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 43

16 diseases · 24 shared-gene connections
16 Diseases
125 Unique genes
0.102 Avg. similarity score
Cachexia Most-connected disease (7 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 ⇵
Cachexia 7 7 12
Alcoholic hepatitis 6 6 5
Angina pectoris 5 5 12
Esotropia 5 5 10
Oral submucous fibrosis 5 5 20
Autoimmune uveitis 4 4 1
Colitis 4 4 33
Hepatolenticular degeneration 3 3 27
Sepsis 2 2 34
ALG11-congenital disorder of glycosylation 1 1 1
Chondromalacia 1 1 8
Dysbiosis 1 1 1
X-linked ichthyosis with steryl-sulfatase deficiency 1 1 1
inflammatory skin and bowel disease, neonatal, 1 1 1 1
lymphoproliferative syndrome 2 1 1 1
thrombocytopenia 6 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
TNF 8 / 16 Alcoholic hepatitis, Angina pectoris, Cachexia, Colitis and 4 more
CXCL8 7 / 16 Alcoholic hepatitis, Angina pectoris, Autoimmune uveitis, Cachexia and 3 more
IL6 5 / 16 Cachexia, Colitis, Hepatolenticular degeneration, Oral submucous fibrosis and 1 more
PTGS2 4 / 16 Cachexia, Colitis, Esotropia, Oral submucous fibrosis
IFNG 3 / 16 Colitis, Oral submucous fibrosis, Sepsis
IL10 3 / 16 Colitis, Hepatolenticular degeneration, Sepsis
MMP9 3 / 16 Angina pectoris, Oral submucous fibrosis, Sepsis
TLR4 3 / 16 Angina pectoris, Dysbiosis, Sepsis
ADAM17 2 / 16 Colitis, inflammatory skin and bowel disease, neonatal, 1
ALG11 2 / 16 ALG11-congenital disorder of glycosylation, Hepatolenticular degeneration
CD27 2 / 16 Cachexia, lymphoproliferative syndrome 2
GHRL 2 / 16 Cachexia, Colitis
IGF1 2 / 16 Cachexia, Colitis
IL1B 2 / 16 Colitis, Sepsis
LOX 2 / 16 Hepatolenticular degeneration, Oral submucous fibrosis
MIF 2 / 16 Colitis, Sepsis
MMP1 2 / 16 Angina pectoris, Oral submucous fibrosis
NOS2 2 / 16 Colitis, Sepsis
SRC 2 / 16 Colitis, thrombocytopenia 6
STS 2 / 16 Alcoholic hepatitis, X-linked ichthyosis with steryl-sulfatase deficiency
SULT1E1 2 / 16 Alcoholic hepatitis, Chondromalacia
TGFB1 2 / 16 Oral submucous fibrosis, Sepsis
TIMP1 2 / 16 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, ALOX5, HMOX1, IL10, IL17A, IL1B, IL4
 Reactome 21 / 108 18.7× 2.37e-21 2.35e-18 ✓ sig.
Lipid and atherosclerosis
MMP9, TLR4, TNF, CXCL8, MMP1, IL6, TNFRSF1A, APOA4, IL1B, RELA, SRC, SOD2
 KEGG 23 / 216 10.2× 3.42e-17 1.65e-14 ✓ sig.
Tuberculosis
TLR4, TNF, IL6, TNFRSF1A, IFNG, IL10, IL1B, NOS2, RELA, SRC, SYK, CAMK2A
 KEGG 20 / 181 10.6× 2.30e-15 8.22e-13 ✓ sig.
IL-17 signaling pathway
MMP9, TNF, CXCL8, MMP1, IL6, PTGS2, IFNG, IL17A, IL1B, IL4, RELA, CASP3
 KEGG 15 / 94 15.3× 3.60e-14 9.96e-12 ✓ sig.
Chagas disease
TLR4, TNF, CXCL8, IL6, TNFRSF1A, IFNG, IL10, IL1B, NOS2, RELA, SERPINE1, CCL5
 KEGG 15 / 103 14.0× 1.46e-13 3.60e-11 ✓ sig.
AGE-RAGE signaling pathway in diabetic complications
TNF, CXCL8, IL6, IL1B, RELA, SERPINE1, COL1A1, COL1A2, MMP2, TGFB1, CASP3, MAPK1
 KEGG 14 / 101 13.3× 2.00e-12 4.13e-10 ✓ sig.
HIF-1 signaling pathway
TLR4, IGF1, IL6, HMOX1, IFNG, NOS2, RELA, SERPINE1, CAMK2A, TIMP1, ANGPT1, MAPK1
 KEGG 14 / 110 12.2× 6.61e-12 1.23e-9 ✓ sig.
