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 445
6
Diseases
31
Unique genes
0.208
Avg. similarity score
Multiple system atrophy
Most-connected disease (5 links)
Disease
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Node size = connections within this cluster · edge thickness = similarity strength · hover an edge for its details ·
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Multiple system atrophy
Charcot-Marie-Tooth disease type 2A2
Lipomatosis, multiple symmetric, with or without peripheral neuropathy
Multiple symmetric lipomatosis with partial lipodystrophy
Deafness, autosomal recessive 124
Rib fracture
Member diseases (most connected first ‐ the cluster's core)
| Disease ⇵ | Connections in cluster ⇵ | Significant partners ⇵ | Curated genes ⇵ |
|---|---|---|---|
| Multiple system atrophy | 5 | 5 | 30 |
| Charcot-Marie-Tooth disease type 2A2 | 3 | 3 | 1 |
| Lipomatosis, multiple symmetric, with or without peripheral neuropathy | 3 | 3 | 1 |
| Multiple symmetric lipomatosis with partial lipodystrophy | 3 | 3 | 1 |
| Deafness, autosomal recessive 124 | 1 | 1 | 1 |
| Rib fracture | 1 | 1 | 2 |
Top shared genes (genes linked to 2+ member diseases)
| Gene ⇵ | Member diseases ⇵ | Linked diseases |
|---|---|---|
| MFN2 | 4 / 6 | Charcot-Marie-Tooth disease type 2A2, Lipomatosis, multiple symmetric, with or without peripheral neuropathy, Multiple symmetric lipomatosis with partial lipodystrophy, Multiple system atrophy |
| PKHD1L1 | 2 / 6 | Deafness, autosomal recessive 124, Multiple system atrophy |
| TENM2 | 2 / 6 | Multiple system atrophy, Rib fracture |
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 ⇵ |
|---|---|---|---|---|---|
| Elastic fibre formation | Reactome | 2 / 18 | 43.0× | 9.61e-4 | 1.10e-2 ✓ sig. |
| Activation of RAS in B cells | Reactome | 1 / 5 | 77.5× | 1.28e-2 | 6.60e-2 |
| MET activates PTPN11 | Reactome | 1 / 5 | 77.5× | 1.28e-2 | 6.60e-2 |
| Caffeine metabolism | KEGG | 1 / 6 | 64.6× | 1.54e-2 | 7.38e-2 |
| MET activates PI3K/AKT signaling | Reactome | 1 / 6 | 64.6× | 1.54e-2 | 7.38e-2 |
| Signaling by FGFR3 fusions in cancer | Reactome | 1 / 10 | 38.7× | 2.55e-2 | 9.86e-2 |
| MET receptor recycling | Reactome | 1 / 10 | 38.7× | 2.55e-2 | 9.86e-2 |
| Signaling by FGFR4 in disease | Reactome | 1 / 11 | 35.2× | 2.80e-2 | 1.04e-1 |
| MET activates RAP1 and RAC1 | Reactome | 1 / 11 | 35.2× | 2.80e-2 | 1.04e-1 |
| Mitophagy - animal | KEGG | 2 / 105 | 7.4× | 2.99e-2 | 1.08e-1 |
| Ubiquinone and other terpenoid-quinone biosynthesis | KEGG | 1 / 12 | 32.3× | 3.06e-2 | 1.10e-1 |
| Purine catabolism | Reactome | 1 / 12 | 32.3× | 3.06e-2 | 1.10e-1 |
| Butyrophilin (BTN) family interactions | Reactome | 1 / 12 | 32.3× | 3.06e-2 | 1.10e-1 |
| Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane | Reactome | 1 / 12 | 32.3× | 3.06e-2 | 1.10e-1 |
