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 185

8 diseases · 21 shared-gene connections
8 Diseases
5 Unique genes
0.387 Avg. similarity score
Dystransthyretinemic euthyroidal hyperthyroxinemia Most-connected disease (6 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 ⇵
Dystransthyretinemic euthyroidal hyperthyroxinemia 6 6 1
Hyperthyroxinemia 6 6 3
Senile systemic amyloidosis 6 6 1
Transthyretin amyloid cardiomyopathy 6 6 1
Wild-type transthyretin-related amyloidosis 6 6 1
obsolete hereditary ATTR amyloidosis 6 6 1
Amyloid polyneuropathy 5 5 2
Thyroid hormone metabolism disorder 1 1 2

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

Gene ⇵ Member diseases ⇵ Linked diseases
TTR 7 / 8 Amyloid polyneuropathy, Dystransthyretinemic euthyroidal hyperthyroxinemia, Hyperthyroxinemia, obsolete hereditary ATTR amyloidosis and 3 more
DIO1 2 / 8 Hyperthyroxinemia, Thyroid hormone metabolism disorder
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 ⇵
HDL remodeling
APOA1, ALB
 Reactome 2 / 10 480× 6.23e-6 2.26e-4 ✓ sig.
Scavenging of heme from plasma
APOA1, ALB
 Reactome 2 / 13 370× 1.08e-5 3.58e-4 ✓ sig.
Retinoid metabolism and transport
TTR, APOA1
 Reactome 2 / 41 117× 1.13e-4 2.48e-3 ✓ sig.
Thyroid hormone synthesis
TTR, ALB
 KEGG 2 / 75 64.1× 3.80e-4 6.45e-3 ✓ sig.
Post-translational protein phosphorylation
APOA1, ALB
 Reactome 2 / 108 44.5× 7.87e-4 1.14e-2 ✓ sig.
Amyloid fiber formation
TTR, APOA1
 Reactome 2 / 109 44.1× 8.02e-4 1.15e-2 ✓ sig.
Defective ABCA1 causes Tangier disease
APOA1
 Reactome 1 / 2 1,201× 8.33e-4 1.18e-2 ✓ sig.
Platelet degranulation
APOA1, ALB
 Reactome 2 / 123 39.1× 1.02e-3 1.38e-2 ✓ sig.
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
APOA1, ALB
 Reactome 2 / 125 38.4× 1.05e-3 1.41e-2 ✓ sig.
Regulation of thyroid hormone activity
DIO1
 Reactome 1 / 3 801× 1.25e-3 1.60e-2 ✓ sig.
HDL clearance
APOA1
 Reactome 1 / 5 480× 2.08e-3 2.35e-2 ✓ sig.
Scavenging by Class B Receptors
APOA1
 Reactome 1 / 5 480× 2.08e-3 2.35e-2 ✓ sig.
HDL assembly
APOA1
 Reactome 1 / 8 300× 3.33e-3 3.31e-2 ✓ sig.
Chylomicron remodeling
APOA1
 Reactome 1 / 9 267× 3.74e-3 3.59e-2 ✓ sig.
Chylomicron assembly
APOA1
 Reactome 1 / 9 267× 3.74e-3 3.59e-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 ⇵
protein oxidation
APOA1
 GO:0018158 1 / 3 1,246× 8.03e-4 1.30e-2 ✓ sig.
peptidyl-methionine modification
APOA1
 GO:0018206 1 / 3 1,246× 8.03e-4 1.30e-2 ✓ sig.
thyroid hormone catabolic process
DIO1
 GO:0042404 1 / 3 1,246× 8.03e-4 1.30e-2 ✓ sig.
positive regulation of phospholipid efflux
APOA1
 GO:1902995 1 / 4 934× 1.07e-3 1.57e-2 ✓ sig.
regulation of intestinal cholesterol absorption
APOA1
 GO:0030300 1 / 4 934× 1.07e-3 1.57e-2 ✓ sig.
negative regulation of glomerular filtration
TTR
 GO:0003105 1 / 4 934× 1.07e-3 1.57e-2 ✓ sig.
cellular response to calcium ion starvation
ALB
 GO:0072732 1 / 4 934× 1.07e-3 1.57e-2 ✓ sig.
acylglycerol homeostasis
APOA1
 GO:0055090 1 / 5 747× 1.34e-3 1.79e-2 ✓ sig.
cellular response to lipoprotein particle stimulus
APOA1
 GO:0071402 1 / 5 747× 1.34e-3 1.79e-2 ✓ sig.
lipoprotein biosynthetic process
APOA1
 GO:0042158 1 / 6 623× 1.60e-3 1.98e-2 ✓ sig.
negative regulation of very-low-density lipoprotein particle remodeling
APOA1
 GO:0010903 1 / 6 623× 1.60e-3 1.98e-2 ✓ sig.
cholesterol import
APOA1
 GO:0070508 1 / 6 623× 1.60e-3 1.98e-2 ✓ sig.
purine nucleobase metabolic process
TTR
 GO:0006144 1 / 7 534× 1.87e-3 2.19e-2 ✓ sig.
positive regulation of cholesterol metabolic process
APOA1
 GO:0090205 1 / 7 534× 1.87e-3 2.19e-2 ✓ sig.
negative regulation of cytokine production involved in immune response
APOA1
 GO:0002719 1 / 7 534× 1.87e-3 2.19e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Transthyretin amyloid cardiomyopathy Wild-type transthyretin-related amyloidosis 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Dystransthyretinemic euthyroidal hyperthyroxinemia Senile systemic amyloidosis 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Dystransthyretinemic euthyroidal hyperthyroxinemia Transthyretin amyloid cardiomyopathy 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Dystransthyretinemic euthyroidal hyperthyroxinemia Wild-type transthyretin-related amyloidosis 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Dystransthyretinemic euthyroidal hyperthyroxinemia obsolete hereditary ATTR amyloidosis 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Senile systemic amyloidosis Wild-type transthyretin-related amyloidosis 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Senile systemic amyloidosis Transthyretin amyloid cardiomyopathy 0.500 1 6.49e-5 2.34e-4 ✓ sig.
obsolete hereditary ATTR amyloidosis Wild-type transthyretin-related amyloidosis 0.500 1 6.49e-5 2.34e-4 ✓ sig.
obsolete hereditary ATTR amyloidosis Transthyretin amyloid cardiomyopathy 0.500 1 6.49e-5 2.34e-4 ✓ sig.
obsolete hereditary ATTR amyloidosis Senile systemic amyloidosis 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Amyloid polyneuropathy Senile systemic amyloidosis 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Amyloid polyneuropathy Wild-type transthyretin-related amyloidosis 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Amyloid polyneuropathy obsolete hereditary ATTR amyloidosis 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Amyloid polyneuropathy Transthyretin amyloid cardiomyopathy 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Amyloid polyneuropathy Dystransthyretinemic euthyroidal hyperthyroxinemia 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Hyperthyroxinemia obsolete hereditary ATTR amyloidosis 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Hyperthyroxinemia Wild-type transthyretin-related amyloidosis 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Hyperthyroxinemia Transthyretin amyloid cardiomyopathy 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Hyperthyroxinemia Senile systemic amyloidosis 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Dystransthyretinemic euthyroidal hyperthyroxinemia Hyperthyroxinemia 0.250 1 1.95e-4 5.28e-4 ✓ sig.
Hyperthyroxinemia Thyroid hormone metabolism disorder 0.200 1 3.90e-4 8.52e-4 ✓ sig.