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 266

7 diseases · 10 shared-gene connections
7 Diseases
15 Unique genes
0.194 Avg. similarity score
Von willebrand disorder Most-connected disease (5 links)
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Disease Searched: platelet-type von Willebrand 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 ⇵
Von willebrand disorder 5 5 9
Bernard-soulier syndrome 3 3 5
Cerebral thrombosis 3 3 3
Intracranial thrombosis 3 3 5
hereditary von Willebrand disease 3 3 1
platelet-type von Willebrand disease 2 2 1
platelet-type bleeding disorder 8 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
VWF 5 / 7 Bernard-soulier syndrome, Cerebral thrombosis, hereditary von Willebrand disease, Intracranial thrombosis and 1 more
GP1BA 3 / 7 Bernard-soulier syndrome, platelet-type von Willebrand disease, Von willebrand disorder
PLAT 3 / 7 Cerebral thrombosis, Intracranial thrombosis, Von willebrand disorder
P2RY12 2 / 7 platelet-type bleeding disorder 8, Von willebrand disorder
SERPINC1 2 / 7 Cerebral thrombosis, Intracranial thrombosis
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 ⇵
Platelet activation
GP1BA, GP1BB, GP9, RASGRP2, VWF, GP6, P2RY12, ITGA2, ITGA2B
 KEGG 9 / 126 57.2× 5.47e-15 1.77e-12 ✓ sig.
Intrinsic Pathway of Fibrin Clot Formation
GP1BA, GP1BB, GP9, VWF, SERPINC1, F11
 Reactome 6 / 23 209× 1.20e-13 3.00e-11 ✓ sig.
Platelet Adhesion to exposed collagen
GP1BA, GP1BB, GP9, VWF, GP6
 Reactome 5 / 11 364× 6.64e-13 1.48e-10 ✓ sig.
ECM-receptor interaction
GP1BA, GP1BB, GP9, VWF, GP6, ITGA2, ITGA2B
 KEGG 7 / 89 63.0× 5.92e-12 1.12e-9 ✓ sig.
Platelet Aggregation (Plug Formation)
GP1BA, GP1BB, GP9, VWF
 Reactome 4 / 8 400× 1.10e-10 1.61e-8 ✓ sig.
GP1b-IX-V activation signalling
GP1BA, GP1BB, GP9, VWF
 Reactome 4 / 12 267× 7.75e-10 9.24e-8 ✓ sig.
Complement and coagulation cascades
VWF, PLAT, SERPINC1, F11, F3
 KEGG 5 / 88 45.5× 5.34e-8 3.99e-6 ✓ sig.
Hematopoietic cell lineage
GP1BA, GP1BB, GP9, ITGA2, ITGA2B
 KEGG 5 / 100 40.0× 1.02e-7 7.10e-6 ✓ sig.
Integrin signaling
RASGRP2, VWF, ITGA2B
 Reactome 3 / 23 104× 2.75e-6 1.25e-4 ✓ sig.
Integrin cell surface interactions
VWF, ITGA2, ITGA2B
 Reactome 3 / 81 29.7× 1.27e-4 2.80e-3 ✓ sig.
p130Cas linkage to MAPK signaling for integrins
VWF, ITGA2B
 Reactome 2 / 15 107× 1.51e-4 3.22e-3 ✓ sig.
GRB2:SOS provides linkage to MAPK signaling for Integrins
VWF, ITGA2B
 Reactome 2 / 15 107× 1.51e-4 3.22e-3 ✓ sig.
Signaling by high-kinase activity BRAF mutants
VWF, ITGA2B
 Reactome 2 / 36 44.5× 8.95e-4 1.29e-2 ✓ sig.
MAP2K and MAPK activation
VWF, ITGA2B
 Reactome 2 / 40 40.0× 1.10e-3 1.52e-2 ✓ sig.
