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 227
7
Diseases
14
Unique genes
0.145
Avg. similarity score
Iron deficiency anemia
Most-connected disease (5 links)
Disease
Searched: TFRC-related combined immunodeficiency
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TFRC-related combined immunodeficiency
Iron deficiency anemia
Hypochromic microcytic anemia
Hypochromic anemia
Microcytic anemia
Hyperthermia
Hypochromic sideroblastic anemia
Member diseases (most connected first ‐ the cluster's core)
| Disease ⇵ | Connections in cluster ⇵ | Significant partners ⇵ | Curated genes ⇵ |
|---|---|---|---|
| Iron deficiency anemia | 5 | 5 | 10 |
| Hypochromic microcytic anemia | 4 | 4 | 5 |
| Hypochromic anemia | 3 | 3 | 1 |
| Microcytic anemia | 3 | 3 | 4 |
| Hyperthermia | 1 | 1 | 1 |
| Hypochromic sideroblastic anemia | 1 | 1 | 1 |
| TFRC-related combined immunodeficiency | 1 | 1 | 1 |
Top shared genes (genes linked to 2+ member diseases)
| Gene ⇵ | Member diseases ⇵ | Linked diseases |
|---|---|---|
| SLC11A2 | 4 / 7 | Hypochromic anemia, Hypochromic microcytic anemia, Iron deficiency anemia, Microcytic anemia |
| GPX1 | 2 / 7 | Hyperthermia, Iron deficiency anemia |
| STEAP3 | 2 / 7 | Hypochromic microcytic anemia, Hypochromic sideroblastic anemia |
| TF | 2 / 7 | Hypochromic microcytic anemia, Iron deficiency anemia |
| TFRC | 2 / 7 | Iron deficiency anemia, TFRC-related combined immunodeficiency |
| TMPRSS6 | 2 / 7 | Iron deficiency anemia, Microcytic anemia |
| TNF | 2 / 7 | Hypochromic microcytic anemia, Iron deficiency anemia |
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 ⇵ |
|---|---|---|---|---|---|
| Transferrin endocytosis and recycling | Reactome | 4 / 31 | 111× | 3.57e-8 | 2.82e-6 ✓ sig. |
| Ferroptosis | KEGG | 4 / 42 | 81.7× | 1.26e-7 | 8.59e-6 ✓ sig. |
| TGF-beta signaling pathway | KEGG | 4 / 108 | 31.8× | 5.78e-6 | 2.27e-4 ✓ sig. |
| Hematopoietic cell lineage | KEGG | 3 / 100 | 25.7× | 1.91e-4 | 3.87e-3 ✓ sig. |
| Iron uptake and transport | Reactome | 2 / 28 | 61.3× | 4.69e-4 | 7.89e-3 ✓ sig. |
| Detoxification of Reactive Oxygen Species | Reactome | 2 / 34 | 50.5× | 6.93e-4 | 1.06e-2 ✓ sig. |
| Defective SLC11A2 causes hypochromic microcytic anemia, with iron overload 1 (AHMIO1) | Reactome | 1 / 1 | 858× | 1.17e-3 | 1.58e-2 ✓ sig. |
| Mineral absorption | KEGG | 2 / 61 | 28.1× | 2.22e-3 | 2.56e-2 ✓ sig. |
| Longevity regulating pathway - multiple species | KEGG | 2 / 62 | 27.7× | 2.29e-3 | 2.62e-2 ✓ sig. |
| Virion - Rotavirus | KEGG | 1 / 2 | 429× | 2.33e-3 | 2.65e-2 ✓ sig. |
| Hypertrophic cardiomyopathy | KEGG | 2 / 99 | 17.3× | 5.74e-3 | 4.97e-2 ✓ sig. |
| Dilated cardiomyopathy | KEGG | 2 / 105 | 16.3× | 6.43e-3 | 5.36e-2 |
