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 391

5 diseases · 7 shared-gene connections
5 Diseases
66 Unique genes
0.212 Avg. similarity score
Calcinosis 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 ⇵
Calcinosis 4 4 46
Heart valve disease 3 3 41
Heart valve prolapse 3 3 29
Vitamin k deficiency 3 3 1
Hereditary arterial and articular multiple calcification syndrome 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
BGLAP 4 / 5 Calcinosis, Heart valve disease, Heart valve prolapse, Vitamin k deficiency
C6 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
CASP3 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
CCL2 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
COL18A1 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
COL1A1 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
FCGR1A 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
IL18 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
IL1B 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
ITGB2 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
JAK2 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
LCN2 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
LSP1 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
LY86 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
NOTCH1 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
PTPN6 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
PYCARD 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
RIPK3 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
SPN 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
SPP1 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
TIMP1 3 / 5 Calcinosis, Heart valve disease, Heart valve prolapse
ACE 2 / 5 Heart valve disease, Heart valve prolapse
ADAMTS19 2 / 5 Heart valve disease, Heart valve prolapse
ADAMTSL2 2 / 5 Heart valve disease, Heart valve prolapse
CCL15 2 / 5 Heart valve disease, Heart valve prolapse
COL1A2 2 / 5 Heart valve disease, Heart valve prolapse
FGFR1 2 / 5 Heart valve disease, Heart valve prolapse
HTR2B 2 / 5 Heart valve disease, Heart valve prolapse
NT5E 2 / 5 Calcinosis, Hereditary arterial and articular multiple calcification syndrome
PCDHA9 2 / 5 Heart valve disease, Heart valve prolapse
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 ⇵
Interleukin-4 and Interleukin-13 signaling
CCL2, IL18, IL1B, ITGB1, ITGB2, JAK2, LCN2, MMP2, MMP9, POMC, TGFB1, TIMP1
 Reactome 15 / 108 25.3× 1.37e-17 7.24e-15 ✓ sig.
AGE-RAGE signaling pathway in diabetic complications
CASP3, CCL2, COL1A1, IL1B, JAK2, MMP2, TGFB1, TNF, COL1A2
 KEGG 9 / 101 16.2× 3.65e-9 3.56e-7 ✓ sig.
Leishmaniasis
FCGR1A, IL1B, ITGB1, ITGB2, JAK2, PTPN6, TGFB1, TNF
 KEGG 8 / 78 18.7× 9.30e-9 8.19e-7 ✓ sig.
Proteoglycans in cancer
CASP3, COL1A1, ITGB1, MMP2, MMP9, PTPN6, TGFB1, TNF, TP53, COL1A2, FGFR1
 KEGG 11 / 204 9.8× 1.23e-8 1.04e-6 ✓ sig.
Pathways in cancer
BMP2, CASP3, EPO, FGF23, ITGB1, JAK2, MMP2, MMP9, NOTCH1, PDGFB, PDGFRB, TGFB1
 KEGG 16 / 533 5.5× 1.97e-8 1.59e-6 ✓ sig.
FGFR1c and Klotho ligand binding and activation
FGF23, KL, FGFR1
 Reactome 3 / 3 182× 1.59e-7 9.76e-6 ✓ sig.
Malaria
CCL2, IL18, IL1B, ITGB2, TGFB1, TNF
 KEGG 6 / 50 21.8× 2.87e-7 1.64e-5 ✓ sig.
PI3K-Akt signaling pathway
COL1A1, EPO, FGF23, ITGB1, JAK2, PDGFB, PDGFRB, SPP1, TP53, CDK6, COL1A2, FGFR1
 KEGG 12 / 361 6.0× 5.17e-7 2.75e-5 ✓ sig.
Legionellosis
CASP3, IL18, IL1B, ITGB2, PYCARD, TNF
 KEGG 6 / 56 19.5× 5.72e-7 3.00e-5 ✓ sig.
Tuberculosis
CASP3, FCGR1A, IL18, IL1B, ITGB2, JAK2, LSP1, TGFB1, TNF
 KEGG 9 / 181 9.0× 5.81e-7 3.05e-5 ✓ sig.
Activation of Matrix Metalloproteinases
COL18A1, MMP2, MMP9, TIMP1, TIMP2
 Reactome 5 / 33 27.6× 9.05e-7 4.47e-5 ✓ sig.
Amoebiasis
CASP3, COL1A1, IL1B, ITGB2, TGFB1, TNF, COL1A2
 KEGG 7 / 103 12.4× 1.43e-6 6.66e-5 ✓ sig.
Lipid and atherosclerosis
CASP3, CCL2, IL18, IL1B, JAK2, MMP9, PYCARD, TNF, TP53
 KEGG 9 / 216 7.6× 2.54e-6 1.08e-4 ✓ sig.
Melanoma
FGF23, PDGFB, PDGFRB, TP53, CDK6, FGFR1
 KEGG 6 / 73 15.0× 2.79e-6 1.17e-4 ✓ sig.
