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 187

8 diseases · 24 shared-gene connections
8 Diseases
12 Unique genes
0.375 Avg. similarity score
Annular epidermolytic ichthyosis Most-connected disease (7 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 ⇵
Annular epidermolytic ichthyosis 7 7 2
Congenital reticular ichthyosiform erythroderma 7 7 2
Epidermolytic ichthyosis 7 7 2
Diffuse nonepidermolytic palmoplantar keratoderma 6 6 1
Epidermolytic hyperkeratosis 6 6 2
Keratosis of greither 6 6 1
Epidermolytic palmoplantar keratoderma 5 5 3
Keratosis 4 4 10

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

Gene ⇵ Member diseases ⇵ Linked diseases
KRT1 8 / 8 Annular epidermolytic ichthyosis, Congenital reticular ichthyosiform erythroderma, Diffuse nonepidermolytic palmoplantar keratoderma, Epidermolytic hyperkeratosis and 4 more
KRT10 5 / 8 Annular epidermolytic ichthyosis, Congenital reticular ichthyosiform erythroderma, Epidermolytic hyperkeratosis, Epidermolytic ichthyosis and 1 more
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 ⇵
Chemical carcinogenesis - reactive oxygen species
AHR, CAT, GSTM1, KEAP1, NFE2L2
 KEGG 5 / 227 22.0× 1.64e-6 7.45e-5 ✓ sig.
Formation of the cornified envelope
KRT1, KRT10, KRT16, KRT9
 Reactome 4 / 130 30.8× 6.07e-6 2.21e-4 ✓ sig.
Fluid shear stress and atherosclerosis
GSTM1, KEAP1, NFE2L2, TP53
 KEGG 4 / 141 28.4× 8.38e-6 2.89e-4 ✓ sig.
Keratinization
KRT1, KRT10, KRT16, KRT9
 Reactome 4 / 152 26.3× 1.13e-5 3.71e-4 ✓ sig.
Hepatocellular carcinoma
GSTM1, KEAP1, NFE2L2, TP53
 KEGG 4 / 170 23.5× 1.76e-5 5.37e-4 ✓ sig.
Staphylococcus aureus infection
KRT10, KRT16, KRT9
 KEGG 3 / 99 30.3× 1.13e-4 2.48e-3 ✓ sig.
Estrogen signaling pathway
KRT10, KRT16, KRT9
 KEGG 3 / 139 21.6× 3.09e-4 5.50e-3 ✓ sig.
Pathways in cancer
GSTM1, KEAP1, NFE2L2, TP53
 KEGG 4 / 533 7.5× 1.43e-3 1.78e-2 ✓ sig.
Events associated with phagocytolytic activity of PMN cells
MPO
 Reactome 1 / 2 500× 2.00e-3 2.28e-2 ✓ sig.
Regulation of TP53 Expression
TP53
 Reactome 1 / 2 500× 2.00e-3 2.28e-2 ✓ sig.
Parkinson disease
KEAP1, NFE2L2, TP53
 KEGG 3 / 268 11.2× 2.08e-3 2.35e-2 ✓ sig.
Platinum drug resistance
GSTM1, TP53
 KEGG 2 / 75 26.7× 2.44e-3 2.64e-2 ✓ sig.
Drug metabolism - other enzymes
GSTM1, MPO
 KEGG 2 / 81 24.7× 2.84e-3 2.95e-2 ✓ sig.
Longevity regulating pathway
CAT, TP53
 KEGG 2 / 90 22.2× 3.49e-3 3.42e-2 ✓ sig.
Transcriptional activation of cell cycle inhibitor p21
TP53
 Reactome 1 / 4 250× 3.99e-3 3.77e-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 ⇵
response to oxidative stress
KRT1, CAT, KEAP1, MPO, NFE2L2, TP53
 GO:0006979 6 / 146 64.0× 1.82e-10 4.93e-8 ✓ sig.
intermediate filament organization
KRT1, KRT10, KRT16, KRT9
 GO:0045109 4 / 70 89.0× 8.74e-8 1.08e-5 ✓ sig.
morphogenesis of an epithelium
KRT10, KRT16, KRT9
 GO:0002009 3 / 51 91.6× 4.14e-6 2.58e-4 ✓ sig.
response to xenobiotic stimulus
AHR, CAT, NFE2L2, TP53
 GO:0009410 4 / 248 25.1× 1.38e-5 6.71e-4 ✓ sig.
protein heterotetramerization
KRT1, KRT10
 GO:0051290 2 / 16 195× 4.51e-5 1.67e-3 ✓ sig.
peptide cross-linking
KRT1, KRT10
 GO:0018149 2 / 19 164× 6.43e-5 2.17e-3 ✓ sig.
hydrogen peroxide catabolic process
CAT, MPO
 GO:0042744 2 / 21 148× 7.88e-5 2.53e-3 ✓ sig.
positive regulation of reactive oxygen species metabolic process
NFE2L2, TP53
