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 76

12 diseases · 21 shared-gene connections
12 Diseases
81 Unique genes
0.110 Avg. similarity score
Cachexia Most-connected disease (7 links)
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Disease Searched: Hepatolenticular degeneration 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 ⇵
Cachexia 7 7 12
Alcoholic hepatitis 6 6 5
Autoimmune uveitis 5 5 1
Esotropia 5 5 10
Angina pectoris 4 4 12
Hepatolenticular degeneration 4 4 27
Oral submucous fibrosis 4 4 20
Delirium 3 3 10
ALG11-congenital disorder of glycosylation 1 1 1
Chondromalacia 1 1 8
X-linked ichthyosis with steryl-sulfatase deficiency 1 1 1
lymphoproliferative syndrome 2 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
CXCL8 8 / 12 Alcoholic hepatitis, Angina pectoris, Autoimmune uveitis, Cachexia and 4 more
TNF 6 / 12 Alcoholic hepatitis, Angina pectoris, Cachexia, Esotropia and 2 more
IL6 4 / 12 Cachexia, Delirium, Hepatolenticular degeneration, Oral submucous fibrosis
PTGS2 3 / 12 Cachexia, Esotropia, Oral submucous fibrosis
ALG11 2 / 12 ALG11-congenital disorder of glycosylation, Hepatolenticular degeneration
APOE 2 / 12 Delirium, Hepatolenticular degeneration
CD27 2 / 12 Cachexia, lymphoproliferative syndrome 2
IGF1 2 / 12 Cachexia, Delirium
LOX 2 / 12 Hepatolenticular degeneration, Oral submucous fibrosis
MMP1 2 / 12 Angina pectoris, Oral submucous fibrosis
MMP9 2 / 12 Angina pectoris, Oral submucous fibrosis
STS 2 / 12 Alcoholic hepatitis, X-linked ichthyosis with steryl-sulfatase deficiency
SULT1E1 2 / 12 Alcoholic hepatitis, Chondromalacia
TIMP1 2 / 12 Hepatolenticular degeneration, Oral submucous fibrosis
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
MMP9, TNF, CXCL8, MMP1, IL6, PTGS2, LIF, IL4R, IL10, TIMP1, COL1A2, FGF2
 Reactome 15 / 108 20.6× 3.72e-16 1.47e-13 ✓ sig.
Interleukin-10 signaling
TNF, CXCL8, IL6, PTGS2, TNFRSF1A, IL1RN, LIF, CCL5, IL10, TIMP1
 Reactome 10 / 47 31.5× 4.65e-13 1.06e-10 ✓ sig.
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
MMP1, PAPPA, SERPINC1, IGF1, IL6, APOE, CP, TIMP1, CST3, MMP2
 Reactome 10 / 125 11.9× 1.04e-8 9.51e-7 ✓ sig.
Proteoglycans in cancer
PLAU, MMP9, TLR4, TNF, ITGA2, IGF1, CAMK2A, COL1A1, COL1A2, FGF2, MMP2, TGFB1
 KEGG 12 / 204 8.7× 1.06e-8 9.61e-7 ✓ sig.
Rheumatoid arthritis
TLR4, TNF, CXCL8, MMP1, IL6, CCL5, CTLA4, IFNG, TGFB1
 KEGG 9 / 95 14.0× 1.35e-8 1.19e-6 ✓ sig.
Lipid and atherosclerosis
MMP9, TLR4, TNF, CXCL8, MMP1, IL6, TNFRSF1A, SOD2, CCL5, CAMK2A, PPP3CA, PPP3CB
 KEGG 12 / 216 8.2× 2.00e-8 1.69e-6 ✓ sig.
Chagas disease
TLR4, TNF, CXCL8, IL6, TNFRSF1A, CCL5, IL10, IFNG, TGFB1
 KEGG 9 / 103 13.0× 2.75e-8 2.24e-6 ✓ sig.
