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 292

6 diseases · 7 shared-gene connections
6 Diseases
99 Unique genes
0.077 Avg. similarity score
Hyperlipoproteinemia Most-connected disease (4 links)
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Disease Searched: Hyperlipoproteinemia 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 ⇵
Hyperlipoproteinemia 4 4 40
Arteriosclerosis 3 3 41
Hypercholesterolemia 3 3 46
hypercholesterolemia, familial, 4 2 2 1
Apolipoprotein c-ii deficiency 1 1 1
Corneal injury 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
APOB 3 / 6 Arteriosclerosis, Hypercholesterolemia, Hyperlipoproteinemia
APOE 3 / 6 Arteriosclerosis, Hypercholesterolemia, Hyperlipoproteinemia
LDLR 3 / 6 Arteriosclerosis, Hypercholesterolemia, Hyperlipoproteinemia
LDLRAP1 3 / 6 Hypercholesterolemia, hypercholesterolemia, familial, 4, Hyperlipoproteinemia
PON1 3 / 6 Arteriosclerosis, Hypercholesterolemia, Hyperlipoproteinemia
ABCA1 2 / 6 Hypercholesterolemia, Hyperlipoproteinemia
ABCG5 2 / 6 Arteriosclerosis, Hypercholesterolemia
ABCG8 2 / 6 Arteriosclerosis, Hyperlipoproteinemia
ADRB2 2 / 6 Hypercholesterolemia, Hyperlipoproteinemia
ALDH3A1 2 / 6 Arteriosclerosis, Corneal injury
APOA2 2 / 6 Hypercholesterolemia, Hyperlipoproteinemia
APOA4 2 / 6 Hypercholesterolemia, Hyperlipoproteinemia
APOC2 2 / 6 Apolipoprotein c-ii deficiency, Hyperlipoproteinemia
APOC3 2 / 6 Hypercholesterolemia, Hyperlipoproteinemia
EPHX2 2 / 6 Hypercholesterolemia, Hyperlipoproteinemia
GHR 2 / 6 Hypercholesterolemia, Hyperlipoproteinemia
HMGCR 2 / 6 Hypercholesterolemia, Hyperlipoproteinemia
ICAM1 2 / 6 Arteriosclerosis, Hypercholesterolemia
LIPC 2 / 6 Hypercholesterolemia, Hyperlipoproteinemia
LPL 2 / 6 Hypercholesterolemia, Hyperlipoproteinemia
NOS3 2 / 6 Arteriosclerosis, Hyperlipoproteinemia
PCSK9 2 / 6 Hypercholesterolemia, Hyperlipoproteinemia
PDE1C 2 / 6 Hypercholesterolemia, Hyperlipoproteinemia
PON2 2 / 6 Hypercholesterolemia, Hyperlipoproteinemia
PPP1R17 2 / 6 Hypercholesterolemia, Hyperlipoproteinemia
VCAM1 2 / 6 Arteriosclerosis, Hypercholesterolemia
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 ⇵
Cholesterol metabolism
APOC2, ABCG5, ABCG8, APOB, APOE, LCAT, LDLR, LDLRAP1, PCSK9, ABCA1, CYP7A1, LPA
 KEGG 19 / 51 45.2× 1.61e-27 3.57e-24 ✓ sig.
Chylomicron remodeling
APOC2, APOB, APOE, APOA5, LPL, APOA1, APOA2, APOC3, GPIHBP1
 Reactome 9 / 9 121× 1.21e-19 7.96e-17 ✓ sig.
Lipid and atherosclerosis
APOB, HSPD1, ICAM1, IL1B, LDLR, MMP1, MMP3, MMP9, NFKBIA, NOS3, TLR4, TNFSF10
 KEGG 21 / 216 11.8× 3.99e-17 1.72e-14 ✓ sig.
Chylomicron assembly
APOC2, APOB, APOE, APOA1, APOA2, APOC3, MTTP
 Reactome 7 / 9 94.4× 7.41e-14 1.86e-11 ✓ sig.
Chylomicron clearance
APOB, APOE, LDLR, LDLRAP1, LIPC
 Reactome 5 / 5 121× 3.44e-11 5.25e-9 ✓ sig.
HDL remodeling
APOC2, APOE, LCAT, APOA1, APOC3, CETP
 Reactome 6 / 10 72.8× 5.50e-11 7.93e-9 ✓ sig.
Interleukin-4 and Interleukin-13 signaling
ALOX5, F13A1, ICAM1, IL10, IL1B, MMP1, MMP2, MMP3, MMP9, PTGS2, VCAM1, CCL2
 Reactome 12 / 108 13.5× 7.23e-11 1.02e-8 ✓ sig.
Retinoid metabolism and transport
APOC2, APOB, APOE, LPL, APOA1, APOA2, APOC3, GPIHBP1
 Reactome 8 / 41 23.7× 1.22e-9 1.27e-7 ✓ sig.
Fluid shear stress and atherosclerosis
GSTA4, ICAM1, IL1B, MMP2, MMP9, NOS3, VCAM1, EDN1, NCF1, NOX1, SELE, CCL2
 KEGG 12 / 141 10.3× 1.65e-9 1.68e-7 ✓ sig.
AGE-RAGE signaling pathway in diabetic complications
ICAM1, IL1B, MMP2, NOS3, VCAM1, COL3A1, EDN1, NOX1, SELE, CCL2
 KEGG 10 / 101 12.0× 9.43e-9 8.02e-7 ✓ sig.
TNF signaling pathway
ICAM1, IL1B, MMP3, MMP9, NFKBIA, PTGS2, VCAM1, EDN1, SELE, CCL2
 KEGG 10 / 119 10.2× 4.62e-8 3.31e-6 ✓ sig.