 GO:2000379 2 / 34 91.6× 2.10e-4 5.21e-3 ✓ sig.
establishment of skin barrier
KRT1, KRT16
 GO:0061436 2 / 37 84.2× 2.49e-4 5.90e-3 ✓ sig.
reactive oxygen species metabolic process
NFE2L2, TP53
 GO:0072593 2 / 45 69.2× 3.69e-4 7.73e-3 ✓ sig.
cellular response to glucose starvation
NFE2L2, TP53
 GO:0042149 2 / 50 62.3× 4.55e-4 8.97e-3 ✓ sig.
response to UV
CAT, TP53
 GO:0009411 2 / 54 57.7× 5.31e-4 9.98e-3 ✓ sig.
response to amitrole
CAT
 GO:0072722 1 / 1 1,557× 6.42e-4 1.13e-2 ✓ sig.
negative regulation of helicase activity
TP53
 GO:0051097 1 / 1 1,557× 6.42e-4 1.13e-2 ✓ sig.
regulation of intrinsic apoptotic signaling pathway by p53 class mediator
TP53
 GO:1902253 1 / 1 1,557× 6.42e-4 1.13e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Annular epidermolytic ichthyosis Congenital reticular ichthyosiform erythroderma 0.667 2 8.44e-9 7.20e-8 ✓ sig.
Epidermolytic hyperkeratosis Epidermolytic ichthyosis 0.667 2 8.44e-9 7.20e-8 ✓ sig.
Congenital reticular ichthyosiform erythroderma Epidermolytic hyperkeratosis 0.667 2 8.44e-9 7.20e-8 ✓ sig.
Congenital reticular ichthyosiform erythroderma Epidermolytic ichthyosis 0.667 2 8.44e-9 7.20e-8 ✓ sig.
Annular epidermolytic ichthyosis Epidermolytic hyperkeratosis 0.667 2 8.44e-9 7.20e-8 ✓ sig.
Annular epidermolytic ichthyosis Epidermolytic ichthyosis 0.667 2 8.44e-9 7.20e-8 ✓ sig.
Epidermolytic hyperkeratosis Keratosis 0.182 2 3.80e-7 2.53e-6 ✓ sig.
Congenital reticular ichthyosiform erythroderma Keratosis 0.182 2 3.80e-7 2.53e-6 ✓ sig.
Epidermolytic ichthyosis Keratosis 0.182 2 3.80e-7 2.53e-6 ✓ sig.
Annular epidermolytic ichthyosis Keratosis 0.182 2 3.80e-7 2.53e-6 ✓ sig.
Diffuse nonepidermolytic palmoplantar keratoderma Keratosis of greither 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Epidermolytic ichthyosis Keratosis of greither 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Annular epidermolytic ichthyosis Keratosis of greither 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Epidermolytic hyperkeratosis Keratosis of greither 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Diffuse nonepidermolytic palmoplantar keratoderma Epidermolytic hyperkeratosis 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Diffuse nonepidermolytic palmoplantar keratoderma Epidermolytic ichthyosis 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Congenital reticular ichthyosiform erythroderma Keratosis of greither 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Congenital reticular ichthyosiform erythroderma Diffuse nonepidermolytic palmoplantar keratoderma 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Annular epidermolytic ichthyosis Diffuse nonepidermolytic palmoplantar keratoderma 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Diffuse nonepidermolytic palmoplantar keratoderma Epidermolytic palmoplantar keratoderma 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Epidermolytic palmoplantar keratoderma Keratosis of greither 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Annular epidermolytic ichthyosis Epidermolytic palmoplantar keratoderma 0.200 1 3.90e-4 8.52e-4 ✓ sig.
Epidermolytic ichthyosis Epidermolytic palmoplantar keratoderma 0.200 1 3.90e-4 8.52e-4 ✓ sig.
Congenital reticular ichthyosiform erythroderma Epidermolytic palmoplantar keratoderma 0.200 1 3.90e-4 8.52e-4 ✓ sig.