Pertussis
CASP3, IL1B, ITGB1, ITGB2, PYCARD, TNF
 KEGG 6 / 78 14.0× 4.12e-6 1.62e-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 ⇵
positive regulation of cell migration
BMP2, CCL2, COL1A1, IL1B, ITGB1, JAK2, MMP2, NOTCH1, PDGFB, PDGFRB, SNAI2, TGFB1
 GO:0030335 14 / 292 13.6× 1.42e-12 6.31e-10 ✓ sig.
positive regulation of ERK1 and ERK2 cascade
BMP2, EPO, FGF23, IL1B, NOTCH1, PDGFB, PDGFRB, PYCARD, TGFB1, TNF, HTR2B
 GO:0070374 11 / 201 15.5× 1.09e-10 3.10e-8 ✓ sig.
response to macrophage colony-stimulating factor
ALPL, BGLAP, SPP1, TNF
 GO:0036005 4 / 4 283× 1.42e-10 3.94e-8 ✓ sig.
response to xenobiotic stimulus
BGLAP, CASP3, COL18A1, COL1A1, LCN2, MMP2, TGFB1, TNF, TP53, GABRG3, HTR2B
 GO:0009410 11 / 248 12.6× 1.02e-9 2.27e-7 ✓ sig.
positive regulation of apoptotic process
BMP2, CASP3, ITGB1, JAK2, LCN2, MMP2, MMP9, NOTCH1, PYCARD, TGFB1, TNF, TP53
 GO:0043065 12 / 326 10.4× 1.38e-9 2.99e-7 ✓ sig.
skeletal system development
AHSG, ALPL, BGLAP, BMP2, COL18A1, COL1A1, MMP9, COL1A2, FGFR1
 GO:0001501 9 / 151 16.9× 2.89e-9 5.71e-7 ✓ sig.
positive regulation of cell population proliferation
BMP2, EPO, FGF23, IL1B, JAK2, NOTCH1, PDGFB, PDGFRB, PTPN6, TGFB1, TIMP1, FGFR1
 GO:0008284 14 / 532 7.5× 3.85e-9 7.41e-7 ✓ sig.
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
IL18, IL1B, ITGB1, JAK2, PDGFB, PDGFRB, PTPN6, TGFB1, TNF, FGFR1
 GO:0051897 10 / 217 13.0× 4.34e-9 8.20e-7 ✓ sig.
positive regulation of DNA-templated transcription
BMP2, COL1A1, EPO, FGF23, IL1B, NOTCH1, NR1I2, PDGFB, RIPK3, SPP1, TGFB1, TNF
 GO:0045893 16 / 778 5.8× 8.51e-9 1.49e-6 ✓ sig.
response to vitamin D
ALPL, BGLAP, KL, SPP1, TGFB1
 GO:0033280 5 / 21 67.4× 9.17e-9 1.59e-6 ✓ sig.
positive regulation of smooth muscle cell proliferation
IL18, MMP2, PDGFB, PDGFRB, TGFB1, TNF
 GO:0048661 6 / 52 32.7× 2.76e-8 4.09e-6 ✓ sig.
positive regulation of reactive oxygen species metabolic process
LCN2, PDGFB, PDGFRB, RIPK3, TP53
 GO:2000379 5 / 34 41.6× 1.21e-7 1.41e-5 ✓ sig.
smooth muscle adaptation
IL1B, PDGFB, PDGFRB
 GO:0014805 3 / 4 212× 1.68e-7 1.87e-5 ✓ sig.
positive regulation of gene expression
BMP2, CCL2, IL18, IL1B, LCN2, NOTCH1, NR1I2, PDGFB, TGFB1, TNF, TP53, CDK6
 GO:0010628 12 / 504 6.7× 1.70e-7 1.89e-5 ✓ sig.
apoptotic process
CASP3, EPO, GALNT3, IL1B, ITGB2, JAK2, LCN2, MMP9, NOTCH1, PYCARD, RIPK3, TGFB1
 GO:0006915 14 / 747 5.3× 2.65e-7 2.74e-5 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Heart valve disease Heart valve prolapse 0.690 29 2.62e-81 2.21e-79 ✓ sig.
Calcinosis Heart valve prolapse 0.382 21 1.76e-49 9.67e-48 ✓ sig.
Calcinosis Heart valve disease 0.313 21 1.09e-44 5.36e-43 ✓ sig.
Heart valve prolapse Vitamin k deficiency 0.033 1 1.88e-3 2.75e-3 ✓ sig.
Heart valve disease Vitamin k deficiency 0.024 1 2.66e-3 3.58e-3 ✓ sig.
Calcinosis Hereditary arterial and articular multiple calcification syndrome 0.021 1 2.99e-3 3.94e-3 ✓ sig.
Calcinosis Vitamin k deficiency 0.021 1 2.99e-3 3.94e-3 ✓ sig.