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 318
6
Diseases
35
Unique genes
0.132
Avg. similarity score
Erythropoietic protoporphyria
Most-connected disease (4 links)
Disease
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Erythropoietic protoporphyria
Bile duct disease
Creutzfeldt-jakob disease
protoporphyria, erythropoietic, 1
Bronchopneumonia
SRD5A3-congenital disorder of glycosylation
Member diseases (most connected first ‐ the cluster's core)
| Disease ⇵ | Connections in cluster ⇵ | Significant partners ⇵ | Curated genes ⇵ |
|---|---|---|---|
| Erythropoietic protoporphyria | 4 | 4 | 6 |
| Bile duct disease | 2 | 2 | 2 |
| Creutzfeldt-jakob disease | 2 | 2 | 26 |
| protoporphyria, erythropoietic, 1 | 2 | 2 | 1 |
| Bronchopneumonia | 1 | 1 | 5 |
| SRD5A3-congenital disorder of glycosylation | 1 | 1 | 1 |
Top shared genes (genes linked to 2+ member diseases)
| Gene ⇵ | Member diseases ⇵ | Linked diseases |
|---|---|---|
| FECH | 3 / 6 | Bile duct disease, Erythropoietic protoporphyria, protoporphyria, erythropoietic, 1 |
| AREG | 2 / 6 | Creutzfeldt-jakob disease, Erythropoietic protoporphyria |
| BTC | 2 / 6 | Bronchopneumonia, Erythropoietic protoporphyria |
| EREG | 2 / 6 | Creutzfeldt-jakob disease, Erythropoietic protoporphyria |
| SRD5A3 | 2 / 6 | Creutzfeldt-jakob disease, SRD5A3-congenital disorder of glycosylation |
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 ⇵ |
|---|---|---|---|---|---|
| Inhibition of Signaling by Overexpressed EGFR | Reactome | 3 / 8 | 129× | 1.26e-6 | 5.96e-5 ✓ sig. |
| EGFR interacts with phospholipase C-gamma | Reactome | 3 / 9 | 114× | 1.88e-6 | 8.34e-5 ✓ sig. |
| Signaling by EGFR | Reactome | 3 / 11 | 93.6× | 3.68e-6 | 1.48e-4 ✓ sig. |
| GRB2 events in EGFR signaling | Reactome | 3 / 13 | 79.2× | 6.36e-6 | 2.29e-4 ✓ sig. |
| SHC1 events in EGFR signaling | Reactome | 3 / 14 | 73.5× | 8.07e-6 | 2.80e-4 ✓ sig. |
| GAB1 signalosome | Reactome | 3 / 17 | 60.6× | 1.50e-5 | 4.71e-4 ✓ sig. |
| Estrogen-dependent nuclear events downstream of ESR-membrane signaling | Reactome | 3 / 23 | 44.8× | 3.86e-5 | 1.03e-3 ✓ sig. |
| EGFR downregulation | Reactome | 3 / 31 | 33.2× | 9.64e-5 | 2.18e-3 ✓ sig. |
| ErbB signaling pathway | KEGG | 4 / 86 | 16.0× | 1.08e-4 | 2.40e-3 ✓ sig. |
| PI3K events in ERBB4 signaling | Reactome | 2 / 10 | 68.6× | 3.66e-4 | 6.26e-3 ✓ sig. |
| Signaling by ERBB4 | Reactome | 2 / 11 | 62.4× | 4.46e-4 | 7.29e-3 ✓ sig. |
| Extra-nuclear estrogen signaling | Reactome | 3 / 58 | 17.7× | 6.27e-4 | 9.52e-3 ✓ sig. |
| ERBB2 Activates PTK6 Signaling | Reactome | 2 / 13 | 52.8× | 6.31e-4 | 9.56e-3 ✓ sig. |
| SHC1 events in ERBB4 signaling | Reactome | 2 / 14 | 49.0× | 7.34e-4 | 1.08e-2 ✓ sig. |
| GRB2 events in ERBB2 signaling | Reactome | 2 / 14 | 49.0× | 7.34e-4 | 1.08e-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 ⇵ |
|---|---|---|---|---|---|
| ERBB2-EGFR signaling pathway | GO:0038134 | 3 / 8 | 200× | 3.35e-7 | 3.34e-5 ✓ sig. |
| ERBB4-ERBB4 signaling pathway | GO:0038138 | 2 / 6 | 178× | 5.09e-5 | 1.82e-3 ✓ sig. |
| heme B biosynthetic process | GO:0006785 | 2 / 10 | 107× | 1.52e-4 | 4.14e-3 ✓ sig. |
| epidermal growth factor receptor signaling pathway | GO:0007173 | 3 / 64 | 25.0× | 2.32e-4 | 5.60e-3 ✓ sig. |
| synaptic vesicle docking | GO:0016081 | 2 / 13 | 82.1× | 2.62e-4 | 6.12e-3 ✓ sig. |
| intracellular copper ion homeostasis | GO:0006878 | 2 / 18 | 59.3× | 5.12e-4 | 9.70e-3 ✓ sig. |
| positive regulation of phosphorylation | GO:0042327 | 2 / 20 | 53.4× | 6.34e-4 | 1.13e-2 ✓ sig. |
| vesicle docking | GO:0048278 | 2 / 21 | 50.8× | 7.00e-4 | 1.20e-2 ✓ sig. |
| heme biosynthetic process | GO:0006783 | 2 / 27 | 39.5× | 1.16e-3 | 1.66e-2 ✓ sig. |
| synaptic vesicle exocytosis | GO:0016079 | 2 / 28 | 38.1× | 1.25e-3 | 1.73e-2 ✓ sig. |
| vesicle fusion | GO:0006906 | 2 / 28 | 38.1× | 1.25e-3 | 1.73e-2 ✓ sig. |
| positive regulation of mitotic nuclear division | GO:0045840 | 2 / 29 | 36.8× | 1.34e-3 | 1.80e-2 ✓ sig. |
| negative regulation of T cell receptor signaling pathway | GO:0050860 | 2 / 30 | 35.6× | 1.43e-3 | 1.87e-2 ✓ sig. |
| positive regulation of ATF6-mediated unfolded protein response | GO:1903893 | 1 / 1 | 534× | 1.87e-3 | 2.19e-2 ✓ sig. |
| fructosamine catabolic process | GO:0030392 | 1 / 1 | 534× | 1.87e-3 | 2.19e-2 ✓ sig. |
Pairs within this cluster, by significance
| Disease A ⇵ | Disease B ⇵ | Similarity score ⇵ | Shared genes ⇵ | P-value ⇵ | FDR q-value ⇵ |
|---|---|---|---|---|---|
| Creutzfeldt-jakob disease | Erythropoietic protoporphyria | 0.065 | 2 | 4.10e-5 | 1.98e-4 ✓ sig. |
| Bile duct disease | protoporphyria, erythropoietic, 1 | 0.333 | 1 | 1.30e-4 | 3.90e-4 ✓ sig. |
| Erythropoietic protoporphyria | protoporphyria, erythropoietic, 1 | 0.143 | 1 | 3.90e-4 | 8.52e-4 ✓ sig. |
| Bile duct disease | Erythropoietic protoporphyria | 0.125 | 1 | 7.79e-4 | 1.39e-3 ✓ sig. |
| Creutzfeldt-jakob disease | SRD5A3-congenital disorder of glycosylation | 0.037 | 1 | 1.69e-3 | 2.51e-3 ✓ sig. |
| Bronchopneumonia | Erythropoietic protoporphyria | 0.091 | 1 | 1.95e-3 | 2.81e-3 ✓ sig. |