITH {source: "STRING", score: 0.78}]->(p1);

MATCH (p1:Protein {sid: "P48736"}), (p2:Protein {sid: "P16671"})
MERGE (p2)-[:INTERACTS_WITH {source: "STRING", score: 0.65}]->(p1);

Cypher Queries

Below are some queries that can be used to get some insights from the data available.

Key Examples in the Dataset

These are just a few key examples within the dataset, and the queries that could be used to showcase them

NAFLD Concordant Overexpression (COMP001):

PIK3CG: mRNA +2.5 FC ↔ Protein +2.3 FC ✓ Concordant
CD36: mRNA +2.8 FC ↔ Protein +3.1 FC ✓ Concordant
CXCL10: mRNA +3.2 FC ↔ Protein +2.8 FC ✓ Concordant

WITH
  "COMP001" AS sid,
  0 AS logFCThreshold
MATCH (c:Comparison {sid: sid})-[fd1:FOUND_DIFFERENTIAL]->(g:Gene)-[:CODES]->(p:Protein)<-[fd2:FOUND_DIFFERENTIAL]-(c)
RETURN
  g.symbol AS Gene,
  g.name AS GeneName,
  fd1.logFC AS `mRNA Fold Change`,
  fd2.logFC AS `Protein Fold Change`,
  CASE WHEN fd1.logFC > logFCThreshold AND fd2.logFC > logFCThreshold THEN 'Concordant (Overexpression)'
       WHEN fd1.logFC < logFCThreshold AND fd2.logFC < logFCThreshold THEN 'Concordant (Underexpression)'
       ELSE 'Discordant' END AS Regulation;

T2D Concordant Overexpression (COMP002):

AKT1: mRNA +2.1 FC ↔ Protein +2.0 FC ✓ Concordant

WITH
  "COMP002" AS sid,
  0 AS logFCThreshold
MATCH
  (c:Comparison {sid: sid})-[fd1:FOUND_DIFFERENTIAL]->(g:Gene)-[:CODES]->(p:Protein)<-[fd2:FOUND_DIFFERENTIAL]-(c)
WHERE
  fd1.logFC > logFCThreshold AND fd2.logFC > logFCThreshold
RETURN
  g.symbol AS Gene,
  g.name AS GeneName,
  fd1.logFC AS `mRNA Fold Change`,
  fd2.logFC AS `Protein Fold Change`

Multi-omics Integration (COMP009):

Demonstrates correlation between transcript and protein levels with correlation coefficients (0.85-0.92)

MATCH (c:Comparison {sid: 'COMP009'})-[fd:FOUND_DIFFERENTIAL]->(p:Protein)
WHERE fd.correlation >= 0.85 AND fd.correlation <= 0.92
RETURN c,fd,p

Proteomics-only changes - Identify post-transcriptional regulation

Find proteins that change significantly without corresponding mRNA changes.

// Proteomics-only changes - Identify post-transcriptional regulation
WITH
  "Proteomics" AS experimentType,
  1.5 AS logFCThreshold,
  0.05 AS pValueThreshold
MATCH
  (exp:Experiment {type: experimentType})-[r:HAS_VALUE]->(protein:Protein),
  (protein)<-[:CODES]-(gene:Gene)<-[fd:FOUND_DIFFERENTIAL]-(comp:Comparison)-[:COMPARES]->(exp)
WHERE
  r.pValue < pValueThreshold AND abs(r.logFC) > logFCThreshold
  AND fd.regulated <> r.regulated
RETURN
  protein.name AS Protein,
  gene.symbol AS Gene,
  r.logFC AS logFC,
  r.pValue AS PValue,
  r.regulated AS Direction;

Which proteins/genes are associated with a given disease?

Starting with a disease of interest, what Genes and Proteins are implicated, and what biological processes those are associated with.

