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 114

10 diseases · 20 shared-gene connections
10 Diseases
10 Unique genes
0.360 Avg. similarity score
Amyloid neuropathy Most-connected disease (7 links)
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Disease Searched: cerebral amyloid angiopathy, app-related 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 ⇵
Amyloid neuropathy 7 7 3
Abeta amyloidosis 5 5 1
Amyloid angiopathy 5 5 1
Eye manifestations 5 5 1
Partial epilepsy with variable foci 5 5 1
cerebral amyloid angiopathy, app-related 5 5 1
Acne inversa 4 4 3
Early onset alzheimers disease with behavioral disturbance 2 2 2
Dowling degos disease 1 1 5
Pash syndrome 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
APP 6 / 10 Abeta amyloidosis, Amyloid angiopathy, Amyloid neuropathy, cerebral amyloid angiopathy, app-related and 2 more
PSEN1 3 / 10 Acne inversa, Amyloid neuropathy, Early onset alzheimers disease with behavioral disturbance
NCSTN 2 / 10 Acne inversa, Pash syndrome
PSENEN 2 / 10 Acne inversa, Dowling degos disease
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 ⇵
NOTCH3 Activation and Transmission of Signal to the Nucleus
NCSTN, PSENEN, PSEN1, ADAM10
 Reactome 4 / 19 253× 9.34e-10 9.97e-8 ✓ sig.
Amyloid fiber formation
APP, NCSTN, PSENEN, TTR, ADAM10
 Reactome 5 / 109 55.1× 1.36e-8 1.08e-6 ✓ sig.
Noncanonical activation of NOTCH3
NCSTN, PSENEN, PSEN1
 Reactome 3 / 8 450× 2.32e-8 1.73e-6 ✓ sig.
Regulated proteolysis of p75NTR
NCSTN, PSENEN, PSEN1
 Reactome 3 / 11 328× 6.84e-8 4.55e-6 ✓ sig.
Constitutive Signaling by NOTCH1 PEST Domain Mutants
NCSTN, PSENEN, PSEN1, ADAM10
 Reactome 4 / 58 82.8× 1.01e-7 6.37e-6 ✓ sig.
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
NCSTN, PSENEN, PSEN1, ADAM10
 Reactome 4 / 58 82.8× 1.01e-7 6.37e-6 ✓ sig.
NRIF signals cell death from the nucleus
NCSTN, PSENEN, PSEN1
 Reactome 3 / 15 240× 1.88e-7 1.10e-5 ✓ sig.
Nuclear signaling by ERBB4
NCSTN, PSENEN, PSEN1
 Reactome 3 / 24 150× 8.34e-7 4.00e-5 ✓ sig.
Alzheimer disease
APP, NCSTN, PSENEN, PSEN1, ADAM10
 KEGG 5 / 388 15.5× 7.56e-6 2.57e-4 ✓ sig.
EPH-ephrin mediated repulsion of cells
NCSTN, PSENEN, PSEN1
 Reactome 3 / 50 72.1× 7.98e-6 2.69e-4 ✓ sig.
Notch signaling pathway
NCSTN, PSENEN, PSEN1
 KEGG 3 / 62 58.1× 1.53e-5 4.66e-4 ✓ sig.
Neutrophil degranulation
NCSTN, PSEN1, TTR, ADAM10
 Reactome 4 / 480 10.0× 4.37e-4 7.09e-3 ✓ sig.
Other types of O-glycan biosynthesis
POFUT1, POGLUT1
 KEGG 2 / 47 51.1× 6.61e-4 9.80e-3 ✓ sig.
Post-translational protein phosphorylation
APP, ADAM10
 Reactome 2 / 108 22.2× 3.44e-3 3.38e-2 ✓ sig.
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
APP, ADAM10
 Reactome 2 / 125 19.2× 4.58e-3 4.13e-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 ⇵
Notch signaling pathway
APP, NCSTN, PSENEN, PSEN1, ADAM10, POFUT1
 GO:0007219 6 / 117 95.8× 1.09e-11 3.97e-9 ✓ sig.
amyloid precursor protein catabolic process
NCSTN, PSENEN, PSEN1, ADAM10
 GO:0042987 4 / 14 534× 4.13e-11 1.32e-8 ✓ sig.
membrane protein ectodomain proteolysis
NCSTN, PSENEN, PSEN1, ADAM10
 GO:0006509 4 / 27 277× 7.21e-10 1.68e-7 ✓ sig.
