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 221

7 diseases · 13 shared-gene connections
7 Diseases
19 Unique genes
0.327 Avg. similarity score
Visceral amyloidosis Most-connected disease (6 links)
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Disease Searched: hypoproteinemia, hypercatabolic 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 ⇵
Visceral amyloidosis 6 6 4
Beta2-microglobulinic amyloidosis 4 4 1
Hypergammaglobulinemia 4 4 1
amyloidosis, hereditary systemic 6 4 4 1
hypoproteinemia, hypercatabolic 4 4 1
Alys amyloidosis 2 2 1
Amyloidosis 2 2 19

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

Gene ⇵ Member diseases ⇵ Linked diseases
B2M 6 / 7 Amyloidosis, amyloidosis, hereditary systemic 6, Beta2-microglobulinic amyloidosis, Hypergammaglobulinemia and 2 more
LYZ 3 / 7 Alys amyloidosis, Amyloidosis, Visceral amyloidosis
APOA1 2 / 7 Amyloidosis, Visceral amyloidosis
FGA 2 / 7 Amyloidosis, Visceral amyloidosis
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 ⇵
Amyloid fiber formation
FGA, LYZ, APCS, APP, GSN, TTR, APOA1, B2M
 Reactome 8 / 109 46.4× 2.47e-12 4.67e-10 ✓ sig.
Post-translational protein phosphorylation
FGA, APOE, APP, APOA1
 Reactome 4 / 108 23.4× 2.16e-5 6.50e-4 ✓ sig.
Retinoid metabolism and transport
APOE, TTR, APOA1
 Reactome 3 / 41 46.3× 3.45e-5 9.52e-4 ✓ sig.
Platelet degranulation
FGA, APP, SERPINE1, APOA1
 Reactome 4 / 123 20.6× 3.60e-5 9.87e-4 ✓ sig.
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
FGA, APOE, APP, APOA1
 Reactome 4 / 125 20.2× 3.84e-5 1.04e-3 ✓ sig.
Neutrophil degranulation
LYZ, DSP, GSN, PSEN1, TTR, B2M
 Reactome 6 / 480 7.9× 6.87e-5 1.67e-3 ✓ sig.
Chylomicron remodeling
APOE, APOA1
 Reactome 2 / 9 140× 8.48e-5 1.98e-3 ✓ sig.
Chylomicron assembly
APOE, APOA1
 Reactome 2 / 9 140× 8.48e-5 1.98e-3 ✓ sig.
HDL remodeling
APOE, APOA1
 Reactome 2 / 10 126× 1.06e-4 2.38e-3 ✓ sig.
Scavenging by Class A Receptors
APOE, APOA1
 Reactome 2 / 11 115× 1.29e-4 2.79e-3 ✓ sig.
IL-6-type cytokine receptor ligand interactions
OSMR, IL31RA
 Reactome 2 / 17 74.4× 3.18e-4 5.70e-3 ✓ sig.
Nuclear signaling by ERBB4
APOE, PSEN1
 Reactome 2 / 24 52.7× 6.41e-4 9.88e-3 ✓ sig.
Cholesterol metabolism
APOE, APOA1
 KEGG 2 / 51 24.8× 2.89e-3 3.04e-2 ✓ sig.
ECM proteoglycans
APP, SERPINE1
 Reactome 2 / 51 24.8× 2.89e-3 3.04e-2 ✓ sig.
Defective ABCA1 causes Tangier disease
APOA1
 Reactome 1 / 2 316× 3.16e-3 3.24e-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 ⇵
positive regulation of amyloid fibril formation
APOE, APP, PSEN1
