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 101

12 diseases · 20 shared-gene connections
12 Diseases
26 Unique genes
0.202 Avg. similarity score
Eye pain 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 ⇵
Eye pain 7 7 1
Immune system disorder 6 6 5
Rhabdomyoma 6 6 1
Sacroiliitis 5 5 1
Constipation 4 4 5
Facial nerve disorder 4 4 8
Hypocalcemia 2 2 6
Nausea 2 2 7
Anterior cruciate ligament injury 1 1 1
Arginase deficiency 1 1 1
Congenital hereditary facial paralysis with variable hearing loss syndrome 1 1 1
pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
POMC 8 / 12 Constipation, Eye pain, Facial nerve disorder, Hypocalcemia and 4 more
ARG1 2 / 12 Arginase deficiency, Immune system disorder
CNR2 2 / 12 Anterior cruciate ligament injury, Immune system disorder
EIF2AK4 2 / 12 Immune system disorder, pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis
HOXB1 2 / 12 Congenital hereditary facial paralysis with variable hearing loss syndrome, Facial nerve disorder
OPRM1 2 / 12 Constipation, Nausea
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 ⇵
Amoebiasis
ARG1, GNA11, GNAS, IFNG, TNF
 KEGG 5 / 103 22.4× 2.40e-6 1.03e-4 ✓ sig.
Hormone signaling
GNA11, GCG, OPRM1, POMC, GNAS, PTH
 KEGG 6 / 219 12.7× 5.83e-6 2.15e-4 ✓ sig.
ADORA2B mediated anti-inflammatory cytokines production
GCG, GPBAR1, POMC, GNAS, PTH
 Reactome 5 / 128 18.0× 6.99e-6 2.49e-4 ✓ sig.
G alpha (s) signalling events
GCG, GPBAR1, POMC, GNAS, PTH
 Reactome 5 / 140 16.5× 1.08e-5 3.59e-4 ✓ sig.
Opioid Signalling
OPRM1, POMC
 Reactome 2 / 3 308× 1.35e-5 4.31e-4 ✓ sig.
Necroptosis
TRPM7, IFNA2, IFNG, TNF, TNFRSF10A
 KEGG 5 / 159 14.5× 2.01e-5 5.99e-4 ✓ sig.
Aldosterone synthesis and secretion
GNA11, POMC, ATP2B1, GNAS
 KEGG 4 / 98 18.9× 5.43e-5 1.37e-3 ✓ sig.
Chagas disease
GNA11, GNAS, IFNG, TNF
 KEGG 4 / 103 17.9× 6.60e-5 1.60e-3 ✓ sig.
Parathyroid hormone synthesis, secretion and action
CASR, GNA11, GNAS, PTH
 KEGG 4 / 115 16.1× 1.01e-4 2.28e-3 ✓ sig.
Natural killer cell mediated cytotoxicity
IFNA2, IFNG, TNF, TNFRSF10A
 KEGG 4 / 133 13.9× 1.78e-4 3.57e-3 ✓ sig.
Endocrine and other factor-regulated calcium reabsorption
ATP2B1, GNAS, PTH
 KEGG 3 / 53 26.1× 1.96e-4 3.85e-3 ✓ sig.
Hepatitis C
EIF2AK4, IFNA2, IFNG, TNF
 KEGG 4 / 159 11.6× 3.52e-4 6.09e-3 ✓ sig.
Cortisol synthesis and secretion
GNA11, POMC, GNAS
 KEGG 3 / 65 21.3× 3.60e-4 6.18e-3 ✓ sig.
Influenza A
IFNA2, IFNG, TNF, TNFRSF10A
 KEGG 4 / 173 10.7× 4.85e-4 7.79e-3 ✓ sig.
