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 159

9 diseases · 18 shared-gene connections
9 Diseases
28 Unique genes
0.190 Avg. similarity score
Thromboangiitis obliterans Most-connected disease (7 links)
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Disease Searched: Anti-glomerular basement membrane disease Pinned (dragged)
Node size = connections within this cluster · edge thickness = similarity strength · hover an edge for its details · click a node to select it and show its pairs below (double-click or Ctrl/⌘-click opens the disease page) · drag a node to pin it in place · scroll/pinch to zoom.

Member diseases (most connected first ‐ the cluster's core)

Disease ⇵ Connections in cluster ⇵ Significant partners ⇵ Curated genes ⇵
Thromboangiitis obliterans 7 7 2
Autoimmune pulmonary alveolar proteinosis 6 6 1
Heerfordt syndrome 6 6 1
Anti-glomerular basement membrane disease 4 4 4
Aortic arch syndrome 4 4 6
Congenital pulmonary artery atresia 3 3 11
Follicular lymphoma 3 3 9
Parapsoriasis 2 2 2
Primary immunodeficiency with defective natural killer cell cytotoxicity 1 1 1

Top shared genes (genes linked to 2+ member diseases)

Gene ⇵ Member diseases ⇵ Linked diseases
HLA-DRB1 7 / 9 Anti-glomerular basement membrane disease, Aortic arch syndrome, Autoimmune pulmonary alveolar proteinosis, Congenital pulmonary artery atresia and 3 more
HLA-A 3 / 9 Aortic arch syndrome, Parapsoriasis, Thromboangiitis obliterans
FCGR3A 2 / 9 Anti-glomerular basement membrane disease, Primary immunodeficiency with defective natural killer cell cytotoxicity
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 ⇵
Autoimmune thyroid disease
CTLA4, HLA-DPB1, HLA-DRB1, HLA-A, HLA-B, IL2, HLA-E
 KEGG 7 / 54 55.6× 2.73e-11 4.17e-9 ✓ sig.
Allograft rejection
HLA-DPB1, HLA-DRB1, HLA-A, HLA-B, IL2, HLA-E
 KEGG 6 / 39 66.0× 2.80e-10 3.40e-8 ✓ sig.
Type I diabetes mellitus
HLA-DPB1, HLA-DRB1, HLA-A, HLA-B, IL2, HLA-E
 KEGG 6 / 44 58.5× 6.02e-10 6.77e-8 ✓ sig.
Graft-versus-host disease
HLA-DPB1, HLA-DRB1, HLA-A, HLA-B, IL2, HLA-E
 KEGG 6 / 45 57.2× 6.93e-10 7.65e-8 ✓ sig.
Viral myocarditis
HLA-DPB1, HLA-DRB1, HLA-A, HLA-B, HLA-E
 KEGG 5 / 70 30.6× 5.15e-7 2.63e-5 ✓ sig.
Human T-cell leukemia virus 1 infection
HLA-DPB1, HLA-DRB1, HLA-A, HLA-B, IL2, CDC27, HLA-E
 KEGG 7 / 224 13.4× 6.06e-7 3.02e-5 ✓ sig.
Endosomal/Vacuolar pathway
HLA-A, HLA-B, HLA-E
 Reactome 3 / 8 161× 6.31e-7 3.13e-5 ✓ sig.
Antigen processing and presentation
HLA-DPB1, HLA-DRB1, HLA-A, HLA-B, HLA-E
 KEGG 5 / 81 26.5× 1.07e-6 4.97e-5 ✓ sig.
Phagosome
FCGR3A, HLA-DPB1, HLA-DRB1, HLA-A, HLA-B, HLA-E
 KEGG 6 / 155 16.6× 1.25e-6 5.69e-5 ✓ sig.
Cell adhesion molecules
CTLA4, HLA-DPB1, HLA-DRB1, HLA-A, HLA-B, HLA-E
 KEGG 6 / 160 16.1× 1.50e-6 6.65e-5 ✓ sig.
Interferon gamma signaling
HLA-DPB1, HLA-DRB1, HLA-A, HLA-B, HLA-E
 Reactome 5 / 87 24.7× 1.53e-6 6.73e-5 ✓ sig.
Herpes simplex virus 1 infection
HLA-DPB1, HLA-DRB1, HLA-A, HLA-B, BCL2, HLA-E
 KEGG 6 / 182 14.1× 3.18e-6 1.26e-4 ✓ sig.
Epstein-Barr virus infection
HLA-DPB1, HLA-DRB1, HLA-A, HLA-B, BCL2, HLA-E
 KEGG 6 / 204 12.6× 6.15e-6 2.16e-4 ✓ sig.
Antigen Presentation: Folding, assembly and peptide loading of class I MHC
HLA-A, HLA-B, HLA-E
 Reactome 3 / 25 51.5× 2.52e-5 7.09e-4 ✓ sig.
Leishmaniasis
FCGR3A, HLA-DPB1, HLA-DRB1, NOS2
 KEGG 4 / 78 22.0× 2.99e-5 8.15e-4 ✓ 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 ⇵
antigen processing and presentation
HLA-DPB1, HLA-DRB1, HLA-A, HLA-B, HLA-E