Bile secretion
ABCG5, ABCG8, LDLR, BAAT, EPHX1, SLC10A1, CYP7A1, HMGCR, ABCB1
 KEGG 9 / 90 12.1× 4.94e-8 3.51e-6 ✓ sig.
Fat digestion and absorption
ABCG5, ABCG8, APOB, ABCA1, APOA1, APOA4, MTTP
 KEGG 7 / 43 19.7× 5.28e-8 3.71e-6 ✓ sig.
Malaria
ICAM1, IL10, IL1B, TLR4, VCAM1, SELE, CCL2
 KEGG 7 / 50 17.0× 1.56e-7 9.70e-6 ✓ sig.
PPAR signaling pathway
MMP1, APOA5, CYP7A1, LPL, APOA1, APOA2, APOC3, PPARA
 KEGG 8 / 76 12.8× 1.90e-7 1.15e-5 ✓ 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 ⇵
cholesterol homeostasis
APOC2, ABCG5, ABCG8, APOB, APOE, LCAT, LDLR, LDLRAP1, PCSK9, APOA5, ABCA1, CES1
 GO:0042632 24 / 112 40.4× 1.42e-32 8.68e-29 ✓ sig.
cholesterol metabolic process
APOB, APOE, LCAT, LDLR, PON1, LDLRAP1, PCSK9, APOA5, ABCA1, CES1, CYP7A1, HMGCR
 GO:0008203 20 / 107 35.3× 6.57e-26 2.27e-22 ✓ sig.
lipoprotein metabolic process
APOB, APOE, LCAT, LDLR, PCSK9, APOA5, ABCA1, APOA1, APOA2, APOA4, APOC3, MTTP
 GO:0042157 13 / 26 94.4× 1.12e-23 3.10e-20 ✓ sig.
reverse cholesterol transport
APOC2, APOE, LCAT, ABCA1, CES1, APOA1, APOA2, APOA4, APOC3, LIPC, CETP
 GO:0043691 11 / 17 122× 6.27e-22 1.30e-18 ✓ sig.
cholesterol efflux
APOC2, ABCG5, ABCG8, APOB, APOE, APOA5, ABCA1, APOA1, APOA2, APOA4, APOC3
 GO:0033344 11 / 31 67.0× 4.04e-18 4.86e-15 ✓ sig.
triglyceride homeostasis
APOC2, ABCG5, ABCG8, APOE, APOA5, LPL, APOA1, APOC3, LIPC, GPIHBP1, CETP
 GO:0070328 11 / 38 54.6× 5.57e-17 5.33e-14 ✓ sig.
cholesterol transport
APOB, LCAT, LDLR, MSR1, LDLRAP1, ABCA1, APOA1, APOA2, LIPC, CETP
 GO:0030301 10 / 28 67.4× 1.32e-16 1.19e-13 ✓ sig.
phospholipid efflux
APOC2, APOE, APOA5, ABCA1, APOA1, APOA2, APOA4, APOC3
 GO:0033700 8 / 13 116× 5.85e-16 4.62e-13 ✓ sig.
high-density lipoprotein particle remodeling
APOE, LCAT, LPL, APOA1, APOA2, APOA4, APOC3, LIPC, CETP
 GO:0034375 9 / 21 80.9× 6.32e-16 4.94e-13 ✓ sig.
very-low-density lipoprotein particle remodeling
APOC2, APOE, LCAT, LPL, APOA4, LIPC, CETP
 GO:0034372 7 / 8 165× 7.52e-16 5.74e-13 ✓ sig.
lipid metabolic process
APOC2, AKR1B1, ALDH3A1, ALOX5, APOB, APOE, LCAT, LDLR, PTGS2, LDLRAP1, PCSK9, BAAT
 GO:0006629 28 / 840 6.3× 2.09e-15 1.49e-12 ✓ sig.
lipid transport
APOC2, ABCG5, ABCG8, APOB, APOE, LDLR, APOA5, SLC10A1, LPA, APOA1, APOA2, APOA4
 GO:0006869 16 / 189 16.0× 3.43e-15 2.37e-12 ✓ sig.
steroid metabolic process
APOB, APOE, LCAT, LDLR, LDLRAP1, PCSK9, ABCA1, CYP7A1, HMGCR, SREBF2, APOA1, CETP
 GO:0008202 12 / 135 16.8× 6.66e-12 2.53e-9 ✓ sig.
lipoprotein biosynthetic process
APOB, APOE, LCAT, ABCA1, APOA1
 GO:0042158 5 / 6 157× 2.25e-11 7.52e-9 ✓ sig.
triglyceride metabolic process
APOE, PCSK9, APOA5, LPL, APOA2, APOC3, MTTP, CETP
 GO:0006641 8 / 39 38.7× 2.50e-11 8.31e-9 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Hypercholesterolemia Hyperlipoproteinemia 0.279 19 1.78e-39 7.34e-38 ✓ sig.
Arteriosclerosis Hypercholesterolemia 0.086 7 2.74e-11 2.90e-10 ✓ sig.
Arteriosclerosis Hyperlipoproteinemia 0.079 6 8.73e-10 7.98e-9 ✓ sig.
Apolipoprotein c-ii deficiency Hyperlipoproteinemia 0.024 1 2.60e-3 3.51e-3 ✓ sig.
hypercholesterolemia, familial, 4 Hyperlipoproteinemia 0.024 1 2.60e-3 3.51e-3 ✓ sig.
Arteriosclerosis Corneal injury 0.024 1 2.66e-3 3.60e-3 ✓ sig.
Hypercholesterolemia hypercholesterolemia, familial, 4 0.021 1 2.99e-3 3.95e-3 ✓ sig.