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 434
5
Diseases
7
Unique genes
0.186
Avg. similarity score
Pelizaeus-merzbacher disease
Most-connected disease (4 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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Pelizaeus-merzbacher disease
Pelizaeus-Merzbacher spectrum disorder
Spastic paraplegia, x-linked
hypomyelinating leukodystrophy 2
hypomyelinating leukodystrophy 3
Member diseases (most connected first ‐ the cluster's core)
| Disease ⇵ | Connections in cluster ⇵ | Significant partners ⇵ | Curated genes ⇵ |
|---|---|---|---|
| Pelizaeus-merzbacher disease | 4 | 4 | 6 |
| Pelizaeus-Merzbacher spectrum disorder | 2 | 2 | 1 |
| Spastic paraplegia, x-linked | 2 | 2 | 3 |
| hypomyelinating leukodystrophy 2 | 1 | 1 | 1 |
| hypomyelinating leukodystrophy 3 | 1 | 1 | 1 |
Top shared genes (genes linked to 2+ member diseases)
| Gene ⇵ | Member diseases ⇵ | Linked diseases |
|---|---|---|
| PLP1 | 3 / 5 | Pelizaeus-merzbacher disease, Pelizaeus-Merzbacher spectrum disorder, Spastic paraplegia, x-linked |
| AIMP1 | 2 / 5 | hypomyelinating leukodystrophy 3, Pelizaeus-merzbacher disease |
| GJC2 | 2 / 5 | hypomyelinating leukodystrophy 2, Pelizaeus-merzbacher disease |
| RAB9B | 2 / 5 | Pelizaeus-merzbacher disease, Spastic paraplegia, x-linked |
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 ⇵ |
|---|---|---|---|---|---|
| TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation | Reactome | 1 / 5 | 343× | 2.91e-3 | 3.01e-2 ✓ sig. |
| Gap junction assembly | Reactome | 1 / 18 | 95.3× | 1.04e-2 | 7.05e-2 |
| Mitochondrial protein import | Reactome | 1 / 19 | 90.3× | 1.10e-2 | 7.27e-2 |
| Cytosolic tRNA aminoacylation | Reactome | 1 / 24 | 71.5× | 1.39e-2 | 8.31e-2 |
| Sealing of the nuclear envelope (NE) by ESCRT-III | Reactome | 1 / 31 | 55.3× | 1.79e-2 | 9.70e-2 |
| Type I diabetes mellitus | KEGG | 1 / 44 | 39.0× | 2.54e-2 | 1.17e-1 |
| Retrograde transport at the Trans-Golgi-Network | Reactome | 1 / 46 | 37.3× | 2.65e-2 | 1.20e-1 |
| Legionellosis | KEGG | 1 / 56 | 30.6× | 3.22e-2 | 1.34e-1 |
| RAB geranylgeranylation | Reactome | 1 / 65 | 26.4× | 3.73e-2 | 1.46e-1 |
| RNA degradation | KEGG | 1 / 78 | 22.0× | 4.46e-2 | 1.61e-1 |
| RAB GEFs exchange GTP for GDP on RABs | Reactome | 1 / 90 | 19.1× | 5.13e-2 | 1.74e-1 |
| Measles | KEGG | 1 / 139 | 12.3× | 7.83e-2 | 2.17e-1 |
| Tuberculosis | KEGG | 1 / 181 | 9.5× | 1.01e-1 | 2.49e-1 |
| Lipid and atherosclerosis | KEGG | 1 / 216 | 7.9× | 1.19e-1 | 2.72e-1 |
| Salmonella infection | KEGG | 1 / 248 | 6.9× | 1.36e-1 | 2.93e-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 ⇵ |
|---|---|---|---|---|---|
| central nervous system myelination | GO:0022010 | 2 / 16 | 334× | 1.44e-5 | 6.94e-4 ✓ sig. |
| myelination | GO:0042552 | 2 / 73 | 73.1× | 3.12e-4 | 6.92e-3 ✓ sig. |
| isotype switching to IgG isotypes | GO:0048291 | 1 / 1 | 2,670× | 3.75e-4 | 7.81e-3 ✓ sig. |
| protein insertion into plasma membrane | GO:0098737 | 1 / 1 | 2,670× | 3.75e-4 | 7.81e-3 ✓ sig. |
| positive regulation of glucagon secretion | GO:0070094 | 1 / 2 | 1,335× | 7.49e-4 | 1.25e-2 ✓ sig. |
| mitochondrial unfolded protein response | GO:0034514 | 1 / 2 | 1,335× | 7.49e-4 | 1.25e-2 ✓ sig. |
| mitotic spindle disassembly | GO:0051228 | 1 / 3 | 890× | 1.12e-3 | 1.62e-2 ✓ sig. |
| cytokinetic process | GO:0032506 | 1 / 3 | 890× | 1.12e-3 | 1.62e-2 ✓ sig. |
| membrane raft polarization | GO:0001766 | 1 / 3 | 890× | 1.12e-3 | 1.62e-2 ✓ sig. |
| 'de novo' protein folding | GO:0006458 | 1 / 3 | 890× | 1.12e-3 | 1.62e-2 ✓ sig. |
| protein import into mitochondrial intermembrane space | GO:0045041 | 1 / 3 | 890× | 1.12e-3 | 1.62e-2 ✓ sig. |
| adhesion of symbiont to host | GO:0044406 | 1 / 4 | 667× | 1.50e-3 | 1.91e-2 ✓ sig. |
| protein localization to paranode region of axon | GO:0002175 | 1 / 4 | 667× | 1.50e-3 | 1.91e-2 ✓ sig. |
| positive regulation of microtubule depolymerization | GO:0031117 | 1 / 5 | 534× | 1.87e-3 | 2.19e-2 ✓ sig. |
| biological process involved in interaction with symbiont | GO:0051702 | 1 / 6 | 445× | 2.25e-3 | 2.41e-2 ✓ sig. |
Pairs within this cluster, by significance
| Disease A ⇵ | Disease B ⇵ | Similarity score ⇵ | Shared genes ⇵ | P-value ⇵ | FDR q-value ⇵ |
|---|---|---|---|---|---|
| Pelizaeus-merzbacher disease | Spastic paraplegia, x-linked | 0.250 | 2 | 3.80e-7 | 2.53e-6 ✓ sig. |
| Pelizaeus-Merzbacher spectrum disorder | Spastic paraplegia, x-linked | 0.250 | 1 | 1.95e-4 | 5.28e-4 ✓ sig. |
| hypomyelinating leukodystrophy 2 | Pelizaeus-merzbacher disease | 0.143 | 1 | 3.90e-4 | 8.52e-4 ✓ sig. |
| hypomyelinating leukodystrophy 3 | Pelizaeus-merzbacher disease | 0.143 | 1 | 3.90e-4 | 8.52e-4 ✓ sig. |
| Pelizaeus-merzbacher disease | Pelizaeus-Merzbacher spectrum disorder | 0.143 | 1 | 3.90e-4 | 8.52e-4 ✓ sig. |