Disease Clusters?

Groups of diseases that share a large number of curated genes with each other, computed via label propagation over the shared-gene similarity graph. See also Shared-Gene Disease Pairs for pairwise comparisons.

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Cluster 126

10 diseases · 19 shared-gene connections
10 Diseases
45 Unique genes
0.189 Avg. similarity score
Vascular remodeling Most-connected disease (8 links)
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Disease Pinned (dragged)
Node size = connections within this cluster · edge thickness = similarity strength · hover an edge for its details · click a node to select it and show its pairs below (double-click or Ctrl/⌘-click opens the disease page) · drag a node to pin it in place · scroll/pinch to zoom.

Member diseases (most connected first ‐ the cluster's core)

Disease ⇵ Connections in cluster ⇵ Significant partners ⇵ Curated genes ⇵
Vascular remodeling 8 8 6
Cardiovascular abnormalities 5 5 11
Deafness-lymphedema-leukemia syndrome 5 5 1
GATA2 deficiency with susceptibility to MDS/AML 5 5 1
Gata2 deficiency 5 5 1
Primary graft dysfunction 5 5 4
Vasculitis 2 2 29
Whim syndrome 1 1 2
nephronophthisis 16 1 1 1
telangiectasia, hereditary hemorrhagic, type 2 1 1 1

Top shared genes (genes linked to 2+ member diseases)

Gene ⇵ Member diseases ⇵ Linked diseases
GATA2 7 / 10 Cardiovascular abnormalities, Deafness-lymphedema-leukemia syndrome, Gata2 deficiency, GATA2 deficiency with susceptibility to MDS/AML and 3 more
SENP1 3 / 10 Primary graft dysfunction, Vascular remodeling, Vasculitis
ACVRL1 2 / 10 telangiectasia, hereditary hemorrhagic, type 2, Vascular remodeling
AGT 2 / 10 Cardiovascular abnormalities, Vascular remodeling
ANKS6 2 / 10 Cardiovascular abnormalities, nephronophthisis 16
CXCR2 2 / 10 Vascular remodeling, Whim syndrome
What do these columns mean?
Connections in cluster
How many other members this disease has a shared-gene link to (the node size in the network above). The most-connected diseases are the cluster's core.
Significant partners
How many of those links are statistically significant (FDR q < 0.05).
Curated genes
Distinct curated genes linked to that disease in GeDiPNet.
Member diseases (Top shared genes)
How many of this cluster's diseases are linked to the gene, out of the cluster's total. Genes shared by many members are the most direct explanation of why they group together.
Overlap genes (x / y)
x = genes shared between this cluster and the pathway/GO term; y = that pathway/GO term's total gene count. A higher x relative to y (and to the cluster's own size) means a tighter biological match.
Cluster gene count
Total distinct genes across every disease in this cluster -- the "n" used in the significance test below.
Fold enrichment
Observed overlap divided by the overlap expected by chance, given the cluster's gene count, the pathway/term's size and the gene universe tested. 5× means five times more shared genes than random. Tells strong hits apart when q-values are all vanishingly small.
P-value / FDR q-value
Is this pathway/GO term's overlap with the cluster more than chance? Upper-tail hypergeometric test, Benjamini-Hochberg corrected across every tested pathway/term (prefer the q-value -- it accounts for testing many at once).
Shared genes (Pairs within this cluster)
Number of curated genes the two diseases in that row have in common.
Similarity score (Pairs within this cluster)
Jaccard-based gene overlap between the two specific diseases in that row -- same metric as the main Shared-Gene Disease Pairs page.

