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 368

5 diseases · 7 shared-gene connections
5 Diseases
74 Unique genes
0.176 Avg. similarity score
Liver failure Most-connected disease (4 links)
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Disease Searched: Dihydropteridine reductase deficiency 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 ⇵
Liver failure 4 4 52
Diabetic angiopathies 3 3 28
Diabetic peripheral angiopathy 3 3 28
autoimmune lymphoproliferative syndrome type 1 3 3 1
Dihydropteridine reductase deficiency 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
FASLG 4 / 5 autoimmune lymphoproliferative syndrome type 1, Diabetic angiopathies, Diabetic peripheral angiopathy, Liver failure
ALB 3 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy, Liver failure
ASS1 3 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy, Liver failure
IL1RN 3 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy, Liver failure
TNF 3 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy, Liver failure
VEGFA 3 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy, Liver failure
ADCY3 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
ADCY8 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
AGER 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
CASP3 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
CREM 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
CXCL12 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
EPO 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
GCH1 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
HLA-DRB1 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
HMOX1 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
HP 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
IGFBP1 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
MTHFR 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
NOS3 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
PLAT 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
PON1 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
QDPR 2 / 5 Dihydropteridine reductase deficiency, Liver failure
RELA 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
SERPINE1 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
SERPINF1 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
SOD2 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
THBS1 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
THBS2 2 / 5 Diabetic angiopathies, Diabetic peripheral angiopathy
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 ⇵
Alcoholic liver disease
CASP3, FASLG, RELA, TNF, ACADM, ADH1A, ADH1B, FABP1, FAS, MAPK8
 KEGG 10 / 144 11.3× 1.67e-8 1.44e-6 ✓ sig.
AGE-RAGE signaling pathway in diabetic complications
AGER, CASP3, NOS3, RELA, SERPINE1, TNF, VEGFA, MAPK8
 KEGG 8 / 101 12.9× 1.80e-7 1.17e-5 ✓ sig.
HIF-1 signaling pathway
EPO, HMOX1, NOS3, RELA, SERPINE1, VEGFA, INS, LDHA
 KEGG 8 / 110 11.8× 3.50e-7 2.09e-5 ✓ sig.
Fluid shear stress and atherosclerosis
ASS1, HMOX1, NOS3, PLAT, RELA, TNF, VEGFA, MAPK8
 KEGG 8 / 141 9.2× 2.32e-6 1.08e-4 ✓ sig.
Non-alcoholic fatty liver disease
CASP3, FASLG, RELA, TNF, COX3, FAS, INS, MAPK8
 KEGG 8 / 157 8.3× 5.18e-6 2.08e-4 ✓ sig.
Lipid and atherosclerosis
AGER, CASP3, FASLG, NOS3, RELA, SOD2, TNF, FAS, MAPK8
 KEGG 9 / 216 6.8× 6.69e-6 2.56e-4 ✓ sig.
Type I diabetes mellitus
FASLG, HLA-DRB1, TNF, FAS, INS
 KEGG 5 / 44 18.4× 6.97e-6 2.65e-4 ✓ sig.
Human cytomegalovirus infection
ADCY3, ADCY8, CASP3, CXCL12, FASLG, RELA, TNF, VEGFA, FAS
 KEGG 9 / 226 6.5× 9.64e-6 3.44e-4 ✓ sig.
Malaria
THBS1, THBS2, TNF, CSF3, HGF
 KEGG 5 / 50 16.2× 1.32e-5 4.46e-4 ✓ sig.
Pathways in cancer
ADCY3, ADCY8, CASP3, CXCL12, EPO, FASLG, HMOX1, RELA, VEGFA, F2, FAS, HGF
 KEGG 13 / 533 4.0× 1.95e-5 6.16e-4 ✓ sig.
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes
IGFBP1, SOD2, INS
 Reactome 3 / 10 48.7× 2.61e-5 7.88e-4 ✓ sig.
Chagas disease
FASLG, RELA, SERPINE1, TNF, FAS, MAPK8
 KEGG 6 / 103 9.5× 3.97e-5 1.11e-3 ✓ sig.
Interleukin-4 and Interleukin-13 signaling
FASLG, HMOX1, TNF, VEGFA, HGF, POMC
 Reactome 6 / 108 9.0× 5.19e-5 1.38e-3 ✓ sig.