// Find proteins associated with a given disease (e.g., Non-alcoholic fatty liver disease)
WITH "Non-alcoholic fatty liver disease" AS diseaseName
MATCH (d:Disease {name: diseaseName})<-[:RELATED_TO]-(g:Gene)-[:CODES]->(p:Protein)-[:ASSOCIATED_WITH]->(go:GO)
RETURN
  g.symbol AS Gene,
  p.sid AS Protein,
  go.name AS `Biological Process`
ORDER BY Gene;

Which proteins/genes are associated with a given phenotype?

We can also start with a particular phenotype and find associated genes/proteins.

// Find genes from experiments on samples with specific phenotype (e.g., elevated triglycerides)
WITH "Elevated triglycerides" AS phenotypeName
MATCH (ph:EFO {name: phenotypeName})<-[:HAS_PHENOTYPE]-(s:Sample)-[:HAS_EXPERIMENT]->(e:Experiment)-[hv:HAS_VALUE]->(g:Gene)
WHERE hv.pValue < 0.05
RETURN
  g.symbol AS Gene,
  hv.logFC AS logFC,
  hv.pValue AS PValue
ORDER BY hv.pValue;

Which diseases or phenotypes are linked to a given gene/protein (i.e. what else might targeting this protein affect)?

Starting with a gene or protein of interest, what diseases are associated with it?

// Find diseases linked to a given gene/protein
WITH "PIK3CG" AS geneSymbol
MATCH (g:Gene {symbol: geneSymbol})-[:RELATED_TO]-(d:Disease)
RETURN d.name AS Disease
ORDER BY Disease;

Find phenotypes linked to a given gene/protein (i.e. what else might targeting this protein affect)?

Beginning with a Gene, find associated phenotypes from samples in experiments measuring that gene.

// Find phenotypes linked to a given gene/protein
WITH "PIK3CG" AS geneSymbol
MATCH (g:Gene {symbol: geneSymbol})<-[:HAS_VALUE]-(:Experiment)<-[:HAS_EXPERIMENT]-(:Sample)-[:HAS_PHENOTYPE]->(ph:EFO)
RETURN
  DISTINCT g.symbol AS Gene,
  ph.name AS Phenotype,
  ph.sid AS PhenotypeID;

Which genes are overexpressed at both the mRNA (transcript) and protein levels in a given disease?

Starting with a disease (e.g., Non-alcoholic fatty liver disease), find the genes that are upregulated at both transcript and protein levels.

// Which genes are overexpressed at both the mRNA (transcript) and protein levels in a given disease?
WITH
  "Non-alcoholic fatty liver disease" AS diseaseName,
  "up" AS regulationDirection
MATCH
  (disease:Disease {name: diseaseName}),
  (comp:Comparison)-[:STUDIES_DISEASE]->(disease),
  (comp)-[fd:FOUND_DIFFERENTIAL]->(gene:Gene)
WHERE fd.regulated = regulationDirection
RETURN
  DISTINCT gene.symbol AS Gene,
  gene.name AS GeneName,
  fd.logFC AS mRNA_logFC,
  fd.adjPValue AS mRNA_AdjPValue;

Which proteins are in the network neighborhood (e.g. interacting proteins, upstream regulators, downstream effectors) of a candidate Gene?

Starting with a Gene of interest (e.g. PIK3CG), find its direct interacting proteins, and the proteins upstream and downstream from it.

// Find direct interacting proteins for PIK3CG
WITH "PIK3CG" AS targetGeneSymbol
MATCH
  (g:Gene {symbol: targetGeneSymbol})-[:CODES]->(p:Protein)-[i:INTERACTS_WITH]-(neighbor:Protein)<-[:CODES]-(ng:Gene)
RETURN
  g.symbol AS TargetGene,
  ng.symbol AS NeighborGene,
  neighbor.sid AS NeighborProtein,
  i.score AS InteractionScore
ORDER BY i.score DESC;

Under-explored but potentially druggable targets close to disease nodes?

This query looks for proteins that are 1-2 hops away from known disease-associated nodes but are not yet annotated to drugs, indicating potential novel targets.