Amoebiasis
TLR4, TNF, CXCL8, IL6, IL10, COL1A1, COL1A2, IFNG, TGFB1
 KEGG 9 / 103 13.0× 2.75e-8 2.24e-6 ✓ sig.
Malaria
TLR4, TNF, CXCL8, IL6, IL10, IFNG, TGFB1
 KEGG 7 / 50 20.8× 3.86e-8 2.99e-6 ✓ sig.
Cytokine-cytokine receptor interaction
TNF, CXCL8, CD27, GDF15, IL6, TNFRSF1A, IL1RN, LIF, IL4R, CCL5, IL10, IFNG
 KEGG 13 / 298 6.5× 8.61e-8 6.17e-6 ✓ sig.
Inflammatory bowel disease
TLR4, TNF, IL6, IL4R, IL10, IFNG, TGFB1
 KEGG 7 / 66 15.7× 2.76e-7 1.70e-5 ✓ sig.
Tuberculosis
TLR4, TNF, IL6, TNFRSF1A, CAMK2A, IL10, PPP3CA, PPP3CB, IFNG, TGFB1
 KEGG 10 / 181 8.2× 3.51e-7 2.10e-5 ✓ sig.
Pathways in cancer
MMP9, CXCL8, ITGA2, MMP1, IGF1, IL6, PTGS2, IL4R, CAMK2A, FGF2, GSTM1, GSTT1
 KEGG 15 / 533 4.2× 2.27e-6 1.06e-4 ✓ sig.
IL-17 signaling pathway
MMP9, TNF, CXCL8, MMP1, IL6, PTGS2, IFNG
 KEGG 7 / 94 11.0× 3.12e-6 1.38e-4 ✓ sig.
AGE-RAGE signaling pathway in diabetic complications
TNF, CXCL8, IL6, COL1A1, COL1A2, MMP2, TGFB1
 KEGG 7 / 101 10.3× 5.04e-6 2.04e-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 smooth muscle cell proliferation
TLR4, TNF, ITGA2, IGF1, IL6, CCL5, FGF2, MMP2, TGFB1
 GO:0048661 9 / 52 39.9× 1.08e-12 4.98e-10 ✓ sig.
response to xenobiotic stimulus
AVP, TNF, ITGA2, DRD2, DRD3, SLC6A3, SOD2, IL10, LOX, SNCA, COL1A1, MMP2
 GO:0009410 13 / 248 12.1× 4.88e-11 1.53e-8 ✓ sig.
response to ethanol
AVP, TNF, CD27, DRD2, DRD3, SLC6A3, TH, FGF2, TGFB1
 GO:0045471 9 / 110 18.9× 1.12e-9 2.48e-7 ✓ sig.
response to hypoxia
PLAU, TNF, ITGA2, DRD2, LIF, TH, SOD2, LOXL2, MMP2, TGFB1
 GO:0001666 10 / 176 13.1× 4.48e-9 8.40e-7 ✓ sig.
negative regulation of apoptotic process
AVP, MMP9, TNF, CD27, GHRL, IGF1, IL6, PTGS2, SOD2, TFAP2A, ANXA5, IL10
 GO:0043066 15 / 524 6.6× 6.33e-9 1.14e-6 ✓ sig.
positive regulation of nitric oxide biosynthetic process
TLR4, TNF, PTGS2, APOE, SOD2, IFNG
 GO:0045429 6 / 42 33.0× 2.54e-8 3.84e-6 ✓ sig.
positive regulation of receptor signaling pathway via STAT
IL6, LIF, CCL5, TGFB1
 GO:1904894 4 / 9 103× 4.06e-8 5.71e-6 ✓ sig.
immune response
TLR4, TNF, CXCL8, IL6, IL1RN, LIF, IL4R, CCL5, HAMP, IL10, CST3, CTLA4
 GO:0006955 14 / 543 5.9× 7.90e-8 1.01e-5 ✓ sig.