Notch receptor processing
NCSTN, PSENEN, PSEN1
 GO:0007220 3 / 9 623× 9.25e-9 1.58e-6 ✓ sig.
amyloid-beta formation
NCSTN, PSENEN, PSEN1
 GO:0034205 3 / 10 561× 1.32e-8 2.16e-6 ✓ sig.
amyloid precursor protein metabolic process
NCSTN, PSENEN, PSEN1
 GO:0042982 3 / 12 467× 2.42e-8 3.63e-6 ✓ sig.
protein processing
NCSTN, PSENEN, PSEN1, ADAM10
 GO:0016485 4 / 95 78.7× 1.29e-7 1.48e-5 ✓ sig.
regulation of Notch signaling pathway
ADAM10, POFUT1, POGLUT1
 GO:0008593 3 / 23 244× 1.94e-7 2.11e-5 ✓ sig.
positive regulation of tumor necrosis factor production
APP, PSEN1, ADAM10, LRRK2
 GO:0032760 4 / 113 66.1× 2.59e-7 2.69e-5 ✓ sig.
protein catabolic process at postsynapse
PSEN1, ADAM10
 GO:0140249 2 / 3 1,246× 7.73e-7 6.69e-5 ✓ sig.
astrocyte activation involved in immune response
APP, PSEN1
 GO:0002265 2 / 4 934× 1.55e-6 1.19e-4 ✓ sig.
somitogenesis
PSEN1, POFUT1, POGLUT1
 GO:0001756 3 / 50 112× 2.13e-6 1.53e-4 ✓ sig.
positive regulation of amyloid fibril formation
APP, PSEN1
 GO:1905908 2 / 5 747× 2.58e-6 1.77e-4 ✓ sig.
cellular response to manganese ion
APP, LRRK2
 GO:0071287 2 / 7 534× 5.40e-6 3.22e-4 ✓ sig.
learning or memory
APP, NCSTN, PSEN1
 GO:0007611 3 / 72 77.9× 6.45e-6 3.72e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Amyloid angiopathy Eye manifestations 0.500 1 6.49e-5 2.33e-4 ✓ sig.
Eye manifestations Partial epilepsy with variable foci 0.500 1 6.49e-5 2.33e-4 ✓ sig.
cerebral amyloid angiopathy, app-related Eye manifestations 0.500 1 6.49e-5 2.33e-4 ✓ sig.
cerebral amyloid angiopathy, app-related Partial epilepsy with variable foci 0.500 1 6.49e-5 2.33e-4 ✓ sig.
Amyloid angiopathy cerebral amyloid angiopathy, app-related 0.500 1 6.49e-5 2.33e-4 ✓ sig.
Abeta amyloidosis Amyloid angiopathy 0.500 1 6.49e-5 2.33e-4 ✓ sig.
Amyloid angiopathy Partial epilepsy with variable foci 0.500 1 6.49e-5 2.33e-4 ✓ sig.
Abeta amyloidosis cerebral amyloid angiopathy, app-related 0.500 1 6.49e-5 2.33e-4 ✓ sig.
Abeta amyloidosis Eye manifestations 0.500 1 6.49e-5 2.33e-4 ✓ sig.
Abeta amyloidosis Partial epilepsy with variable foci 0.500 1 6.49e-5 2.33e-4 ✓ sig.
Acne inversa Pash syndrome 0.250 1 1.95e-4 5.35e-4 ✓ sig.
Abeta amyloidosis Amyloid neuropathy 0.250 1 1.95e-4 5.35e-4 ✓ sig.
Amyloid angiopathy Amyloid neuropathy 0.250 1 1.95e-4 5.35e-4 ✓ sig.
Amyloid neuropathy Partial epilepsy with variable foci 0.250 1 1.95e-4 5.35e-4 ✓ sig.
Amyloid neuropathy Eye manifestations 0.250 1 1.95e-4 5.35e-4 ✓ sig.
Amyloid neuropathy cerebral amyloid angiopathy, app-related 0.250 1 1.95e-4 5.35e-4 ✓ sig.
Acne inversa Early onset alzheimers disease with behavioral disturbance 0.200 1 3.90e-4 8.66e-4 ✓ sig.
Amyloid neuropathy Early onset alzheimers disease with behavioral disturbance 0.200 1 3.90e-4 8.66e-4 ✓ sig.
Acne inversa Amyloid neuropathy 0.167 1 5.84e-4 1.16e-3 ✓ sig.
Acne inversa Dowling degos disease 0.125 1 9.74e-4 1.66e-3 ✓ sig.