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 551

5 diseases · 7 shared-gene connections
5 Diseases
11 Unique genes
0.219 Avg. similarity score
Lupus Most-connected disease (4 links)
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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 ⇵
Lupus 4 4 3
C2 deficiency 3 3 1
Immunodeficiency due to c1, c4, or c2 component complement deficiency 3 3 1
Irritant dermatitis 3 3 9
Immunodeficiency, common variable, 7 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
C2 4 / 5 C2 deficiency, Immunodeficiency due to c1, c4, or c2 component complement deficiency, Irritant dermatitis, Lupus
CR2 2 / 5 Immunodeficiency, common variable, 7, Lupus
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 ⇵
Interferon gamma signaling
HLA-DPA1, HLA-DPB1, TRIM10, TRIM31
 Reactome 4 / 87 50.2× 8.15e-7 3.48e-5 ✓ sig.
Staphylococcus aureus infection
C2, HLA-DPA1, HLA-DPB1
 KEGG 3 / 99 33.1× 8.55e-5 1.68e-3 ✓ sig.
Hematopoietic cell lineage
HLA-DPA1, HLA-DPB1, CR2
 KEGG 3 / 100 32.8× 8.81e-5 1.72e-3 ✓ sig.
Translocation of ZAP-70 to Immunological synapse
HLA-DPA1, HLA-DPB1
 Reactome 2 / 19 115× 1.29e-4 2.32e-3 ✓ sig.
Phosphorylation of CD3 and TCR zeta chains
HLA-DPA1, HLA-DPB1
 Reactome 2 / 22 99.3× 1.74e-4 2.95e-3 ✓ sig.
PD-1 signaling
HLA-DPA1, HLA-DPB1
 Reactome 2 / 23 94.9× 1.91e-4 3.16e-3 ✓ sig.
Systemic lupus erythematosus
C2, HLA-DPA1, HLA-DPB1
 KEGG 3 / 140 23.4× 2.39e-4 3.77e-3 ✓ sig.
Generation of second messenger molecules
HLA-DPA1, HLA-DPB1
 Reactome 2 / 31 70.4× 3.50e-4 5.06e-3 ✓ sig.
Asthma
HLA-DPA1, HLA-DPB1
 KEGG 2 / 32 68.2× 3.73e-4 5.32e-3 ✓ sig.
Allograft rejection
HLA-DPA1, HLA-DPB1
 KEGG 2 / 39 56.0× 5.55e-4 7.25e-3 ✓ sig.
Type I diabetes mellitus
HLA-DPA1, HLA-DPB1
 KEGG 2 / 44 49.6× 7.07e-4 8.71e-3 ✓ sig.
Epstein-Barr virus infection
HLA-DPA1, HLA-DPB1, CR2
 KEGG 3 / 204 16.1× 7.21e-4 8.84e-3 ✓ sig.
Graft-versus-host disease
HLA-DPA1, HLA-DPB1
 KEGG 2 / 45 48.5× 7.39e-4 9.01e-3 ✓ sig.
Regulation of Complement cascade
C2, CR2
 Reactome 2 / 47 46.5× 8.06e-4 9.61e-3 ✓ sig.
Intestinal immune network for IgA production
HLA-DPA1, HLA-DPB1
 KEGG 2 / 50 43.7× 9.12e-4 1.06e-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 ⇵
innate immune response
C2, TRIM10, TRIM31, TRIM40, CR2
 GO:0045087 5 / 605 14.0× 1.37e-5 6.97e-4 ✓ sig.
antigen processing and presentation of peptide or polysaccharide antigen via MHC class II
HLA-DPA1, HLA-DPB1
 GO:0002504 2 / 15 227× 3.29e-5 1.35e-3 ✓ sig.
peptide antigen assembly with MHC class II protein complex
HLA-DPA1, HLA-DPB1
 GO:0002503 2 / 16 212× 3.76e-5 1.49e-3 ✓ sig.
host-mediated suppression of symbiont invasion
TRIM10, TRIM31
 GO:0046597 2 / 24 142× 8.63e-5 2.77e-3 ✓ sig.
immune system process
C2, HLA-DPA1, HLA-DPB1, TRIM31, CR2
 GO:0002376 5 / 943 9.0× 1.16e-4 3.44e-3 ✓ sig.
antigen processing and presentation of exogenous peptide antigen via MHC class II
HLA-DPA1, HLA-DPB1
 GO:0019886 2 / 31 110× 1.45e-4 4.04e-3 ✓ sig.
complement activation, classical pathway
C2, CR2
 GO:0006958 2 / 37 91.8× 2.07e-4 5.22e-3 ✓ sig.
positive regulation of immune response
HLA-DPA1, HLA-DPB1
 GO:0050778 2 / 40 84.9× 2.43e-4 5.82e-3 ✓ sig.
positive regulation of T cell activation
HLA-DPA1, HLA-DPB1
 GO:0050870 2 / 45 75.5× 3.08e-4 6.90e-3 ✓ sig.
antigen processing and presentation
HLA-DPA1, HLA-DPB1
 GO:0019882 2 / 48 70.8× 3.50e-4 7.49e-3 ✓ sig.
negative regulation of interleukin-2-mediated signaling pathway
PTPN2
 GO:1902206 1 / 1 1,699× 5.89e-4 1.06e-2 ✓ sig.
negative regulation of positive thymic T cell selection
PTPN2
 GO:1902233 1 / 1 1,699× 5.89e-4 1.06e-2 ✓ sig.
erythrocyte differentiation
TRIM10, PTPN2
 GO:0030218 2 / 65 52.3× 6.42e-4 1.11e-2 ✓ sig.
positive regulation of T cell proliferation
HLA-DPA1, HLA-DPB1
 GO:0042102 2 / 67 50.7× 6.82e-4 1.17e-2 ✓ sig.
positive regulation of type II interferon production
HLA-DPA1, HLA-DPB1
 GO:0032729 2 / 77 44.1× 9.00e-4 1.38e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
C2 deficiency Immunodeficiency due to c1, c4, or c2 component complement deficiency 0.500 1 6.46e-5 1.98e-4 ✓ sig.
C2 deficiency Lupus 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Immunodeficiency due to c1, c4, or c2 component complement deficiency Lupus 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Immunodeficiency, common variable, 7 Lupus 0.250 1 1.94e-4 4.41e-4 ✓ sig.
C2 deficiency Irritant dermatitis 0.100 1 5.81e-4 1.00e-3 ✓ sig.
Immunodeficiency due to c1, c4, or c2 component complement deficiency Irritant dermatitis 0.100 1 5.81e-4 1.00e-3 ✓ sig.
Irritant dermatitis Lupus 0.083 1 1.74e-3 2.42e-3 ✓ sig.