Kaposi sarcoma-associated herpesvirus infection
CXCL8, IL6, PTGS2, TNFRSF1A, ZFP36, HLA-B, RELA, SRC, SYK, PPP3CA, PPP3CB, FGF2
 KEGG 17 / 196 8.3× 1.76e-11 2.99e-9 ✓ sig.
TNF signaling pathway
MMP9, TNF, IL6, PTGS2, TNFRSF1A, ADAM17, IL1B, RELA, CCL5, CASP3, LTA, MAPK1
 KEGG 14 / 119 11.3× 1.97e-11 3.30e-9 ✓ sig.
Pertussis
TLR4, TNF, CXCL8, IL6, IL10, IL1B, NOS2, RELA, CASP3, MAPK1, MAPK3, NLRP3
 KEGG 12 / 78 14.8× 2.30e-11 3.79e-9 ✓ sig.
Leishmaniasis
TLR4, TNF, PTGS2, IFNG, IL10, IL1B, IL4, NOS2, RELA, TGFB1, MAPK1, MAPK3
 KEGG 12 / 78 14.8× 2.30e-11 3.79e-9 ✓ sig.
Proteoglycans in cancer
PLAU, MMP9, TLR4, TNF, ITGA2, IGF1, SRC, TIMP3, CAMK2A, COL1A1, COL1A2, FGF2
 KEGG 17 / 204 8.0× 3.34e-11 5.35e-9 ✓ sig.
Interleukin-10 signaling
TNF, CXCL8, IL6, PTGS2, TNFRSF1A, IL10, IL1B, CCL5, TIMP1, CSF3
 Reactome 10 / 47 20.4× 3.88e-11 6.14e-9 ✓ sig.
Amoebiasis
TLR4, TNF, CXCL8, IL6, IFNG, IL10, IL1B, NOS2, RELA, COL1A1, COL1A2, TGFB1
 KEGG 13 / 103 12.1× 4.33e-11 6.78e-9 ✓ sig.
C-type lectin receptor signaling pathway
TNF, IL6, PTGS2, IL10, IL1B, RELA, SRC, SYK, PPP3CA, PPP3CB, MAPK1, MAPK3
 KEGG 13 / 105 11.9× 5.55e-11 8.42e-9 ✓ 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 ⇵
response to lipopolysaccharide
TLR4, TNF, ADAM17, IL10, IL1B, MPO, NOS2, RELA, SOD2, SNCA, CASP3, LBP
 GO:0032496 17 / 161 15.8× 6.04e-16 4.95e-13 ✓ sig.
negative regulation of apoptotic process
AVP, MMP9, TNF, CD27, GHRL, IGF1, IL6, PTGS2, GCG, IL10, IL4, MIF
 GO:0043066 26 / 524 7.4× 9.02e-16 7.08e-13 ✓ sig.
positive regulation of chemokine production
TLR4, TNF, IL6, ADAM17, HMOX1, IFNG, IL1B, IL4R, ADORA2B, HMGB1, LBP
 GO:0032722 11 / 49 33.6× 1.80e-14 1.12e-11 ✓ sig.
positive regulation of interleukin-6 production
TLR4, TNF, IL6, IFNG, IL17A, IL1B, NOS2, RELA, SYK, TGFB1, ADORA2B, HMGB1
 GO:0032755 13 / 103 18.9× 1.83e-13 9.65e-11 ✓ sig.
positive regulation of ERK1 and ERK2 cascade
TLR4, TNF, IGF1, FGF19, GCG, IL1B, MIF, NAMPT, SRC, APOE, FGF2, TGFB1
 GO:0070374 16 / 201 11.9× 3.92e-13 1.94e-10 ✓ sig.
positive regulation of smooth muscle cell proliferation
TLR4, TNF, ITGA2, IGF1, IL6, HMOX1, CCL5, FGF2, MMP2, TGFB1
 GO:0048661 10 / 52 28.7× 1.55e-12 6.81e-10 ✓ sig.
cellular response to lipopolysaccharide
MMP9, TLR4, TNF, CXCL8, IL6, ZFP36, IL10, IL1B, NOS2, RELA, SERPINE1, CSF3
 GO:0071222 15 / 187 12.0× 1.99e-12 8.55e-10 ✓ sig.
inflammatory response
TLR4, TNF, CXCL8, IL6, TNFRSF1A, ALOX5, IL17A, IL1B, MIF, NAMPT, NOS2, RELA
 GO:0006954 21 / 467 6.7× 4.69e-12 1.85e-9 ✓ sig.