| Cargo recognition for clathrin-mediated endocytosis | Reactome | 2 / 106 | 16.2× | 6.55e-3 | 5.43e-2 |
| TNFR1-mediated ceramide production | Reactome | 1 / 6 | 143× | 6.98e-3 | 5.64e-2 |
| Synthesis of 5-eicosatetraenoic acids | Reactome | 1 / 6 | 143× | 6.98e-3 | 5.64e-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 ⇵ |
|---|---|---|---|---|---|
| intracellular iron ion homeostasis | GO:0006879 | 6 / 71 | 113× | 7.11e-12 | 2.71e-9 ✓ sig. |
| multicellular organismal-level iron ion homeostasis | GO:0060586 | 5 / 28 | 238× | 1.03e-11 | 3.77e-9 ✓ sig. |
| iron ion transport | GO:0006826 | 5 / 31 | 215× | 1.77e-11 | 6.22e-9 ✓ sig. |
| response to iron ion | GO:0010039 | 3 / 18 | 222× | 2.71e-7 | 2.88e-5 ✓ sig. |
| osteoclast differentiation | GO:0030316 | 3 / 49 | 81.7× | 6.04e-6 | 3.62e-4 ✓ sig. |
| response to hypoxia | GO:0001666 | 4 / 176 | 30.3× | 7.07e-6 | 4.09e-4 ✓ sig. |
| cellular response to iron ion | GO:0071281 | 2 / 7 | 381× | 1.09e-5 | 5.79e-4 ✓ sig. |
| response to xenobiotic stimulus | GO:0009410 | 4 / 248 | 21.5× | 2.73e-5 | 1.17e-3 ✓ sig. |
| transferrin transport | GO:0033572 | 2 / 11 | 243× | 2.86e-5 | 1.21e-3 ✓ sig. |
| response to copper ion | GO:0046688 | 2 / 12 | 222× | 3.43e-5 | 1.40e-3 ✓ sig. |
| detection of mechanical stimulus involved in sensory perception of pain | GO:0050966 | 2 / 14 | 191× | 4.72e-5 | 1.78e-3 ✓ sig. |
| cellular response to oxidative stress | GO:0034599 | 3 / 111 | 36.1× | 7.08e-5 | 2.42e-3 ✓ sig. |
| response to reactive oxygen species | GO:0000302 | 2 / 20 | 133× | 9.83e-5 | 3.10e-3 ✓ sig. |
| positive regulation of receptor-mediated endocytosis | GO:0048260 | 2 / 21 | 127× | 1.09e-4 | 3.32e-3 ✓ sig. |
| heart contraction | GO:0060047 | 2 / 23 | 116× | 1.31e-4 | 3.81e-3 ✓ sig. |
Pairs within this cluster, by significance
| Disease A ⇵ | Disease B ⇵ | Similarity score ⇵ | Shared genes ⇵ | P-value ⇵ | FDR q-value ⇵ |
|---|---|---|---|---|---|
| Hypochromic microcytic anemia | Iron deficiency anemia | 0.231 | 3 | 1.97e-9 | 1.73e-8 ✓ sig. |
| Iron deficiency anemia | Microcytic anemia | 0.154 | 2 | 2.28e-6 | 1.26e-5 ✓ sig. |
| Hypochromic anemia | Microcytic anemia | 0.200 | 1 | 2.60e-4 | 6.51e-4 ✓ sig. |
| Hypochromic anemia | Hypochromic microcytic anemia | 0.167 | 1 | 3.25e-4 | 7.71e-4 ✓ sig. |
| Hypochromic microcytic anemia | Hypochromic sideroblastic anemia | 0.167 | 1 | 3.25e-4 | 7.71e-4 ✓ sig. |
| Hyperthermia | Iron deficiency anemia | 0.091 | 1 | 6.49e-4 | 1.24e-3 ✓ sig. |
| Hypochromic anemia | Iron deficiency anemia | 0.091 | 1 | 6.49e-4 | 1.24e-3 ✓ sig. |
| Iron deficiency anemia | TFRC-related combined immunodeficiency | 0.091 | 1 | 6.49e-4 | 1.24e-3 ✓ sig. |
| Hypochromic microcytic anemia | Microcytic anemia | 0.111 | 1 | 1.30e-3 | 2.06e-3 ✓ sig. |