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 292

8 diseases · 14 shared-gene connections
8 Diseases
8 Unique genes
0.227 Avg. similarity score
Complement pathway abnormality Most-connected disease (7 links)
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Disease Searched: Systemic lupus erythematosus related to C1QA 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 ⇵
Complement pathway abnormality 7 7 8
Immunodeficiency due to a classical component pathway complement deficiency 5 5 4
C1q deficiency 4 4 3
Periodontal ehlers-danlos syndrome 3 3 2
Systemic lupus erythematosus related to C1QA 3 3 1
C1s deficiency 2 2 1
C4a deficiency 2 2 1
Immunodeficiency due to an early component of complement deficiency 2 2 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
C1QA 4 / 8 C1q deficiency, Complement pathway abnormality, Immunodeficiency due to a classical component pathway complement deficiency, Systemic lupus erythematosus related to C1QA
C1QB 3 / 8 C1q deficiency, Complement pathway abnormality, Immunodeficiency due to an early component of complement deficiency
C1QC 3 / 8 C1q deficiency, Complement pathway abnormality, Immunodeficiency due to a classical component pathway complement deficiency
C1R 3 / 8 Complement pathway abnormality, Immunodeficiency due to a classical component pathway complement deficiency, Periodontal ehlers-danlos syndrome
C1S 3 / 8 C1s deficiency, Complement pathway abnormality, Periodontal ehlers-danlos syndrome
C4A 3 / 8 C4a deficiency, Complement pathway abnormality, Immunodeficiency due to a classical component pathway complement deficiency
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 ⇵
Initial triggering of complement
C1QA, C1QB, C1QC, C1R, C1S, C2, C4A, C4B
 Reactome 8 / 17 706× 2.27e-24 3.34e-21 ✓ sig.
Regulation of Complement cascade
C1QA, C1QB, C1QC, C1R, C1S, C2, C4A, C4B
 Reactome 8 / 47 256× 2.94e-20 2.24e-17 ✓ sig.
Pertussis
C1QA, C1QB, C1QC, C1R, C1S, C2, C4A, C4B
 KEGG 8 / 78 154× 2.19e-18 1.27e-15 ✓ sig.
Complement and coagulation cascades
C1QA, C1QB, C1QC, C1R, C1S, C2, C4A, C4B
 KEGG 8 / 88 136× 6.00e-18 3.24e-15 ✓ sig.
Staphylococcus aureus infection
C1QA, C1QB, C1QC, C1R, C1S, C2, C4A, C4B
 KEGG 8 / 99 121× 1.60e-17 7.90e-15 ✓ sig.
Classical antibody-mediated complement activation
C1QA, C1QB, C1QC, C1R, C1S
 Reactome 5 / 6 1,251× 1.61e-16 6.46e-14 ✓ sig.
Systemic lupus erythematosus
C1QA, C1QB, C1QC, C1R, C1S, C2, C4A, C4B
 KEGG 8 / 140 85.8× 2.79e-16 1.08e-13 ✓ sig.
Coronavirus disease - COVID-19
C1QA, C1QB, C1QC, C1R, C1S, C2, C4A, C4B
 KEGG 8 / 238 50.5× 2.12e-14 5.65e-12 ✓ sig.
Alcoholic liver disease
C1QA, C1QB, C1QC, C2, C4A, C4B
 KEGG 6 / 144 62.6× 7.35e-11 8.97e-9 ✓ sig.
Activation of C3 and C5
C2, C4A, C4B
 Reactome 3 / 8 563× 1.08e-8 7.96e-7 ✓ sig.
Chagas disease
C1QA, C1QB, C1QC
 KEGG 3 / 103 43.7× 3.33e-5 7.90e-4 ✓ sig.
Efferocytosis
C1QA, C1QB, C1QC
 KEGG 3 / 157 28.7× 1.17e-4 2.14e-3 ✓ sig.
Prion disease
C1QA, C1QB, C1QC
 KEGG 3 / 275 16.4× 6.11e-4 7.81e-3 ✓ sig.
Post-translational protein phosphorylation
C4A, C4B
 Reactome 2 / 108 27.8× 2.17e-3 2.02e-2 ✓ sig.