// Find proteins 1-2 hops away from known disease-associated nodes that aren't annotated to drugs
MATCH path = (d:Disease)<-[:RELATED_TO]-(g:Gene)-[:CODES]->(p:Protein)-[:INTERACTS_WITH*1..2]-(neighbor:Protein)<-[:CODES]-(ng:Gene)
WHERE NOT (p)-[:ASSOCIATED_WITH]->(:Drug)
RETURN
  g.symbol AS TargetGene,
  ng.symbol AS NeighborGene,
  neighbor.sid AS NeighborProtein,
  length(path) AS Distance
ORDER BY Distance;

Among candidate targets for a disease, which have the strongest support from multiple evidence types (genetics, expression, pathway involvement, literature, etc.)?

Starting with a Disease of interest, find novel candidate genes based on shared GO pathways with known disease-associated genes, filtering out any genes already linked to the disease.

// Find novel candidate genes for Type 2 Diabetes through shared GO pathways
// with known disease-associated genes
WITH "Type 2 Diabetes" AS diseaseName
MATCH
  (disease:Disease {name: diseaseName})<-[:RELATED_TO]-(known:Gene)-[:CODES]->(kp:Protein)-[:ASSOCIATED_WITH]->(go:GO),
  (go)<-[:ASSOCIATED_WITH]-(cp:Protein)<-[:CODES]-(candidate:Gene)
WHERE
  NOT (candidate)-[:RELATED_TO]->(disease)
  AND candidate <> known
WITH
  candidate, disease, count(DISTINCT go) AS sharedPathways, collect(DISTINCT go.name) AS pathways
WHERE sharedPathways >= 1  // Reduced from 2 to 1 due to smaller demo dataset
RETURN
  candidate.symbol AS `Novel Candidate`,
  candidate.name AS `Candidate Name`,
  sharedPathways AS `Shared Pathway Count`,
  pathways AS `Shared Pathways`
ORDER BY `Shared Pathways Count` DESC
LIMIT 10;

Which candidate targets are expressed (or dysregulated) in the relevant tissue / cell type / biological context for the disease?

In this query we look for genes that are co-expressed with known disease genes across multiple experiments. This is a way to identify genes that may be functionally related to disease processes.

// Find genes co-expressed with known disease genes across experiments
WITH
  0.05 AS pValueThreshold,
  2 AS minCoExpressionCount
MATCH (disease:Disease)<-[:RELATED_TO]-(known:Gene)<-[hv1:HAS_VALUE]-(experiment:Experiment)-[hv2:HAS_VALUE]->(candidate:Gene)
WHERE
  NOT (candidate)-[:RELATED_TO]->(disease)
  AND hv1.regulated = hv2.regulated
  AND hv1.pValue < pValueThreshold AND hv2.pValue < pValueThreshold
WITH
  candidate,
  disease,
  count(DISTINCT experiment) AS coExpressionCount
WHERE coExpressionCount >= minCoExpressionCount
RETURN
  candidate.symbol AS NovelCandidate,
  disease.name AS Disease,
  coExpressionCount AS TimesCoExpressed
ORDER BY coExpressionCount DESC;

Which proteins are in the network neighborhood of a candidate target?

Starting with a Gene of interest (e.g. PIK3CG), find its direct interacting proteins, and the Genes that code for those proteins.

// Which proteins are in the network neighborhood of a candidate target?
WITH "PIK3CG" AS targetGeneSymbol
MATCH
  (candidate:Gene {symbol: targetGeneSymbol})-[:CODES]->(p:Protein)-[i:INTERACTS_WITH]-(neighborProtein:Protein)<-[:CODES]-(neighbourGene:Gene)
RETURN
  candidate.symbol AS `Candidate Gene`,
  neighbourGene.symbol AS `Neighbor Gene`,
  neighborProtein.sid AS `Neighbor Protein`,
  i.score AS `Interaction Score`
ORDER BY `Interaction Score` DESC;

What are the protein-protein interactions in 1-2 hops of my overexpressed genes from my RNA-seq?