Signaling by moderate kinase activity BRAF mutants
VWF, ITGA2B
 Reactome 2 / 47 34.1× 1.52e-3 1.94e-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 ⇵
blood coagulation
GP1BA, GP1BB, GP9, VWF, PLAT, SERPINC1, F11, F3, GP6, P2RY12, ITGA2
 GO:0007596 11 / 106 129× 1.54e-22 3.55e-19 ✓ sig.
hemostasis
GP1BA, GP1BB, GP9, VWF, SERPINC1, F11, F3, GP6, P2RY12
 GO:0007599 9 / 55 204× 4.11e-20 6.54e-17 ✓ sig.
platelet activation
GP1BA, GP1BB, VWF, GP6, P2RY12
 GO:0030168 5 / 69 90.3× 1.73e-9 3.66e-7 ✓ sig.
blood coagulation, intrinsic pathway
GP1BA, GP1BB, GP9
 GO:0007597 3 / 8 467× 2.34e-8 3.58e-6 ✓ sig.
regulation of blood coagulation
GP1BA, SERPINC1, F11
 GO:0030193 3 / 11 340× 6.88e-8 8.92e-6 ✓ sig.
positive regulation of platelet activation
GP1BA, GP1BB, GP9
 GO:0010572 3 / 13 287× 1.19e-7 1.43e-5 ✓ sig.
cell adhesion
GP1BA, GP1BB, GP9, VWF, CDH15, ITGA2, ITGA2B
 GO:0007155 7 / 665 13.1× 3.51e-7 3.57e-5 ✓ sig.
megakaryocyte development
GP1BA, GP1BB, GP9
 GO:0035855 3 / 23 162× 7.34e-7 6.59e-5 ✓ sig.
release of sequestered calcium ion into cytosol
GP1BA, GP1BB, GP9
 GO:0051209 3 / 48 77.9× 7.08e-6 4.10e-4 ✓ sig.
collagen-activated signaling pathway
GP6, ITGA2
 GO:0038065 2 / 6 415× 9.00e-6 4.99e-4 ✓ sig.
positive regulation of positive chemotaxis
F3, ITGA2
 GO:0050927 2 / 11 227× 3.29e-5 1.36e-3 ✓ sig.
plasminogen activation
PLAT, F11
 GO:0031639 2 / 12 208× 3.95e-5 1.56e-3 ✓ sig.
fibrinolysis
GP1BA, PLAT
 GO:0042730 2 / 19 131× 1.02e-4 3.18e-3 ✓ sig.
positive regulation of leukocyte migration
ITGA2, ITGA2B
 GO:0002687 2 / 19 131× 1.02e-4 3.18e-3 ✓ sig.
cell-substrate adhesion
VWF, ITGA2
 GO:0031589 2 / 25 99.7× 1.79e-4 4.81e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Cerebral thrombosis Intracranial thrombosis 0.500 3 1.64e-11 1.77e-10 ✓ sig.
Cerebral thrombosis Von willebrand disorder 0.182 2 9.11e-7 5.37e-6 ✓ sig.
Bernard-soulier syndrome Von willebrand disorder 0.154 2 3.03e-6 1.63e-5 ✓ sig.
Intracranial thrombosis Von willebrand disorder 0.154 2 3.03e-6 1.63e-5 ✓ sig.
Cerebral thrombosis hereditary von Willebrand disease 0.250 1 1.95e-4 5.35e-4 ✓ sig.
Bernard-soulier syndrome hereditary von Willebrand disease 0.167 1 3.25e-4 7.71e-4 ✓ sig.
Bernard-soulier syndrome platelet-type von Willebrand disease 0.167 1 3.25e-4 7.71e-4 ✓ sig.
hereditary von Willebrand disease Intracranial thrombosis 0.167 1 3.25e-4 7.71e-4 ✓ sig.
platelet-type bleeding disorder 8 Von willebrand disorder 0.100 1 5.84e-4 1.16e-3 ✓ sig.
platelet-type von Willebrand disease Von willebrand disorder 0.100 1 5.84e-4 1.16e-3 ✓ sig.