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
C4A, C4B
 Reactome 2 / 125 24.0× 2.89e-3 2.48e-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 ⇵
complement activation, classical pathway
C1QA, C1QB, C1QC, C1R, C1S, C2, C4A, C4B
 GO:0006958 8 / 37 505× 1.05e-22 2.45e-19 ✓ sig.
complement activation
C1QA, C1QB, C1R, C1S, C2, C4A, C4B
 GO:0006956 7 / 35 467× 3.41e-19 4.84e-16 ✓ sig.
opsonization
C1R, C1S, C2, C4A, C4B
 GO:0008228 5 / 18 649× 2.52e-14 1.62e-11 ✓ sig.
innate immune response
C1QA, C1QB, C1QC, C1R, C1S, C2, C4A, C4B
 GO:0045087 8 / 605 30.9× 1.15e-12 5.41e-10 ✓ sig.
activation of membrane attack complex
C1R, C1S, C2, C4A
 GO:0001905 4 / 13 719× 9.84e-12 3.77e-9 ✓ sig.
immune system process
C1QA, C1QB, C1QC, C1R, C1S, C2, C4A, C4B
 GO:0002376 8 / 943 19.8× 4.09e-11 1.37e-8 ✓ sig.
positive regulation of apoptotic cell clearance
C2, C4A, C4B
 GO:2000427 3 / 6 1,168× 1.03e-9 2.38e-7 ✓ sig.
synapse pruning
C1QA, C1QB, C1QC
 GO:0098883 3 / 7 1,001× 1.80e-9 3.88e-7 ✓ sig.
complement activation, GZMK pathway
C2, C4A, C4B
 GO:0160257 3 / 12 584× 1.13e-8 1.96e-6 ✓ sig.
killing of cells of another organism
C1R, C1S, C2, C4A
 GO:0031640 4 / 104 89.8× 6.23e-8 8.54e-6 ✓ sig.
protein maturation
C1R, C1S, C2, C4A
 GO:0051604 4 / 134 69.7× 1.73e-7 2.00e-5 ✓ sig.
complement activation, lectin pathway
C2, C4A
 GO:0001867 2 / 13 359× 1.25e-5 6.46e-4 ✓ sig.
zymogen activation
C1R, C1S
 GO:0031638 2 / 32 146× 7.90e-5 2.60e-3 ✓ sig.
vertebrate eye-specific patterning
C1QA
 GO:0150064 1 / 3 779× 1.28e-3 1.67e-2 ✓ sig.
detection of molecule of bacterial origin
C4B
 GO:0032490 1 / 3 779× 1.28e-3 1.67e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Complement pathway abnormality Immunodeficiency due to a classical component pathway complement deficiency 0.444 4 2.92e-14 3.41e-13 ✓ sig.
C1q deficiency Complement pathway abnormality 0.333 3 9.05e-11 8.46e-10 ✓ sig.
C1q deficiency Immunodeficiency due to a classical component pathway complement deficiency 0.333 2 1.50e-7 1.02e-6 ✓ sig.
Complement pathway abnormality Periodontal ehlers-danlos syndrome 0.222 2 2.33e-7 1.55e-6 ✓ sig.
C1s deficiency Periodontal ehlers-danlos syndrome 0.333 1 1.29e-4 3.27e-4 ✓ sig.
C1q deficiency Systemic lupus erythematosus related to C1QA 0.250 1 1.94e-4 4.41e-4 ✓ sig.
C1q deficiency Immunodeficiency due to an early component of complement deficiency 0.250 1 1.94e-4 4.41e-4 ✓ sig.
C4a deficiency Immunodeficiency due to a classical component pathway complement deficiency 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Immunodeficiency due to a classical component pathway complement deficiency Systemic lupus erythematosus related to C1QA 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Immunodeficiency due to a classical component pathway complement deficiency Periodontal ehlers-danlos syndrome 0.167 1 5.16e-4 9.13e-4 ✓ sig.
C1s deficiency Complement pathway abnormality 0.111 1 5.17e-4 9.13e-4 ✓ sig.
C4a deficiency Complement pathway abnormality 0.111 1 5.17e-4 9.13e-4 ✓ sig.
Complement pathway abnormality Immunodeficiency due to an early component of complement deficiency 0.111 1 5.17e-4 9.13e-4 ✓ sig.
Complement pathway abnormality Systemic lupus erythematosus related to C1QA 0.111 1 5.17e-4 9.13e-4 ✓ sig.