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 317
7
Diseases
12
Unique genes
0.236
Avg. similarity score
Adrenal insufficiency
Most-connected disease (4 links)
Disease
Searched: Autoimmunity
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Autoimmunity
Adrenal insufficiency
Lymphopenia
46xy sex reversal 3
Disorder of sex development
Immunodeficiency 126, susceptibility to
Nephrotic syndrome 14
Member diseases (most connected first ‐ the cluster's core)
| Disease ⇵ | Connections in cluster ⇵ | Significant partners ⇵ | Curated genes ⇵ |
|---|---|---|---|
| Adrenal insufficiency | 4 | 4 | 2 |
| Lymphopenia | 4 | 4 | 3 |
| 46xy sex reversal 3 | 2 | 2 | 1 |
| Autoimmunity | 2 | 2 | 8 |
| Disorder of sex development | 2 | 2 | 3 |
| Immunodeficiency 126, susceptibility to | 2 | 2 | 1 |
| Nephrotic syndrome 14 | 2 | 2 | 1 |
Top shared genes (genes linked to 2+ member diseases)
| Gene ⇵ | Member diseases ⇵ | Linked diseases |
|---|---|---|
| NR5A1 | 3 / 7 | 46xy sex reversal 3, Adrenal insufficiency, Disorder of sex development |
| PTCRA | 3 / 7 | Autoimmunity, Immunodeficiency 126, susceptibility to, Lymphopenia |
| SGPL1 | 3 / 7 | Adrenal insufficiency, Lymphopenia, Nephrotic syndrome 14 |
| GIMAP5 | 2 / 7 | Autoimmunity, Lymphopenia |
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 ⇵ |
|---|---|---|---|---|---|
| Relaxin receptors | Reactome | 1 / 8 | 125× | 7.97e-3 | 4.76e-2 ✓ sig. |
| RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) | Reactome | 1 / 10 | 100× | 9.95e-3 | 5.47e-2 |
| Cushing syndrome | KEGG | 2 / 155 | 12.9× | 1.00e-2 | 5.49e-2 |
| Regulation of KIT signaling | Reactome | 1 / 14 | 71.5× | 1.39e-2 | 6.72e-2 |
| Transcriptional misregulation in cancer | KEGG | 2 / 198 | 10.1× | 1.60e-2 | 7.33e-2 |
| Transcriptional regulation of pluripotent stem cells | Reactome | 1 / 17 | 58.9× | 1.69e-2 | 7.56e-2 |
| RHO GTPases activate PKNs | Reactome | 1 / 20 | 50.0× | 1.98e-2 | 8.29e-2 |
| CTLA4 inhibitory signaling | Reactome | 1 / 21 | 47.7× | 2.08e-2 | 8.54e-2 |
| RHO GTPases activate PAKs | Reactome | 1 / 23 | 43.5× | 2.28e-2 | 9.01e-2 |
| SUMOylation of intracellular receptors | Reactome | 1 / 27 | 37.1× | 2.67e-2 | 9.90e-2 |
| Deactivation of the beta-catenin transactivating complex | Reactome | 1 / 42 | 23.8× | 4.12e-2 | 1.28e-1 |
| Sphingolipid de novo biosynthesis | Reactome | 1 / 43 | 23.3× | 4.21e-2 | 1.29e-1 |
| HDMs demethylate histones | Reactome | 1 / 50 | 20.0× | 4.89e-2 | 1.41e-1 |
| Nuclear Receptor transcription pathway | Reactome | 1 / 52 | 19.2× | 5.08e-2 | 1.44e-1 |
| Sphingolipid metabolism | KEGG | 1 / 54 | 18.5× | 5.27e-2 | 1.47e-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 ⇵ |
|---|---|---|---|---|---|
| luteinization | GO:0001553 | 2 / 9 | 346× | 1.36e-5 | 6.72e-4 ✓ sig. |
| Leydig cell differentiation | GO:0033327 | 2 / 11 | 283× | 2.07e-5 | 9.27e-4 ✓ sig. |
| female gonad development | GO:0008585 | 2 / 27 | 115× | 1.32e-4 | 3.70e-3 ✓ sig. |
| hormone-mediated signaling pathway | GO:0009755 | 2 / 42 | 74.2× | 3.21e-4 | 6.91e-3 ✓ sig. |
| primary sex determination | GO:0007538 | 1 / 1 | 1,557× | 6.42e-4 | 1.09e-2 ✓ sig. |
| beta-catenin-TCF complex assembly | GO:1904837 | 1 / 1 | 1,557× | 6.42e-4 | 1.09e-2 ✓ sig. |
| response to gonadotropin-releasing hormone | GO:0097210 | 1 / 2 | 779× | 1.28e-3 | 1.65e-2 ✓ sig. |
| negative regulation of Kit signaling pathway | GO:1900235 | 1 / 2 | 779× | 1.28e-3 | 1.65e-2 ✓ sig. |
| hemopoiesis | GO:0030097 | 2 / 89 | 35.0× | 1.44e-3 | 1.76e-2 ✓ sig. |
| negative regulation of female gonad development | GO:2000195 | 1 / 3 | 519× | 1.93e-3 | 2.04e-2 ✓ sig. |
| monocyte homeostasis | GO:0035702 | 1 / 3 | 519× | 1.93e-3 | 2.04e-2 ✓ sig. |
| intracellular amino acid homeostasis | GO:0080144 | 1 / 3 | 519× | 1.93e-3 | 2.04e-2 ✓ sig. |
| male gonad development | GO:0008584 | 2 / 117 | 26.6× | 2.46e-3 | 2.34e-2 ✓ sig. |
| oocyte growth | GO:0001555 | 1 / 4 | 389× | 2.57e-3 | 2.38e-2 ✓ sig. |
| myeloid cell development | GO:0061515 | 1 / 5 | 311× | 3.21e-3 | 2.66e-2 ✓ sig. |
Pairs within this cluster, by significance
| Disease A ⇵ | Disease B ⇵ | Similarity score ⇵ | Shared genes ⇵ | P-value ⇵ | FDR q-value ⇵ |
|---|---|---|---|---|---|
| Autoimmunity | Lymphopenia | 0.200 | 2 | 7.00e-7 | 4.35e-6 ✓ sig. |
| 46xy sex reversal 3 | Adrenal insufficiency | 0.333 | 1 | 1.29e-4 | 3.27e-4 ✓ sig. |
| Adrenal insufficiency | Nephrotic syndrome 14 | 0.333 | 1 | 1.29e-4 | 3.27e-4 ✓ sig. |
| 46xy sex reversal 3 | Disorder of sex development | 0.250 | 1 | 1.94e-4 | 4.41e-4 ✓ sig. |
| Immunodeficiency 126, susceptibility to | Lymphopenia | 0.250 | 1 | 1.94e-4 | 4.41e-4 ✓ sig. |
| Lymphopenia | Nephrotic syndrome 14 | 0.250 | 1 | 1.94e-4 | 4.41e-4 ✓ sig. |
| Adrenal insufficiency | Disorder of sex development | 0.200 | 1 | 3.87e-4 | 7.33e-4 ✓ sig. |
| Adrenal insufficiency | Lymphopenia | 0.200 | 1 | 3.87e-4 | 7.33e-4 ✓ sig. |
| Autoimmunity | Immunodeficiency 126, susceptibility to | 0.111 | 1 | 5.17e-4 | 9.13e-4 ✓ sig. |