| Erythropoietin activates Phosphoinositide-3-kinase (PI3K) | Reactome | 1 / 12 | 32.3× | 3.06e-2 | 1.10e-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 ⇵ |
|---|---|---|---|---|---|
| negative regulation of Ras protein signal transduction | GO:0046580 | 2 / 25 | 48.2× | 7.80e-4 | 1.27e-2 ✓ sig. |
| dendritic transport | GO:0098935 | 1 / 1 | 603× | 1.66e-3 | 1.93e-2 ✓ sig. |
| pyrimidine nucleoside transport | GO:0015864 | 1 / 1 | 603× | 1.66e-3 | 1.93e-2 ✓ sig. |
| Spemann organizer formation at the anterior end of the primitive streak | GO:0060064 | 1 / 1 | 603× | 1.66e-3 | 1.93e-2 ✓ sig. |
| hypoxanthine catabolic process | GO:0009114 | 1 / 1 | 603× | 1.66e-3 | 1.93e-2 ✓ sig. |
| xanthine catabolic process | GO:0009115 | 1 / 1 | 603× | 1.66e-3 | 1.93e-2 ✓ sig. |
| visceral mesoderm-endoderm interaction involved in midgut development | GO:0007495 | 1 / 1 | 603× | 1.66e-3 | 1.93e-2 ✓ sig. |
| inosine catabolic process | GO:0006148 | 1 / 2 | 301× | 3.32e-3 | 2.75e-2 ✓ sig. |
| deoxyinosine catabolic process | GO:0006149 | 1 / 2 | 301× | 3.32e-3 | 2.75e-2 ✓ sig. |
| negative regulation of mast cell cytokine production | GO:0032764 | 1 / 2 | 301× | 3.32e-3 | 2.75e-2 ✓ sig. |
| negative regulation of Kit signaling pathway | GO:1900235 | 1 / 2 | 301× | 3.32e-3 | 2.75e-2 ✓ sig. |
| positive regulation of collateral sprouting in absence of injury | GO:0048697 | 1 / 2 | 301× | 3.32e-3 | 2.75e-2 ✓ sig. |
| guanine catabolic process | GO:0006147 | 1 / 2 | 301× | 3.32e-3 | 2.75e-2 ✓ sig. |
| deoxyguanosine catabolic process | GO:0006161 | 1 / 2 | 301× | 3.32e-3 | 2.75e-2 ✓ sig. |
| regulation of neurotransmitter receptor transport, endosome to postsynaptic membrane | GO:0099152 | 1 / 2 | 301× | 3.32e-3 | 2.75e-2 ✓ sig. |
Pairs within this cluster, by significance
| Disease A ⇵ | Disease B ⇵ | Similarity score ⇵ | Shared genes ⇵ | P-value ⇵ | FDR q-value ⇵ |
|---|---|---|---|---|---|
| Charcot-Marie-Tooth disease type 2A2 | Multiple symmetric lipomatosis with partial lipodystrophy | 0.500 | 1 | 6.46e-5 | 1.98e-4 ✓ sig. |
| Charcot-Marie-Tooth disease type 2A2 | Lipomatosis, multiple symmetric, with or without peripheral neuropathy | 0.500 | 1 | 6.46e-5 | 1.98e-4 ✓ sig. |
| Lipomatosis, multiple symmetric, with or without peripheral neuropathy | Multiple symmetric lipomatosis with partial lipodystrophy | 0.500 | 1 | 6.46e-5 | 1.98e-4 ✓ sig. |
| Deafness, autosomal recessive 124 | Multiple system atrophy | 0.032 | 1 | 1.94e-3 | 2.65e-3 ✓ sig. |
| Multiple symmetric lipomatosis with partial lipodystrophy | Multiple system atrophy | 0.032 | 1 | 1.94e-3 | 2.65e-3 ✓ sig. |
| Charcot-Marie-Tooth disease type 2A2 | Multiple system atrophy | 0.032 | 1 | 1.94e-3 | 2.65e-3 ✓ sig. |
| Lipomatosis, multiple symmetric, with or without peripheral neuropathy | Multiple system atrophy | 0.032 | 1 | 1.94e-3 | 2.65e-3 ✓ sig. |
| Multiple system atrophy | Rib fracture | 0.031 | 1 | 3.87e-3 | 4.77e-3 ✓ sig. |