We’re looking for Protein interactions starting from a specific overexpressed Gene (e.g., PIK3CG) identified in RNA-seq data, and exploring its interaction network up to 2 hops away, focusing on other proteins coded by overexpressed genes allowing us to potentially target not just the primary gene product but also its immediate network.

// What are the protein-protein interactions in 1–2 hops of my overexpressed genes from my RNA-seq?
WITH
  "PIK3CG" AS geneSymbol,
  0 AS logFCThreshold
MATCH
  path=(:Comparison)-[fd1:FOUND_DIFFERENTIAL]->(gene:Gene {symbol: geneSymbol})-[:CODES]->(p:Protein)-[i:INTERACTS_WITH*1..2]-(neighbor:Protein)<-[:CODES]-(neighbourGene:Gene)<-[fd2:FOUND_DIFFERENTIAL]-(:Comparison)
WHERE
  fd1.logFC > logFCThreshold AND fd2.logFC > logFCThreshold
RETURN
  gene.symbol AS TargetGene,
  neighbourGene.symbol AS NeighborGene,
  neighbor.sid AS NeighborProtein,
  length(path) AS Distance
ORDER BY Distance;

Multi-omics correlation - genes with matching transcriptomics and proteomics changes

Starting with a specific Comparison, find genes that show concordant changes at both the mRNA and protein levels.

// Multi-omics correlation - genes with matching transcriptomics and proteomics changes
WITH
  "COMP001" AS comparisonSid,
  "significant" AS significanceLevel
MATCH
  (comp:Comparison {sid: comparisonSid})-[r1:FOUND_DIFFERENTIAL]->(gene:Gene),
  (gene)-[:CODES]->(protein:Protein)<-[r2:FOUND_DIFFERENTIAL]-(comp)
WHERE
  r1.significance = significanceLevel
  AND r2.significance = significanceLevel
  AND r1.regulated = r2.regulated
RETURN
  gene.symbol AS Gene,
  protein.name AS Protein,
  r1.logFC AS mRNA_LogFC,
  r2.logFC AS Protein_LogFC,
  r1.regulated AS Direction,
  abs(r1.logFC - r2.logFC) AS Correlation_Delta
ORDER BY Correlation_Delta;

Proteomics data quality metrics

Assess proteomics experiments quality based on coverage and peptide counts.

// Proteomics data quality metrics
WITH "Proteomics" AS type
MATCH
  (exp:Experiment {type: type})-[r:HAS_VALUE]->(protein:Protein)
WITH
  exp,
  count(protein) AS ProteinsDetected,
  avg(r.coverage) AS AvgCoverage,
  avg(r.peptides) AS AvgPeptides,
  avg(r.intensity) AS AvgIntensity
RETURN
  exp.sid AS Experiment,
  exp.platform AS Platform,
  exp.method AS Method,
  ProteinsDetected,
  round(AvgCoverage, 1) AS AvgCoverage_Percent,
  round(AvgPeptides, 1) AS AvgPeptides,
  round(AvgIntensity, 1) AS AvgIntensity
ORDER BY ProteinsDetected DESC;

Cross-platform proteomics comparison

Compare same proteins across different proteomics platforms. This allows us to see how consistent the measurements are across platforms, providing validation of findings.

// Cross-platform proteomics comparison
WITH
  "P48736" AS proteinSid,
  "Proteomics" AS experimentType
MATCH (exp:Experiment {type: experimentType})-[r:HAS_VALUE]->(p:Protein {sid: proteinSid})
RETURN
  p.name AS Protein,
  exp.sid AS Experiment,
  exp.platform AS Platform,
  exp.method AS Method,
  r.logFC AS logFC,
  r.pValue AS PValue,
  r.peptides AS Peptides,
  r.coverage AS Coverage
ORDER BY exp.sid;