response to xenobiotic stimulus
AVP, TNF, ITGA2, ADAM17, AHR, IL10, RELA, SOD2, LOX, SNCA, COL1A1, MMP2
 GO:0009410 16 / 248 9.6× 9.82e-12 3.62e-9 ✓ sig.
immune response
TLR4, TNF, CXCL8, IL6, HLA-B, IFNG, IL10, IL17A, IL1B, IL4, MADCAM1, IL4R
 GO:0006955 22 / 543 6.1× 1.07e-11 3.91e-9 ✓ sig.
positive regulation of interleukin-8 production
TLR4, TNF, IL6, IL1B, NOS2, RELA, SYK, SERPINE1, HMGB1, LBP
 GO:0032757 10 / 65 23.0× 1.63e-11 5.72e-9 ✓ sig.
regulation of insulin secretion
TNF, IL6, ALOX5, GCG, IFNG, IL1B, NOS2, CCL5, PPP3CB
 GO:0050796 9 / 46 29.2× 1.79e-11 6.20e-9 ✓ sig.
positive regulation of neuroinflammatory response
TNF, IL6, IL1B, CCL5, MAPK1, MAPK3
 GO:0150078 6 / 16 56.1× 6.02e-10 1.43e-7 ✓ sig.
positive regulation of cell population proliferation
AVP, IGF1, IL6, PTHLH, ADAM17, FGF19, IFNG, IL1B, IL4, MIF, NAMPT, RELA
 GO:0008284 19 / 532 5.3× 2.57e-9 5.15e-7 ✓ sig.
positive regulation of tumor necrosis factor production
TLR4, IL6, ADAM17, IFNG, IL17A, MIF, SYK, TGFB1, HMGB1, LBP
 GO:0032760 10 / 113 13.2× 4.33e-9 8.19e-7 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Colitis Sepsis 0.115 7 5.43e-13 7.11e-12 ✓ sig.
Cachexia Colitis 0.122 5 2.58e-11 2.89e-10 ✓ sig.
Hepatolenticular degeneration Oral submucous fibrosis 0.116 5 1.71e-10 1.76e-9 ✓ sig.
Oral submucous fibrosis Sepsis 0.100 5 5.85e-10 5.72e-9 ✓ sig.
Angina pectoris Oral submucous fibrosis 0.138 4 1.02e-9 9.75e-9 ✓ sig.
Cachexia Oral submucous fibrosis 0.138 4 1.02e-9 9.75e-9 ✓ sig.
Cachexia Esotropia 0.150 3 4.33e-8 3.41e-7 ✓ sig.
Esotropia Oral submucous fibrosis 0.107 3 2.24e-7 1.56e-6 ✓ sig.
Cachexia Hepatolenticular degeneration 0.081 3 1.05e-6 6.49e-6 ✓ sig.
Alcoholic hepatitis Esotropia 0.143 2 3.79e-6 2.12e-5 ✓ sig.
Alcoholic hepatitis Angina pectoris 0.125 2 5.56e-6 3.03e-5 ✓ sig.
Alcoholic hepatitis Cachexia 0.125 2 5.56e-6 3.03e-5 ✓ sig.
Angina pectoris Esotropia 0.095 2 2.50e-5 1.23e-4 ✓ sig.
Alcoholic hepatitis X-linked ichthyosis with steryl-sulfatase deficiency 0.167 1 3.25e-4 7.58e-4 ✓ sig.
Alcoholic hepatitis Autoimmune uveitis 0.167 1 3.25e-4 7.58e-4 ✓ sig.
Autoimmune uveitis Esotropia 0.091 1 6.49e-4 1.22e-3 ✓ sig.
Autoimmune uveitis Cachexia 0.077 1 7.79e-4 1.39e-3 ✓ sig.
Angina pectoris Dysbiosis 0.077 1 7.79e-4 1.39e-3 ✓ sig.
Angina pectoris Autoimmune uveitis 0.077 1 7.79e-4 1.39e-3 ✓ sig.
Cachexia lymphoproliferative syndrome 2 0.077 1 7.79e-4 1.39e-3 ✓ sig.
ALG11-congenital disorder of glycosylation Hepatolenticular degeneration 0.036 1 1.75e-3 2.59e-3 ✓ sig.
Colitis inflammatory skin and bowel disease, neonatal, 1 0.029 1 2.14e-3 3.03e-3 ✓ sig.
Colitis thrombocytopenia 6 0.029 1 2.14e-3 3.03e-3 ✓ sig.
Alcoholic hepatitis Chondromalacia 0.077 1 2.60e-3 3.50e-3 ✓ sig.