cellular response to UV-A
MMP9, MMP1, TIMP1, MMP2
 GO:0071492 4 / 11 83.9× 1.06e-7 1.29e-5 ✓ sig.
positive regulation of vascular associated smooth muscle cell proliferation
MMP9, TNF, IGF1, IL10, FGF2, MMP2
 GO:1904707 6 / 53 26.1× 1.07e-7 1.30e-5 ✓ sig.
cell surface receptor signaling pathway via STAT
IGF1, IL6, LIF, CCL5, IFNG
 GO:0097696 5 / 28 41.2× 1.23e-7 1.46e-5 ✓ sig.
cellular response to fibroblast growth factor stimulus
CXCL8, ZFP36, CCL5, SNCA, COL1A1
 GO:0044344 5 / 33 35.0× 2.91e-7 3.06e-5 ✓ sig.
synaptic transmission, dopaminergic
DRD2, DRD3, TH, SNCA
 GO:0001963 4 / 15 61.5× 4.31e-7 4.24e-5 ✓ sig.
negative regulation of cell population proliferation
TNF, CXCL8, IGF1, IL6, PTHLH, DRD2, LIF, SOD2, TFAP2A, IL10, FGF2, TGFB1
 GO:0008285 12 / 444 6.2× 4.48e-7 4.38e-5 ✓ sig.
positive regulation of smooth muscle cell migration
TLR4, ITGA2, IGF1, CCL5
 GO:0014911 4 / 17 54.3× 7.47e-7 6.68e-5 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Hepatolenticular degeneration Oral submucous fibrosis 0.116 5 1.71e-10 1.66e-9 ✓ sig.
Angina pectoris Oral submucous fibrosis 0.138 4 1.02e-9 9.21e-9 ✓ sig.
Cachexia Oral submucous fibrosis 0.138 4 1.02e-9 9.21e-9 ✓ sig.
Cachexia Delirium 0.150 3 4.33e-8 3.23e-7 ✓ sig.
Cachexia Esotropia 0.150 3 4.33e-8 3.23e-7 ✓ sig.
Esotropia Oral submucous fibrosis 0.107 3 2.24e-7 1.48e-6 ✓ sig.
Delirium Hepatolenticular degeneration 0.086 3 5.72e-7 3.50e-6 ✓ sig.
Cachexia Hepatolenticular degeneration 0.081 3 1.05e-6 6.15e-6 ✓ sig.
Alcoholic hepatitis Esotropia 0.143 2 3.79e-6 2.01e-5 ✓ sig.
Alcoholic hepatitis Angina pectoris 0.125 2 5.56e-6 2.87e-5 ✓ sig.
Alcoholic hepatitis Cachexia 0.125 2 5.56e-6 2.87e-5 ✓ sig.
Angina pectoris Esotropia 0.095 2 2.50e-5 1.17e-4 ✓ sig.
Alcoholic hepatitis X-linked ichthyosis with steryl-sulfatase deficiency 0.167 1 3.25e-4 7.71e-4 ✓ sig.
Alcoholic hepatitis Autoimmune uveitis 0.167 1 3.25e-4 7.71e-4 ✓ sig.
Autoimmune uveitis Esotropia 0.091 1 6.49e-4 1.24e-3 ✓ sig.
Autoimmune uveitis Delirium 0.091 1 6.49e-4 1.24e-3 ✓ sig.
Cachexia lymphoproliferative syndrome 2 0.077 1 7.79e-4 1.41e-3 ✓ sig.
Autoimmune uveitis Cachexia 0.077 1 7.79e-4 1.41e-3 ✓ sig.
Angina pectoris Autoimmune uveitis 0.077 1 7.79e-4 1.41e-3 ✓ sig.
ALG11-congenital disorder of glycosylation Hepatolenticular degeneration 0.036 1 1.75e-3 2.61e-3 ✓ sig.
Alcoholic hepatitis Chondromalacia 0.077 1 2.60e-3 3.51e-3 ✓ sig.