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 196

8 diseases · 17 shared-gene connections
8 Diseases
35 Unique genes
0.218 Avg. similarity score
Extraskeletal ewing sarcoma Most-connected disease (6 links)
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Disease Searched: Ewing sarcoma 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 ⇵
Extraskeletal ewing sarcoma 6 6 4
Paris-trousseau thrombocytopenia 5 5 1
Peripheral primitive neuroectodermal tumor 5 5 1
Skeletal ewing sarcoma 5 5 5
bleeding disorder, platelet-type, 21 5 5 1
Angiomatoid fibrous histiocytoma 3 3 2
Congenital left-sided heart lesions 3 3 25
Ewing sarcoma 2 2 5

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

Gene ⇵ Member diseases ⇵ Linked diseases
FLI1 6 / 8 bleeding disorder, platelet-type, 21, Congenital left-sided heart lesions, Extraskeletal ewing sarcoma, Paris-trousseau thrombocytopenia and 2 more
EWSR1 4 / 8 Angiomatoid fibrous histiocytoma, Ewing sarcoma, Extraskeletal ewing sarcoma, Skeletal ewing sarcoma
ERG 2 / 8 Extraskeletal ewing sarcoma, Skeletal ewing sarcoma
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 ⇵
cAMP signaling pathway
ATP1A2, ATP1A3, CACNA1C, CRH, CRHR1, CRHR2, DRD2, HTR1A, KCNK2, MAPK1, PDE4D
 KEGG 11 / 226 8.6× 4.91e-8 3.51e-6 ✓ sig.
Hormone signaling
CRH, CRHR1, CRHR2, DRD2, MC4R, OPRK1, ACVR1, INSR, STAT5A
 KEGG 9 / 219 7.3× 3.67e-6 1.47e-4 ✓ sig.
Aldosterone-regulated sodium reabsorption
ATP1A2, ATP1A3, MAPK1, INSR
 KEGG 4 / 38 18.6× 6.00e-5 1.48e-3 ✓ sig.
Synaptic vesicle cycle
SLC17A7, SLC1A3, SLC6A3, SLC6A4, ATP6V0A1
 KEGG 5 / 79 11.2× 8.17e-5 1.90e-3 ✓ sig.
Class B/2 (Secretin family receptors)
CRH, CRHR1, CRHR2
 Reactome 3 / 18 29.4× 1.33e-4 2.83e-3 ✓ sig.
G alpha (s) signalling events
CRH, CRHR1, CRHR2, MC4R, ARRB1, PDE4D
 Reactome 6 / 140 7.6× 1.36e-4 2.88e-3 ✓ sig.
Adrenergic signaling in cardiomyocytes
ATP1A2, ATP1A3, CACNA1C, KCNK2, MAPK1, MYH7
 KEGG 6 / 154 6.9× 2.29e-4 4.36e-3 ✓ sig.
Cushing syndrome
CACNA1C, CRH, CRHR1, CRHR2, KCNK2, MAPK1
 KEGG 6 / 155 6.8× 2.37e-4 4.47e-3 ✓ sig.
cGMP-PKG signaling pathway
ATP1A2, ATP1A3, CACNA1C, MAPK1, MYH7, INSR
 KEGG 6 / 166 6.4× 3.43e-4 5.96e-3 ✓ sig.
GnRH secretion
CACNA1C, MAPK1, ARRB1, KCNN3
 KEGG 4 / 65 10.9× 4.91e-4 7.86e-3 ✓ sig.
Thyroid hormone signaling pathway
ATP1A2, ATP1A3, MAPK1, MYH7, NOTCH1
 KEGG 5 / 122 7.2× 6.23e-4 9.48e-3 ✓ sig.
Dopaminergic synapse
CACNA1C, COMT, DRD2, SLC6A3, ARRB1
 KEGG 5 / 132 6.7× 8.90e-4 1.24e-2 ✓ sig.
Proteoglycans in cancer
ANK3, MAPK1, PTK2, PTPN11, DROSHA, ITGB1
 KEGG 6 / 204 5.2× 1.02e-3 1.37e-2 ✓ sig.
Neuroactive ligand-receptor interaction
CRH, CRHR1, CRHR2, DRD2, HTR1A, MC4R, OPRK1, GABRG2
 KEGG 8 / 370 3.8× 1.11e-3 1.46e-2 ✓ sig.
MAPK1 (ERK2) activation
MAPK1, PTPN11
 Reactome 2 / 9 39.2× 1.11e-3 1.46e-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 ⇵
cAMP/PKA signal transduction
CREB1, ADCYAP1R1, GHRHR
 GO:0141156 3 / 10 160× 7.16e-7 6.38e-5 ✓ sig.
development of primary female sexual characteristics
ADCYAP1R1, DACH1
 GO:0046545 2 / 4 267× 2.04e-5 9.26e-4 ✓ sig.
regulation of DNA-templated transcription
CREB1, EWSR1, DACH1, FLI1, HIVEP3, TFDP2, EGR2, ERG, SMARCA5, ETV1, ETV4
