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 578
5
Diseases
3
Unique genes
0.357
Avg. similarity score
Autonomic nervous system disease
Most-connected disease (4 links)
Disease
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Autonomic nervous system disease
Bladder dysfunction
Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary cakut
Urinary bladder dysfunction
Hirschsprung disease, cardiac defects, and autonomic dysfunction
Member diseases (most connected first ‐ the cluster's core)
| Disease ⇵ | Connections in cluster ⇵ | Significant partners ⇵ | Curated genes ⇵ |
|---|---|---|---|
| Autonomic nervous system disease | 4 | 4 | 3 |
| Bladder dysfunction | 3 | 3 | 1 |
| Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary cakut | 3 | 3 | 1 |
| Urinary bladder dysfunction | 3 | 3 | 1 |
| Hirschsprung disease, cardiac defects, and autonomic dysfunction | 1 | 1 | 1 |
Top shared genes (genes linked to 2+ member diseases)
| Gene ⇵ | Member diseases ⇵ | Linked diseases |
|---|---|---|
| CHRNA3 | 4 / 5 | Autonomic nervous system disease, Bladder dysfunction, Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary cakut, Urinary bladder dysfunction |
| ECE1 | 2 / 5 | Autonomic nervous system disease, Hirschsprung disease, cardiac defects, and autonomic dysfunction |
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 ⇵ |
|---|---|---|---|---|---|
| Highly sodium permeable postsynaptic acetylcholine nicotinic receptors | Reactome | 1 / 7 | 572× | 1.75e-3 | 1.73e-2 ✓ sig. |
| Nef and signal transduction | Reactome | 1 / 8 | 500× | 2.00e-3 | 1.90e-2 ✓ sig. |
| Highly calcium permeable nicotinic acetylcholine receptors | Reactome | 1 / 9 | 445× | 2.25e-3 | 2.07e-2 ✓ sig. |
| Highly calcium permeable postsynaptic nicotinic acetylcholine receptors | Reactome | 1 / 12 | 334× | 2.99e-3 | 2.54e-2 ✓ sig. |
| PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases | Reactome | 1 / 14 | 286× | 3.49e-3 | 2.83e-2 ✓ sig. |
| FCGR3A-mediated phagocytosis | Reactome | 1 / 59 | 67.9× | 1.47e-2 | 7.17e-2 |
| Regulation of actin dynamics for phagocytic cup formation | Reactome | 1 / 60 | 66.7× | 1.49e-2 | 7.22e-2 |
| VEGFA-VEGFR2 Pathway | Reactome | 1 / 62 | 64.6× | 1.54e-2 | 7.38e-2 |
| Bacterial invasion of epithelial cells | KEGG | 1 / 78 | 51.3× | 1.94e-2 | 8.41e-2 |
| Peptide ligand-binding receptors | Reactome | 1 / 106 | 37.8× | 2.62e-2 | 1.00e-1 |
| Cholinergic synapse | KEGG | 1 / 115 | 34.8× | 2.85e-2 | 1.05e-1 |
| Yersinia infection | KEGG | 1 / 138 | 29.0× | 3.41e-2 | 1.16e-1 |
| Efferocytosis | KEGG | 1 / 157 | 25.5× | 3.87e-2 | 1.25e-1 |
| Chemokine signaling pathway | KEGG | 1 / 193 | 20.7× | 4.74e-2 | 1.41e-1 |
| Chemical carcinogenesis - receptor activation | KEGG | 1 / 215 | 18.6× | 5.28e-2 | 1.49e-1 |
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 acetylcholine secretion, neurotransmission | GO:0014056 | 1 / 1 | 6,229× | 1.61e-4 | 4.34e-3 ✓ sig. |
| calcitonin catabolic process | GO:0010816 | 1 / 1 | 6,229× | 1.61e-4 | 4.34e-3 ✓ sig. |
| endothelin maturation | GO:0034959 | 1 / 1 | 6,229× | 1.61e-4 | 4.34e-3 ✓ sig. |
| substance P catabolic process | GO:0010814 | 1 / 3 | 2,076× | 4.82e-4 | 9.24e-3 ✓ sig. |
| semaphorin-plexin signaling pathway involved in axon guidance | GO:1902287 | 1 / 3 | 2,076× | 4.82e-4 | 9.24e-3 ✓ sig. |
| synaptic transmission involved in micturition | GO:0060084 | 1 / 4 | 1,557× | 6.42e-4 | 1.11e-2 ✓ sig. |
| actin filament-based process | GO:0030029 | 1 / 4 | 1,557× | 6.42e-4 | 1.11e-2 ✓ sig. |
| sympathetic neuron axon guidance | GO:0097492 | 1 / 4 | 1,557× | 6.42e-4 | 1.11e-2 ✓ sig. |
| hormone catabolic process | GO:0042447 | 1 / 5 | 1,246× | 8.03e-4 | 1.28e-2 ✓ sig. |
| regulation of systemic arterial blood pressure by endothelin | GO:0003100 | 1 / 6 | 1,038× | 9.63e-4 | 1.42e-2 ✓ sig. |
| bradykinin catabolic process | GO:0010815 | 1 / 7 | 890× | 1.12e-3 | 1.55e-2 ✓ sig. |
| response to acetylcholine | GO:1905144 | 1 / 8 | 779× | 1.28e-3 | 1.67e-2 ✓ sig. |
| behavioral response to nicotine | GO:0035095 | 1 / 9 | 692× | 1.44e-3 | 1.79e-2 ✓ sig. |
| axonogenesis involved in innervation | GO:0060385 | 1 / 10 | 623× | 1.60e-3 | 1.88e-2 ✓ sig. |
| positive regulation of receptor recycling | GO:0001921 | 1 / 14 | 445× | 2.25e-3 | 2.24e-2 ✓ sig. |
Pairs within this cluster, by significance
| Disease A ⇵ | Disease B ⇵ | Similarity score ⇵ | Shared genes ⇵ | P-value ⇵ | FDR q-value ⇵ |
|---|---|---|---|---|---|
| Bladder dysfunction | Urinary bladder dysfunction | 0.500 | 1 | 6.46e-5 | 1.98e-4 ✓ sig. |
| Bladder dysfunction | Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary cakut | 0.500 | 1 | 6.46e-5 | 1.98e-4 ✓ sig. |
| Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary cakut | Urinary bladder dysfunction | 0.500 | 1 | 6.46e-5 | 1.98e-4 ✓ sig. |
| Autonomic nervous system disease | Hirschsprung disease, cardiac defects, and autonomic dysfunction | 0.250 | 1 | 1.94e-4 | 4.41e-4 ✓ sig. |
| Autonomic nervous system disease | Bladder dysfunction | 0.250 | 1 | 1.94e-4 | 4.41e-4 ✓ sig. |
| Autonomic nervous system disease | Urinary bladder dysfunction | 0.250 | 1 | 1.94e-4 | 4.41e-4 ✓ sig. |
| Autonomic nervous system disease | Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary cakut | 0.250 | 1 | 1.94e-4 | 4.41e-4 ✓ sig. |