Enriched Pathways (why this cluster is grouped, biologically)

Pathway ⇵ Source ⇵ Overlap genes ⇵ Fold enrichment ⇵ P-value ⇵ FDR q-value ⇵
Pathways in cancer
AGT, EDN1, FGF8, NOS2, BCL2L11, CBL, COL4A2, IL12RB2, NFKBIA, CXCR4
 KEGG 10 / 533 5.0× 2.13e-5 6.30e-4 ✓ sig.
AGE-RAGE signaling pathway in diabetic complications
AGT, EDN1, VCAM1, COL4A2, NOS3
 KEGG 5 / 101 13.2× 3.56e-5 9.63e-4 ✓ sig.
Nitric oxide stimulates guanylate cyclase
NOS2, NOS3
 Reactome 2 / 3 178× 4.11e-5 1.09e-3 ✓ sig.
Cytokine-cytokine receptor interaction
ACVRL1, CXCR2, CCR3, IL12RB2, TSLP, CSF3, CXCR4
 KEGG 7 / 298 6.3× 1.09e-4 2.41e-3 ✓ sig.
Relaxin signaling pathway
EDN1, NOS2, COL4A2, NFKBIA, NOS3
 KEGG 5 / 130 10.3× 1.19e-4 2.57e-3 ✓ sig.
Human cytomegalovirus infection
CXCR2, CCR3, NFKBIA, PTK2B, HLA-A, CXCR4
 KEGG 6 / 226 7.1× 1.83e-4 3.66e-3 ✓ sig.
Chemokine signaling pathway
CXCR2, CCR3, NFKBIA, PTK2B, CXCR4
 KEGG 5 / 193 6.9× 7.38e-4 1.08e-2 ✓ sig.
Arginine and proline metabolism
NOS2, NOS3, P4HA2
 KEGG 3 / 50 16.0× 8.52e-4 1.20e-2 ✓ sig.
Malaria
SELP, VCAM1, CSF3
 KEGG 3 / 50 16.0× 8.52e-4 1.20e-2 ✓ sig.
TNF signaling pathway
EDN1, VCAM1, IRF1, NFKBIA
 KEGG 4 / 119 9.0× 9.98e-4 1.35e-2 ✓ sig.
Platelet degranulation
SELP, PLG, SERPINA1, SERPINA3
 Reactome 4 / 123 8.7× 1.13e-3 1.49e-2 ✓ sig.
Chemokine receptors bind chemokines
CXCR2, CCR3, CXCR4
 Reactome 3 / 59 13.6× 1.38e-3 1.73e-2 ✓ sig.
Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models
BCL2L11, CAST
 Reactome 2 / 16 33.4× 1.59e-3 1.93e-2 ✓ sig.
Calcium signaling pathway
FGF8, NOS2, NOS3, PTK2B, CXCR4
 KEGG 5 / 254 5.3× 2.49e-3 2.69e-2 ✓ sig.
Cell adhesion molecules
SELP, VCAM1, CTLA4, HLA-A
 KEGG 4 / 160 6.7× 2.96e-3 3.04e-2 ✓ sig.

Enriched GO Terms (Biological Process, a second line of biological evidence)