Multi-omics integration pathway analysis

Find GO pathways enriched across both transcriptomics and proteomics

// MATCH (comp:Comparison {sid: "COMP009"})-[:FOUND_DIFFERENTIAL]->(gene:Gene)
WITH 2 AS geneCount
MATCH (gene)-[:CODES]->(protein:Protein)-[:ASSOCIATED_WITH]->(go:GO)
WITH
  go,
  count(DISTINCT gene) AS GeneCount,
  collect(DISTINCT gene.symbol) AS Genes
WHERE GeneCount >= geneCount
RETURN
  go.name AS Pathway,
  go.sid AS goId,
  GeneCount AS GenesInPathway,
  Genes
ORDER BY GeneCount DESC;

Genes overexpressed at both mRNA and protein levels give a disease-specific signature

We start with a specific Disease (this time via it’s MONDO ID) that is being studied via a Comparison. From that Comparison find genes that are upregulated at both the transcript and protein levels.

This is useful to identify robust disease signatures that are supported by multiple layers of omics data, and provide high-confidence targets for further investigation.

WITH
  "MONDO:0005359" AS diseaseSid,  // Non-alcoholic fatty liver disease
  "up" AS regulationDirection,
  "transcriptomics" AS rnaDataType,
  "proteomics" AS proteomicsDataType
MATCH
  (disease:Disease {sid: diseaseSid})<-[:STUDIES_DISEASE]-(comp:Comparison)-[rnaR:FOUND_DIFFERENTIAL]->(gene:Gene)
WHERE rnaR.regulated = regulationDirection AND rnaR.data_type = rnaDataType
MATCH
  (gene)-[:CODES]->(protein:Protein)<-[protR:FOUND_DIFFERENTIAL]-(comp)
WHERE protR.regulated = regulationDirection AND protR.data_type = proteomicsDataType
RETURN
  disease.name AS Disease,
  gene.symbol AS Gene,
  rnaR.logFC AS Transcript_FC,
  protR.logFC AS Protein_FC,
  (rnaR.logFC + protR.logFC) / 2.0 AS Avg_logFC,
  round(abs(rnaR.logFC - protR.logFC), 2) AS mRNA_Protein_Correlation_Delta
ORDER BY Avg_logFC DESC;

Druggable proteins in the PPI neighborhood

Find proteins that are druggable and in the PPI neighbourhood of overexpressed genes (RNA-seq). This is important because even if your target protein isn’t druggable - its interaction partners might be, providing alternative therapeutic strategies.

WITH
  "EXP001" AS experimentSid,
  "RNA-seq" AS experimentType,
  "up" AS regulationDirection,
  0.05 AS pValueThreshold
MATCH
  (exp:Experiment {sid: experimentSid, type: experimentType})-[r:HAS_VALUE]->(gene:Gene)
WHERE
  r.regulated = regulationDirection AND r.pValue < pValueThreshold
MATCH
  (gene)-[:CODES]->(protein:Protein)-[:INTERACTS_WITH*1..2]-(neighbor:Protein)<-[:CODES]-(neighborGene:Gene)
OPTIONAL MATCH
  (neighborGene)-[:RELATED_TO]->(disease:Disease)
WITH
  DISTINCT neighbor,
  count(DISTINCT disease) AS `Disease Associations`,
  collect(DISTINCT disease.name) AS `Associated Diseases`
WHERE
  `Disease Associations` > 0
RETURN
  neighbor.name AS `Potential Drug Target`,
  neighbor.sid AS `UniProt Identifier`,
  `Disease Associations`,
  `Associated Diseases`
ORDER BY `Disease Associations` DESC;

Provenance and confidence of evidence for a target?

Starting with a Gene of interest (e.g. PIK3CG), find all supporting evidence from literature, expression data, and pathway associations, along with confidence scores where available.

