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 382

5 diseases · 6 shared-gene connections
5 Diseases
15 Unique genes
0.181 Avg. similarity score
Charcot-Marie-Tooth disease type 1A Most-connected disease (3 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 ⇵
Charcot-Marie-Tooth disease type 1A 3 3 1
Demyelinating diseases 3 3 11
Hereditary neuropathy with liability to pressure palsies 3 3 1
Paresthesia 2 2 5
Merkel cell carcinoma 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
PMP22 4 / 5 Charcot-Marie-Tooth disease type 1A, Demyelinating diseases, Hereditary neuropathy with liability to pressure palsies, Paresthesia
MYC 2 / 5 Demyelinating diseases, Merkel cell carcinoma
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 ⇵
Longevity regulating pathway
IGF1, SIRT1, TP53, INS
 KEGG 4 / 90 35.6× 3.78e-6 1.51e-4 ✓ sig.
Longevity regulating pathway - multiple species
IGF1, SIRT1, INS
 KEGG 3 / 62 38.7× 5.70e-5 1.42e-3 ✓ sig.
Prostate cancer
IGF1, TP53, INS
 KEGG 3 / 98 24.5× 2.23e-4 4.27e-3 ✓ sig.
Synthesis, secretion, and deacylation of Ghrelin
IGF1, INS
 Reactome 2 / 19 84.3× 2.46e-4 4.59e-3 ✓ sig.
EGR2 and SOX10-mediated initiation of Schwann cell myelination
MBP, PMP22
 Reactome 2 / 20 80.1× 2.73e-4 4.98e-3 ✓ sig.
MAPK signaling pathway
MYC, IGF1, TP53, INS
 KEGG 4 / 299 10.7× 4.14e-4 6.88e-3 ✓ sig.
AMPK signaling pathway
IGF1, SIRT1, INS
 KEGG 3 / 122 19.7× 4.26e-4 7.03e-3 ✓ sig.
FoxO signaling pathway
IGF1, SIRT1, INS
 KEGG 3 / 133 18.1× 5.48e-4 8.54e-3 ✓ sig.
Breast cancer
MYC, IGF1, TP53
 KEGG 3 / 148 16.2× 7.48e-4 1.09e-2 ✓ sig.
PI3K-Akt signaling pathway
MYC, IGF1, TP53, INS
 KEGG 4 / 361 8.9× 8.42e-4 1.19e-2 ✓ sig.
Cellular senescence
MYC, SIRT1, TP53
 KEGG 3 / 157 15.3× 8.88e-4 1.24e-2 ✓ sig.
Thyroid cancer
MYC, TP53
 KEGG 2 / 37 43.3× 9.46e-4 1.30e-2 ✓ sig.
Aldosterone-regulated sodium reabsorption
IGF1, INS
 KEGG 2 / 38 42.1× 9.97e-4 1.35e-2 ✓ sig.
Bladder cancer
MYC, TP53
 KEGG 2 / 41 39.1× 1.16e-3 1.52e-2 ✓ sig.
Wnt signaling pathway
MYC, SIRT1, TP53
 KEGG 3 / 174 13.8× 1.20e-3 1.55e-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 ⇵
central nervous system development
KLK6, MBP, MOG, TP53, FKRP
 GO:0007417 5 / 158 39.4× 1.14e-7 1.34e-5 ✓ sig.
myelination
KLK6, MBP, PMP22, QKI
 GO:0042552 4 / 73 68.3× 2.83e-7 2.91e-5 ✓ sig.
axon ensheathment
MBP, QKI
 GO:0008366 2 / 7 356× 1.26e-5 6.25e-4 ✓ sig.
signal transduction by p53 class mediator
SIRT1, TP53
 GO:0072331 2 / 9 277× 2.16e-5 9.54e-4 ✓ sig.
positive regulation of gene expression
MYC, IGF1, QKI, TP53, INS
 GO:0010628 5 / 504 12.4× 3.36e-5 1.33e-3 ✓ sig.
circadian rhythm
IGF1, SIRT1, TP53
 GO:0007623 3 / 82 45.6× 3.57e-5 1.40e-3 ✓ sig.
negative regulation of apoptotic process
MYC, IGF1, SIRT1, TP53, CAPN3
 GO:0043066 5 / 524 11.9× 4.05e-5 1.54e-3 ✓ sig.
myotube differentiation
MYC, IGF1
 GO:0014902 2 / 16 156× 7.17e-5 2.36e-3 ✓ sig.
positive regulation of glycogen biosynthetic process
IGF1, INS
 GO:0045725 2 / 17 147× 8.12e-5 2.59e-3 ✓ sig.
negative regulation of androgen receptor signaling pathway
IGF1, SIRT1
 GO:0060766 2 / 17 147× 8.12e-5 2.59e-3 ✓ sig.
fatty acid homeostasis
SIRT1, INS
 GO:0055089 2 / 18 138× 9.13e-5 2.83e-3 ✓ sig.
negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
SIRT1, INS
 GO:1902176 2 / 18 138× 9.13e-5 2.83e-3 ✓ sig.
muscle organ development
IGF1, SIRT1, CAPN3
 GO:0007517 3 / 114 32.8× 9.54e-5 2.92e-3 ✓ sig.
muscle structure development
CAPN3, FKRP
 GO:0061061 2 / 19 131× 1.02e-4 3.07e-3 ✓ sig.
positive regulation of cellular senescence
SIRT1, TP53
 GO:2000774 2 / 20 125× 1.13e-4 3.32e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Charcot-Marie-Tooth disease type 1A Hereditary neuropathy with liability to pressure palsies 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Charcot-Marie-Tooth disease type 1A Paresthesia 0.167 1 3.25e-4 7.58e-4 ✓ sig.
Hereditary neuropathy with liability to pressure palsies Paresthesia 0.167 1 3.25e-4 7.58e-4 ✓ sig.
Charcot-Marie-Tooth disease type 1A Demyelinating diseases 0.083 1 7.14e-4 1.31e-3 ✓ sig.
Demyelinating diseases Hereditary neuropathy with liability to pressure palsies 0.083 1 7.14e-4 1.31e-3 ✓ sig.
Demyelinating diseases Merkel cell carcinoma 0.083 1 7.14e-4 1.31e-3 ✓ sig.