Herpes simplex virus 1 infection
EIF2AK4, IFNA2, IFNG, TNF
 KEGG 4 / 182 10.2× 5.88e-4 9.03e-3 ✓ 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 ⇵
regulation of insulin secretion
GCG, GNAS, IFNG, TNF
 GO:0050796 4 / 46 62.5× 4.62e-7 4.37e-5 ✓ sig.
positive regulation of neutrophil mediated killing of fungus
ARG1, POMC
 GO:0070965 2 / 2 719× 1.86e-6 1.36e-4 ✓ sig.
positive regulation of vitamin D biosynthetic process
IFNG, TNF
 GO:0060557 2 / 2 719× 1.86e-6 1.36e-4 ✓ sig.
adenylate cyclase-activating G protein-coupled receptor signaling pathway
CNR2, CASR, GCG, GNAS, PTH
 GO:0007189 5 / 161 22.3× 2.53e-6 1.74e-4 ✓ sig.
positive regulation of ERK1 and ERK2 cascade
CASR, GCG, GPBAR1, OPRM1, TNF
 GO:0070374 5 / 201 17.9× 7.50e-6 4.15e-4 ✓ sig.
negative regulation of T-helper 2 cell cytokine production
ARG1, IFNA2
 GO:2000552 2 / 4 359× 1.11e-5 5.66e-4 ✓ sig.
adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway
CASR, PTH
 GO:0140582 2 / 5 287× 1.86e-5 8.45e-4 ✓ sig.
response to parathyroid hormone
GNAS, PTH
 GO:0071107 2 / 5 287× 1.86e-5 8.45e-4 ✓ sig.
magnesium ion homeostasis
TRPM7, PTH
 GO:0010960 2 / 8 180× 5.19e-5 1.85e-3 ✓ sig.
G protein-coupled receptor signaling pathway
CNR2, CASR, GNA11, GCG, GPBAR1, OPRM1, GNAS, PTH
 GO:0007186 8 / 1,031 5.6× 5.35e-5 1.89e-3 ✓ sig.
extrinsic apoptotic signaling pathway
IFNG, TNF, TNFRSF10A
 GO:0097191 3 / 57 37.8× 6.66e-5 2.23e-3 ✓ sig.
humoral immune response
IFNA2, IFNG, TNF
 GO:0006959 3 / 58 37.2× 7.01e-5 2.32e-3 ✓ sig.
cellular response to glucagon stimulus
GCG, GNAS
 GO:0071377 2 / 11 131× 1.02e-4 3.06e-3 ✓ sig.
negative regulation of cytosolic calcium ion concentration
OPRM1, ATP2B1
 GO:0051481 2 / 11 131× 1.02e-4 3.06e-3 ✓ sig.
response to fibroblast growth factor
CASR, PTH
 GO:0071774 2 / 11 131× 1.02e-4 3.06e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Constipation Nausea 0.182 2 1.77e-6 1.05e-5 ✓ sig.
Rhabdomyoma Sacroiliitis 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Eye pain Rhabdomyoma 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Eye pain Sacroiliitis 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Arginase deficiency Immune system disorder 0.167 1 3.25e-4 7.58e-4 ✓ sig.
Immune system disorder Sacroiliitis 0.167 1 3.25e-4 7.58e-4 ✓ sig.
Immune system disorder Rhabdomyoma 0.167 1 3.25e-4 7.58e-4 ✓ sig.
Eye pain Immune system disorder 0.167 1 3.25e-4 7.58e-4 ✓ sig.
Immune system disorder pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis 0.167 1 3.25e-4 7.58e-4 ✓ sig.
Constipation Sacroiliitis 0.167 1 3.25e-4 7.58e-4 ✓ sig.
Constipation Rhabdomyoma 0.167 1 3.25e-4 7.58e-4 ✓ sig.
Constipation Eye pain 0.167 1 3.25e-4 7.58e-4 ✓ sig.
Anterior cruciate ligament injury Immune system disorder 0.167 1 3.25e-4 7.58e-4 ✓ sig.
Eye pain Hypocalcemia 0.143 1 3.90e-4 8.52e-4 ✓ sig.
Hypocalcemia Rhabdomyoma 0.143 1 3.90e-4 8.52e-4 ✓ sig.
Eye pain Nausea 0.125 1 4.55e-4 9.55e-4 ✓ sig.
Eye pain Facial nerve disorder 0.111 1 5.20e-4 1.04e-3 ✓ sig.
Facial nerve disorder Rhabdomyoma 0.111 1 5.20e-4 1.04e-3 ✓ sig.
Facial nerve disorder Sacroiliitis 0.111 1 5.20e-4 1.04e-3 ✓ sig.
Congenital hereditary facial paralysis with variable hearing loss syndrome Facial nerve disorder 0.111 1 5.20e-4 1.04e-3 ✓ sig.