 GO:0006355 11 / 1,454 4.0× 4.42e-5 1.67e-3 ✓ sig.
hormone secretion
CREB1, GHRHR
 GO:0046879 2 / 8 133× 9.48e-5 2.97e-3 ✓ sig.
regulation of transcription by RNA polymerase II
CREB1, DACH1, FLI1, HIVEP3, TFDP2, ZNF438, EGR2, ERG, SMARCA5, ETV1, ETV4
 GO:0006357 11 / 1,602 3.7× 1.07e-4 3.25e-3 ✓ sig.
positive regulation of hormone secretion
CREB1, GHRHR
 GO:0046887 2 / 12 89.0× 2.22e-4 5.54e-3 ✓ sig.
negative regulation of transcription by competitive promoter binding
CREB1, DACH1
 GO:0010944 2 / 13 82.1× 2.62e-4 6.22e-3 ✓ sig.
positive regulation of calcium ion transport into cytosol
ADCYAP1R1, P2RX4
 GO:0010524 2 / 14 76.3× 3.06e-4 6.95e-3 ✓ sig.
positive regulation of DNA-templated transcription
CREB1, AFAP1L2, FLI1, HIVEP3, EGR2, SMARCA5, ETV1
 GO:0045893 7 / 778 4.8× 5.11e-4 9.88e-3 ✓ sig.
cellular response to zinc ion
CREB1, P2RX4
 GO:0071294 2 / 25 42.7× 9.95e-4 1.53e-2 ✓ sig.
positive regulation of transcription by RNA polymerase II
CREB1, FLI1, TFDP2, EGR2, ERG, SMARCA5, ETV1, ETV4
 GO:0045944 8 / 1,208 3.5× 1.46e-3 1.92e-2 ✓ sig.
neuronal action potential
GJD2, KCNMB2
 GO:0019228 2 / 34 31.4× 1.84e-3 2.22e-2 ✓ sig.
positive regulation of multicellular organism growth
CREB1, GHRHR
 GO:0040018 2 / 34 31.4× 1.84e-3 2.22e-2 ✓ sig.
negative regulation of response to reactive oxygen species
ADCYAP1R1
 GO:1901032 1 / 1 534× 1.87e-3 2.24e-2 ✓ sig.
rhombomere 3 structural organization
EGR2
 GO:0021659 1 / 1 534× 1.87e-3 2.24e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Extraskeletal ewing sarcoma Skeletal ewing sarcoma 0.429 3 6.57e-11 6.69e-10 ✓ sig.
bleeding disorder, platelet-type, 21 Paris-trousseau thrombocytopenia 0.500 1 6.49e-5 2.32e-4 ✓ sig.
bleeding disorder, platelet-type, 21 Peripheral primitive neuroectodermal tumor 0.500 1 6.49e-5 2.32e-4 ✓ sig.
Paris-trousseau thrombocytopenia Peripheral primitive neuroectodermal tumor 0.500 1 6.49e-5 2.32e-4 ✓ sig.
bleeding disorder, platelet-type, 21 Extraskeletal ewing sarcoma 0.200 1 2.60e-4 6.48e-4 ✓ sig.
Extraskeletal ewing sarcoma Peripheral primitive neuroectodermal tumor 0.200 1 2.60e-4 6.48e-4 ✓ sig.
Extraskeletal ewing sarcoma Paris-trousseau thrombocytopenia 0.200 1 2.60e-4 6.48e-4 ✓ sig.
Peripheral primitive neuroectodermal tumor Skeletal ewing sarcoma 0.167 1 3.25e-4 7.68e-4 ✓ sig.
bleeding disorder, platelet-type, 21 Skeletal ewing sarcoma 0.167 1 3.25e-4 7.68e-4 ✓ sig.
Paris-trousseau thrombocytopenia Skeletal ewing sarcoma 0.167 1 3.25e-4 7.68e-4 ✓ sig.
Angiomatoid fibrous histiocytoma Extraskeletal ewing sarcoma 0.167 1 5.19e-4 1.06e-3 ✓ sig.
Angiomatoid fibrous histiocytoma Ewing sarcoma 0.143 1 6.49e-4 1.24e-3 ✓ sig.
Angiomatoid fibrous histiocytoma Skeletal ewing sarcoma 0.143 1 6.49e-4 1.24e-3 ✓ sig.
Ewing sarcoma Extraskeletal ewing sarcoma 0.111 1 1.30e-3 2.06e-3 ✓ sig.
bleeding disorder, platelet-type, 21 Congenital left-sided heart lesions 0.038 1 1.62e-3 2.46e-3 ✓ sig.
Congenital left-sided heart lesions Peripheral primitive neuroectodermal tumor 0.038 1 1.62e-3 2.46e-3 ✓ sig.
Congenital left-sided heart lesions Paris-trousseau thrombocytopenia 0.038 1 1.62e-3 2.46e-3 ✓ sig.