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 593
5
Diseases
5
Unique genes
0.288
Avg. similarity score
Polymyalgia rheumatica
Most-connected disease (4 links)
Disease
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Polymyalgia rheumatica
Hemochromatosis type 1
Porphyruria
Variegate porphyria
Mannose-binding protein deficiency
Member diseases (most connected first ‐ the cluster's core)
| Disease ⇵ | Connections in cluster ⇵ | Significant partners ⇵ | Curated genes ⇵ |
|---|---|---|---|
| Polymyalgia rheumatica | 4 | 4 | 2 |
| Hemochromatosis type 1 | 3 | 3 | 1 |
| Porphyruria | 3 | 3 | 2 |
| Variegate porphyria | 3 | 3 | 4 |
| Mannose-binding protein deficiency | 1 | 1 | 1 |
Top shared genes (genes linked to 2+ member diseases)
| Gene ⇵ | Member diseases ⇵ | Linked diseases |
|---|---|---|
| HFE | 4 / 5 | Hemochromatosis type 1, Polymyalgia rheumatica, Porphyruria, Variegate porphyria |
| MBL2 | 2 / 5 | Mannose-binding protein deficiency, Polymyalgia rheumatica |
| PPOX | 2 / 5 | Porphyruria, Variegate porphyria |
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 ⇵ |
|---|---|---|---|---|---|
| Lectin pathway of complement activation | Reactome | 1 / 8 | 300× | 3.33e-3 | 2.74e-2 ✓ sig. |
| TNFR1-induced proapoptotic signaling | Reactome | 1 / 13 | 185× | 5.40e-3 | 3.84e-2 ✓ sig. |
| Glycosaminoglycan biosynthesis - keratan sulfate | KEGG | 1 / 14 | 172× | 5.82e-3 | 4.03e-2 ✓ sig. |
| Heme biosynthesis | Reactome | 1 / 14 | 172× | 5.82e-3 | 4.03e-2 ✓ sig. |
| N-Glycan antennae elongation | Reactome | 1 / 15 | 160× | 6.23e-3 | 4.21e-2 ✓ sig. |
| Initial triggering of complement | Reactome | 1 / 17 | 141× | 7.06e-3 | 4.56e-2 ✓ sig. |
| Mannose type O-glycan biosynthesis | KEGG | 1 / 23 | 104× | 9.54e-3 | 5.53e-2 |
| Glycosphingolipid biosynthesis - lacto and neolacto series | KEGG | 1 / 28 | 85.8× | 1.16e-2 | 6.22e-2 |
| Keratan sulfate biosynthesis | Reactome | 1 / 28 | 85.8× | 1.16e-2 | 6.22e-2 |
| TNFR1-induced NFkappaB signaling pathway | Reactome | 1 / 30 | 80.1× | 1.24e-2 | 6.49e-2 |
| Transferrin endocytosis and recycling | Reactome | 1 / 31 | 77.5× | 1.28e-2 | 6.60e-2 |
| Regulation of TNFR1 signaling | Reactome | 1 / 33 | 72.8× | 1.37e-2 | 6.87e-2 |
| Various types of N-glycan biosynthesis | KEGG | 1 / 43 | 55.9× | 1.78e-2 | 8.02e-2 |
| Porphyrin metabolism | KEGG | 1 / 46 | 52.2× | 1.90e-2 | 8.32e-2 |
| Other types of O-glycan biosynthesis | KEGG | 1 / 47 | 51.1× | 1.94e-2 | 8.43e-2 |
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 antigen processing and presentation of endogenous peptide antigen via MHC class I | GO:1904283 | 1 / 1 | 3,737× | 2.68e-4 | 6.25e-3 ✓ sig. |
| regulation of iron ion transport | GO:0034756 | 1 / 2 | 1,869× | 5.35e-4 | 9.88e-3 ✓ sig. |
| regulation of T cell mediated immunity | GO:0002709 | 1 / 2 | 1,869× | 5.35e-4 | 9.88e-3 ✓ sig. |
| protoporphyrinogen IX metabolic process | GO:0046501 | 1 / 3 | 1,246× | 8.03e-4 | 1.28e-2 ✓ sig. |
| response to iron ion starvation | GO:1990641 | 1 / 3 | 1,246× | 8.03e-4 | 1.28e-2 ✓ sig. |
| negative regulation of CD8-positive, alpha-beta T cell activation | GO:2001186 | 1 / 4 | 934× | 1.07e-3 | 1.51e-2 ✓ sig. |
| negative regulation of viral process | GO:0048525 | 1 / 5 | 747× | 1.34e-3 | 1.71e-2 ✓ sig. |
| galactosylceramide biosynthetic process | GO:0006682 | 1 / 6 | 623× | 1.60e-3 | 1.88e-2 ✓ sig. |
| cellular response to iron ion | GO:0071281 | 1 / 7 | 534× | 1.87e-3 | 2.05e-2 ✓ sig. |
| negative regulation of T cell cytokine production | GO:0002725 | 1 / 7 | 534× | 1.87e-3 | 2.05e-2 ✓ sig. |
| positive regulation of opsonization | GO:1903028 | 1 / 9 | 415× | 2.41e-3 | 2.32e-2 ✓ sig. |
| protoporphyrinogen IX biosynthetic process | GO:0006782 | 1 / 9 | 415× | 2.41e-3 | 2.32e-2 ✓ sig. |
| heme O biosynthetic process | GO:0048034 | 1 / 9 | 415× | 2.41e-3 | 2.32e-2 ✓ sig. |
| positive regulation of peptide hormone secretion | GO:0090277 | 1 / 10 | 374× | 2.67e-3 | 2.46e-2 ✓ sig. |
| heme A biosynthetic process | GO:0006784 | 1 / 10 | 374× | 2.67e-3 | 2.46e-2 ✓ sig. |
Pairs within this cluster, by significance
| Disease A ⇵ | Disease B ⇵ | Similarity score ⇵ | Shared genes ⇵ | P-value ⇵ | FDR q-value ⇵ |
|---|---|---|---|---|---|
| Porphyruria | Variegate porphyria | 0.400 | 2 | 5.00e-8 | 3.63e-7 ✓ sig. |
| Hemochromatosis type 1 | Polymyalgia rheumatica | 0.333 | 1 | 1.29e-4 | 3.27e-4 ✓ sig. |
| Hemochromatosis type 1 | Porphyruria | 0.333 | 1 | 1.29e-4 | 3.27e-4 ✓ sig. |
| Mannose-binding protein deficiency | Polymyalgia rheumatica | 0.333 | 1 | 1.29e-4 | 3.27e-4 ✓ sig. |
| Polymyalgia rheumatica | Porphyruria | 0.250 | 1 | 2.58e-4 | 5.38e-4 ✓ sig. |
| Hemochromatosis type 1 | Variegate porphyria | 0.200 | 1 | 2.58e-4 | 5.38e-4 ✓ sig. |
| Polymyalgia rheumatica | Variegate porphyria | 0.167 | 1 | 5.16e-4 | 9.13e-4 ✓ sig. |