// Get all evidence and provenance for PIK3CG
WITH "PIK3CG" AS geneSymbol
MATCH (g:Gene {symbol: geneSymbol})
OPTIONAL MATCH (g)-[r1:RELATED_TO]->(d:Disease)
OPTIONAL MATCH (g)<-[hv:HAS_VALUE]-(e:Experiment)<-[:COMPARES]-(c:Comparison)
OPTIONAL MATCH (g)-[:CODES]->(p:Protein)-[r2:ASSOCIATED_WITH]->(go:GO)
RETURN
  g.symbol AS Gene,
  collect(DISTINCT {
    source: r1.source,
    disease: d.name,
    confidence: r1.score
  }) AS `Literature Evidence`,
  collect(DISTINCT {
    experiment: e.sid,
    comparison: c.name,
    logFC: hv.logFC,
    pValue: hv.pValue,
    regulation: hv.regulated
  }) AS `Expression Evidence`,
  collect(DISTINCT {
    source: r2.source,
    pathway: go.name,
    goId: go.sid
  }) AS `Pathway Evidence`;

Are there functional modules or sub-networks (pathways, protein complexes) enriched among disease-associated proteins that might be more robust therapeutic targets than single proteins?

These analyses can help identify key biological processes driving disease, and highlight potential intervention points that might be more effective than targeting individual proteins alone.

// Find pathways enriched for disease-associated proteins
MATCH
  (disease:Disease)<-[:RELATED_TO]-(:Gene)-[:CODES]->(p:Protein)-[:ASSOCIATED_WITH]->(go:GO)
WITH
  disease, go, COLLECT(DISTINCT p.name) AS proteins
MATCH
  (go)-[:IS_PART_OF]->(pathway:Pathway)
RETURN
  pathway.name AS Pathway,
  size(proteins) AS ProteinCount,
  proteins AS ProteinsInPathway
ORDER BY ProteinCount DESC;

// Find GO terms enriched among Type 2 Diabetes-associated genes
WITH
  "Type 2 Diabetes" AS diseaseName,
  2 AS geneCountThreshold
MATCH (d:Disease {name: diseaseName})-[:RELATED_TO]-(g:Gene)-[:CODES]->(p:Protein)-[:ASSOCIATED_WITH]-(go:GO)
WITH geneCountThreshold, go, count(DISTINCT g) AS geneCount
WHERE geneCount >= geneCountThreshold
RETURN
  go.sid AS GOTerm,
  go.name AS GOName,
  geneCount AS NumGenesInModule
ORDER BY geneCount DESC;

// Find interconnected protein complexes in disease
WITH "Type 2 Diabetes" AS diseaseName
MATCH
  path=(d:Disease {name: diseaseName})<-[:RELATED_TO]-(g1:Gene)-[:CODES]->(p1:Protein)-[:INTERACTS_WITH]-(p2:Protein)<-[:CODES]-(g2:Gene)-[:RELATED_TO]->(d)
RETURN
  g1.symbol AS Gene1,
  g2.symbol AS Gene2,
  p1.sid AS Protein1,
  p2.sid AS Protein2
LIMIT 20;

Find genes that share multiple GO terms with known disease genes but aren’t annotated to the disease

We’re looking to find novel candidate genes for a disease (e.g., Type 2 Diabetes) based on shared GO pathways with known disease-associated genes.

// Find genes that share multiple GO terms with known disease genes but aren't annotated to the disease
WITH
  "Type 2 Diabetes" AS diseaseName,
  2 AS minSharedPathways
MATCH
  (disease:Disease {name: diseaseName})<-[:RELATED_TO]-(known:Gene)-[:CODES]->(kp:Protein)-[:ASSOCIATED_WITH]->(go:GO),
  (go)<-[:ASSOCIATED_WITH]-(cp:Protein)<-[:CODES]-(candidate:Gene)
WHERE
  NOT (candidate)-[:RELATED_TO]->(disease)
  AND candidate <> known
WITH
  candidate, disease, minSharedPathways,
  count(DISTINCT go) AS sharedPathways,
  collect(DISTINCT go.name) AS pathways
WHERE sharedPathways >= minSharedPathways
RETURN
  candidate.symbol AS NovelCandidate,
  disease.name AS Disease,
  sharedPathways AS SharedPathwayCount,
  pathways AS SharedPathways