Glycolysis / Gluconeogenesis
ADH1A, ADH1B, FBP1, FBP2, LDHA
 KEGG 5 / 67 12.1× 5.56e-5 1.46e-3 ✓ sig.
PI3K-Akt signaling pathway
EPO, FASLG, NOS3, RELA, THBS1, THBS2, VEGFA, CSF3, HGF, INS
 KEGG 10 / 361 4.5× 6.89e-5 1.73e-3 ✓ 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 hypoxia
AGER, CASP3, CXCL12, EPO, MTHFR, PLAT, SOD2, THBS1, TNF, VEGFA, F7
 GO:0001666 11 / 176 15.8× 9.45e-11 2.76e-8 ✓ sig.
acute-phase response
ASS1, EPO, HP, IL1RN, F2, ORM1, INS
 GO:0006953 7 / 37 47.8× 1.07e-10 3.10e-8 ✓ sig.
response to lipopolysaccharide
ASS1, CASP3, EPO, FASLG, GCH1, NOS3, RELA, SOD2, TNF
 GO:0032496 9 / 161 14.1× 1.43e-8 2.33e-6 ✓ sig.
response to nutrient levels
ALB, SOD2, TNF, ATG7, F7, FBP1, GC
 GO:0031667 7 / 79 22.4× 2.64e-8 3.97e-6 ✓ sig.
extrinsic apoptotic signaling pathway
FASLG, TNF, FAS, INHBA, KRT18, KRT8
 GO:0097191 6 / 57 26.6× 9.70e-8 1.20e-5 ✓ sig.
negative regulation of fibrinolysis
PLAT, SERPINE1, THBS1, F2
 GO:0051918 4 / 12 84.2× 1.09e-7 1.33e-5 ✓ sig.
response to hydrogen peroxide
CASP3, HMOX1, HP, RELA, SOD2
 GO:0042542 5 / 39 32.4× 4.40e-7 4.32e-5 ✓ sig.
liver development
ASS1, RELA, SOD2, ACADM, GFER, HGF
 GO:0001889 6 / 87 17.4× 1.23e-6 1.00e-4 ✓ sig.
positive regulation of ERK1 and ERK2 cascade
AGER, EPO, HLA-DRB1, TNF, VEGFA, CD74, GPNMB, INHBA
 GO:0070374 8 / 201 10.1× 1.28e-6 1.04e-4 ✓ sig.
vasodilation
NOS3, SOD2, TNF, VEGFA, INS
 GO:0042311 5 / 50 25.3× 1.57e-6 1.23e-4 ✓ sig.
response to amino acid
ASS1, CASP3, MTHFR, RELA
 GO:0043200 4 / 22 45.9× 1.57e-6 1.23e-4 ✓ sig.
negative regulation of plasminogen activation
PLAT, SERPINE1, THBS1
 GO:0010757 3 / 7 108× 2.06e-6 1.52e-4 ✓ sig.
positive regulation of cell migration
AGER, CXCL12, SOD2, THBS1, VEGFA, F7, GPNMB, HGF, INS
 GO:0030335 9 / 292 7.8× 2.23e-6 1.63e-4 ✓ sig.
positive regulation of canonical NF-kappaB signal transduction
FASLG, HLA-DRB1, HMOX1, RELA, TNF, VEGFA, CD74, INS
 GO:0043123 8 / 232 8.7× 3.73e-6 2.44e-4 ✓ sig.
tumor necrosis factor-mediated signaling pathway
RELA, TNF, FAS, KRT18, KRT8
 GO:0033209 5 / 60 21.0× 3.91e-6 2.54e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Diabetic angiopathies Diabetic peripheral angiopathy 0.966 28 1.76e-88 1.55e-86 ✓ sig.
Diabetic angiopathies Liver failure 0.080 6 3.92e-10 3.69e-9 ✓ sig.
Diabetic peripheral angiopathy Liver failure 0.080 6 3.92e-10 3.69e-9 ✓ sig.
autoimmune lymphoproliferative syndrome type 1 Diabetic angiopathies 0.034 1 1.82e-3 2.68e-3 ✓ sig.
autoimmune lymphoproliferative syndrome type 1 Diabetic peripheral angiopathy 0.034 1 1.82e-3 2.68e-3 ✓ sig.
autoimmune lymphoproliferative syndrome type 1 Liver failure 0.019 1 3.38e-3 4.37e-3 ✓ sig.
Dihydropteridine reductase deficiency Liver failure 0.019 1 3.38e-3 4.37e-3 ✓ sig.