 GO:0019882 5 / 48 69.5× 8.48e-9 1.46e-6 ✓ sig.
protection from natural killer cell mediated cytotoxicity
HLA-A, HLA-B, HLA-E
 GO:0042270 3 / 6 334× 6.01e-8 7.78e-6 ✓ sig.
positive regulation of T cell mediated cytotoxicity
HLA-DRB1, HLA-A, HLA-B, HLA-E
 GO:0001916 4 / 34 78.5× 1.81e-7 1.99e-5 ✓ sig.
negative regulation of B cell apoptotic process
IL2, BCL2, BCL6
 GO:0002903 3 / 11 182× 4.93e-7 4.61e-5 ✓ sig.
detection of bacterium
HLA-DRB1, HLA-A, HLA-B
 GO:0016045 3 / 12 167× 6.57e-7 5.86e-5 ✓ sig.
immune response
CTLA4, FCGR3A, HLA-DPB1, HLA-DRB1, HLA-A, HLA-B, IL2, HLA-E
 GO:0006955 8 / 543 9.8× 8.98e-7 7.57e-5 ✓ sig.
antigen processing and presentation of endogenous peptide antigen via MHC class Ib
HLA-A, HLA-B, HLA-E
 GO:0002476 3 / 14 143× 1.08e-6 8.89e-5 ✓ sig.
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent
HLA-A, HLA-B, HLA-E
 GO:0002486 3 / 14 143× 1.08e-6 8.89e-5 ✓ sig.
antigen processing and presentation of peptide antigen via MHC class I
HLA-A, HLA-B, HLA-E
 GO:0002474 3 / 17 118× 2.02e-6 1.47e-4 ✓ sig.
positive regulation of CD8-positive, alpha-beta T cell activation
HLA-A, HLA-E
 GO:2001187 2 / 2 667× 2.17e-6 1.54e-4 ✓ sig.
immune system process
CTLA4, FCGR3A, HLA-DPB1, HLA-DRB1, HLA-A, HLA-B, IL2, BCL6, HLA-E
 GO:0002376 9 / 943 6.4× 5.91e-6 3.46e-4 ✓ sig.
positive regulation of CD8-positive, alpha-beta T cell proliferation
HLA-A, HLA-E
 GO:2000566 2 / 3 445× 6.49e-6 3.74e-4 ✓ sig.
adaptive immune response
CTLA4, HLA-DPB1, HLA-DRB1, HLA-A, HLA-B, IL2, HLA-E
 GO:0002250 7 / 507 9.2× 7.49e-6 4.20e-4 ✓ sig.
CD8-positive, alpha-beta T cell activation
HLA-A, HLA-E
 GO:0036037 2 / 4 334× 1.30e-5 6.44e-4 ✓ sig.
T cell receptor signaling pathway
CTLA4, HLA-DPB1, HLA-DRB1, HLA-A
 GO:0050852 4 / 121 22.1× 3.04e-5 1.24e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Aortic arch syndrome Thromboangiitis obliterans 0.286 2 1.27e-7 8.71e-7 ✓ sig.
Autoimmune pulmonary alveolar proteinosis Heerfordt syndrome 0.500 1 6.49e-5 2.33e-4 ✓ sig.
Autoimmune pulmonary alveolar proteinosis Thromboangiitis obliterans 0.333 1 1.30e-4 3.93e-4 ✓ sig.
Heerfordt syndrome Thromboangiitis obliterans 0.333 1 1.30e-4 3.93e-4 ✓ sig.
Parapsoriasis Thromboangiitis obliterans 0.250 1 2.60e-4 6.51e-4 ✓ sig.
Anti-glomerular basement membrane disease Heerfordt syndrome 0.200 1 2.60e-4 6.51e-4 ✓ sig.
Anti-glomerular basement membrane disease Primary immunodeficiency with defective natural killer cell cytotoxicity 0.200 1 2.60e-4 6.51e-4 ✓ sig.
Anti-glomerular basement membrane disease Autoimmune pulmonary alveolar proteinosis 0.200 1 2.60e-4 6.51e-4 ✓ sig.
Aortic arch syndrome Autoimmune pulmonary alveolar proteinosis 0.143 1 3.90e-4 8.66e-4 ✓ sig.
Aortic arch syndrome Heerfordt syndrome 0.143 1 3.90e-4 8.66e-4 ✓ sig.
Anti-glomerular basement membrane disease Thromboangiitis obliterans 0.167 1 5.19e-4 1.06e-3 ✓ sig.
Autoimmune pulmonary alveolar proteinosis Follicular lymphoma 0.100 1 5.84e-4 1.16e-3 ✓ sig.
Follicular lymphoma Heerfordt syndrome 0.100 1 5.84e-4 1.16e-3 ✓ sig.
Autoimmune pulmonary alveolar proteinosis Congenital pulmonary artery atresia 0.083 1 7.14e-4 1.33e-3 ✓ sig.
Congenital pulmonary artery atresia Heerfordt syndrome 0.083 1 7.14e-4 1.33e-3 ✓ sig.
Aortic arch syndrome Parapsoriasis 0.125 1 7.79e-4 1.40e-3 ✓ sig.
Follicular lymphoma Thromboangiitis obliterans 0.091 1 1.17e-3 1.89e-3 ✓ sig.
Congenital pulmonary artery atresia Thromboangiitis obliterans 0.077 1 1.43e-3 2.23e-3 ✓ sig.