 GO:1905908 3 / 5 590× 8.90e-9 1.51e-6 ✓ sig.
amyloid precursor protein metabolic process
ACHE, APOE, PSEN1
 GO:0042982 3 / 12 246× 1.95e-7 2.15e-5 ✓ sig.
cellular response to amyloid-beta
APOE, APP, PSEN1, APOA1
 GO:1904646 4 / 53 74.2× 2.17e-7 2.35e-5 ✓ sig.
lipoprotein metabolic process
APOE, APP, APOA1
 GO:0042157 3 / 26 113× 2.28e-6 1.63e-4 ✓ sig.
regulation of amyloid-beta clearance
APOE, APP
 GO:1900221 2 / 3 656× 2.94e-6 2.00e-4 ✓ sig.
regulation of amyloid fibril formation
APOE, APP
 GO:1905906 2 / 3 656× 2.94e-6 2.00e-4 ✓ sig.
amyloid fibril formation
APP, GSN, B2M
 GO:1990000 3 / 29 102× 3.20e-6 2.15e-4 ✓ sig.
defense response to Gram-negative bacterium
LYZ, APP, SERPINE1, B2M
 GO:0050829 4 / 106 37.1× 3.55e-6 2.33e-4 ✓ sig.
positive regulation of phospholipid efflux
APOE, APOA1
 GO:1902995 2 / 4 492× 5.87e-6 3.48e-4 ✓ sig.
astrocyte activation involved in immune response
APP, PSEN1
 GO:0002265 2 / 4 492× 5.87e-6 3.48e-4 ✓ sig.
acylglycerol homeostasis
APOE, APOA1
 GO:0055090 2 / 5 393× 9.78e-6 5.21e-4 ✓ sig.
cellular response to lipoprotein particle stimulus
APOE, APOA1
 GO:0071402 2 / 5 393× 9.78e-6 5.21e-4 ✓ sig.
lipoprotein biosynthetic process
APOE, APOA1
 GO:0042158 2 / 6 328× 1.47e-5 7.15e-4 ✓ sig.
positive regulation of coagulation
PSEN1, SERPINE1
 GO:0050820 2 / 6 328× 1.47e-5 7.15e-4 ✓ sig.
positive regulation of cholesterol metabolic process
APOE, APOA1
 GO:0090205 2 / 7 281× 2.05e-5 9.30e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Amyloidosis Visceral amyloidosis 0.200 4 1.66e-12 1.94e-11 ✓ sig.
amyloidosis, hereditary systemic 6 Beta2-microglobulinic amyloidosis 0.500 1 6.49e-5 2.32e-4 ✓ sig.
amyloidosis, hereditary systemic 6 Hypergammaglobulinemia 0.500 1 6.49e-5 2.32e-4 ✓ sig.
amyloidosis, hereditary systemic 6 hypoproteinemia, hypercatabolic 0.500 1 6.49e-5 2.32e-4 ✓ sig.
Beta2-microglobulinic amyloidosis Hypergammaglobulinemia 0.500 1 6.49e-5 2.32e-4 ✓ sig.
Beta2-microglobulinic amyloidosis hypoproteinemia, hypercatabolic 0.500 1 6.49e-5 2.32e-4 ✓ sig.
Hypergammaglobulinemia hypoproteinemia, hypercatabolic 0.500 1 6.49e-5 2.32e-4 ✓ sig.
Alys amyloidosis Visceral amyloidosis 0.200 1 2.60e-4 6.48e-4 ✓ sig.
amyloidosis, hereditary systemic 6 Visceral amyloidosis 0.200 1 2.60e-4 6.48e-4 ✓ sig.
Beta2-microglobulinic amyloidosis Visceral amyloidosis 0.200 1 2.60e-4 6.48e-4 ✓ sig.
Hypergammaglobulinemia Visceral amyloidosis 0.200 1 2.60e-4 6.48e-4 ✓ sig.
hypoproteinemia, hypercatabolic Visceral amyloidosis 0.200 1 2.60e-4 6.48e-4 ✓ sig.
Alys amyloidosis Amyloidosis 0.050 1 1.23e-3 1.98e-3 ✓ sig.