GO term ⇵ GO ID ⇵ Overlap genes ⇵ Fold enrichment ⇵ P-value ⇵ FDR q-value ⇵
heart development
ALPK3, ANKS6, EDN1, FGF8, FOXC2, KCNQ1, STRA6, ACVRL1, GJA1, CCM2
 GO:0007507 10 / 273 15.2× 7.64e-10 1.76e-7 ✓ sig.
response to lipopolysaccharide
EDN1, NOS2, SELP, VCAM1, IL12RB2, MPO, NFKBIA, NOS3
 GO:0032496 8 / 161 20.6× 4.19e-9 7.96e-7 ✓ sig.
blood vessel remodeling
AGT, FGF8, FOXC2, ACVRL1, NOS3
 GO:0001974 5 / 42 49.4× 5.13e-8 6.92e-6 ✓ sig.
kidney development
AGT, ANKS6, FGF8, FOXC2, STRA6, BCL2L11
 GO:0001822 6 / 146 17.1× 1.30e-6 1.02e-4 ✓ sig.
regulation of blood pressure
AGT, EDN1, KCNQ1, ACVRL1, NOS3
 GO:0008217 5 / 83 25.0× 1.63e-6 1.22e-4 ✓ sig.
blood vessel diameter maintenance
AGT, EDN1, FOXC2, NOS3
 GO:0097746 4 / 37 44.9× 1.83e-6 1.34e-4 ✓ sig.
cellular response to cytokine stimulus
CCR3, NFKBIA, CSF3, CXCR4
 GO:0071345 4 / 53 31.3× 7.88e-6 4.33e-4 ✓ sig.
negative regulation of myeloid cell differentiation
GATA2, NFKBIA, PTK2B
 GO:0045638 3 / 19 65.6× 1.23e-5 6.13e-4 ✓ sig.
inflammatory response
NOS2, SELP, VCAM1, CXCR2, CCR3, NFKBIA, SERPINA3, CXCR4
 GO:0006954 8 / 467 7.1× 1.37e-5 6.68e-4 ✓ sig.
chemokine-mediated signaling pathway
CXCR2, CCR3, PTK2B, CXCR4
 GO:0070098 4 / 64 26.0× 1.68e-5 7.83e-4 ✓ sig.
renal sodium ion absorption
AGT, EDN1, KCNQ1
 GO:0070294 3 / 21 59.3× 1.68e-5 7.85e-4 ✓ sig.
positive regulation of endothelial cell migration
AGT, EDN1, FOXC2, PTK2B
 GO:0010595 4 / 66 25.2× 1.90e-5 8.60e-4 ✓ sig.
positive regulation of cytosolic calcium ion concentration
EDN1, GATA2, CXCR2, CCR3, CXCR4
 GO:0007204 5 / 137 15.2× 1.90e-5 8.62e-4 ✓ sig.
in utero embryonic development
ANKS6, EDN1, ACVRL1, BCL2L11, CCM2, NOS3
 GO:0001701 6 / 252 9.9× 2.97e-5 1.21e-3 ✓ sig.
embryonic heart tube development
EDN1, FGF8, FOXC2
 GO:0035050 3 / 26 47.9× 3.26e-5 1.30e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Primary graft dysfunction Vascular remodeling 0.222 2 7.59e-7 4.79e-6 ✓ sig.
Cardiovascular abnormalities Vascular remodeling 0.125 2 6.95e-6 3.72e-5 ✓ sig.
Primary graft dysfunction Vasculitis 0.063 2 2.05e-5 1.03e-4 ✓ sig.
Deafness-lymphedema-leukemia syndrome Gata2 deficiency 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Deafness-lymphedema-leukemia syndrome GATA2 deficiency with susceptibility to MDS/AML 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Gata2 deficiency GATA2 deficiency with susceptibility to MDS/AML 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Vascular remodeling Vasculitis 0.059 2 5.11e-5 2.34e-4 ✓ sig.
Deafness-lymphedema-leukemia syndrome Primary graft dysfunction 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Gata2 deficiency Primary graft dysfunction 0.200 1 2.60e-4 6.40e-4 ✓ sig.
GATA2 deficiency with susceptibility to MDS/AML Primary graft dysfunction 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Deafness-lymphedema-leukemia syndrome Vascular remodeling 0.143 1 3.90e-4 8.52e-4 ✓ sig.
Gata2 deficiency Vascular remodeling 0.143 1 3.90e-4 8.52e-4 ✓ sig.
GATA2 deficiency with susceptibility to MDS/AML Vascular remodeling 0.143 1 3.90e-4 8.52e-4 ✓ sig.
telangiectasia, hereditary hemorrhagic, type 2 Vascular remodeling 0.143 1 3.90e-4 8.52e-4 ✓ sig.
Cardiovascular abnormalities Gata2 deficiency 0.083 1 7.14e-4 1.31e-3 ✓ sig.
Cardiovascular abnormalities nephronophthisis 16 0.083 1 7.14e-4 1.31e-3 ✓ sig.
Cardiovascular abnormalities GATA2 deficiency with susceptibility to MDS/AML 0.083 1 7.14e-4 1.31e-3 ✓ sig.
Cardiovascular abnormalities Deafness-lymphedema-leukemia syndrome 0.083 1 7.14e-4 1.31e-3 ✓ sig.
Vascular remodeling Whim syndrome 0.125 1 7.79e-4 1.39e-3 ✓ sig.