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 283

6 diseases · 8 shared-gene connections
6 Diseases
105 Unique genes
0.117 Avg. similarity score
Differentiated thyroid carcinoma Most-connected disease (4 links)
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Disease Searched: Thyroid carcinoma 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 ⇵
Differentiated thyroid carcinoma 4 4 49
Thyroid cancer 3 3 34
Thyroid carcinoma 3 3 9
Toxic nodular goiter 3 3 17
Hurthle cell thyroid cancer 2 2 1
Multinodular goiter 1 1 28

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

Gene ⇵ Member diseases ⇵ Linked diseases
MBIP 4 / 6 Differentiated thyroid carcinoma, Multinodular goiter, Thyroid cancer, Toxic nodular goiter
NRG1 4 / 6 Differentiated thyroid carcinoma, Thyroid cancer, Thyroid carcinoma, Toxic nodular goiter
NDUFA13 3 / 6 Differentiated thyroid carcinoma, Hurthle cell thyroid cancer, Thyroid carcinoma
NFIA 3 / 6 Differentiated thyroid carcinoma, Multinodular goiter, Toxic nodular goiter
PCNX2 3 / 6 Differentiated thyroid carcinoma, Thyroid cancer, Thyroid carcinoma
SLK 3 / 6 Differentiated thyroid carcinoma, Thyroid cancer, Toxic nodular goiter
STN1 3 / 6 Differentiated thyroid carcinoma, Thyroid cancer, Toxic nodular goiter
TERT 3 / 6 Differentiated thyroid carcinoma, Thyroid cancer, Toxic nodular goiter
TG 3 / 6 Multinodular goiter, Thyroid cancer, Toxic nodular goiter
TRMO 3 / 6 Differentiated thyroid carcinoma, Thyroid cancer, Thyroid carcinoma
BCAS3 2 / 6 Multinodular goiter, Toxic nodular goiter
FAM227B 2 / 6 Multinodular goiter, Toxic nodular goiter
FGF7 2 / 6 Multinodular goiter, Toxic nodular goiter
FOXE1 2 / 6 Differentiated thyroid carcinoma, Thyroid cancer
INSR 2 / 6 Multinodular goiter, Toxic nodular goiter
ITPK1 2 / 6 Multinodular goiter, Toxic nodular goiter
MICOS10 2 / 6 Multinodular goiter, Toxic nodular goiter
PRDM11 2 / 6 Multinodular goiter, Toxic nodular goiter
SEPTIN11 2 / 6 Differentiated thyroid carcinoma, Thyroid carcinoma
SOWAHB 2 / 6 Differentiated thyroid carcinoma, Thyroid carcinoma
VAV3 2 / 6 Differentiated thyroid carcinoma, Thyroid 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 ⇵
Thyroid cancer
BRAF, CCDC6, HRAS, KRAS, NCOA4, NRAS, NTRK1, PAX8, PPARG, RET, TFG, TPR
 KEGG 12 / 37 37.1× 1.62e-16 6.45e-14 ✓ sig.
FoxO signaling pathway
BRAF, GRM1, HRAS, KRAS, NRAS, PRKAG2, INSR, SKP2, SMAD3, TGFB2, SOD2
 KEGG 11 / 133 9.5× 2.08e-8 1.57e-6 ✓ sig.
Pathways in cancer
ALK, BRAF, CCDC6, HRAS, KRAS, LPAR4, NCOA4, NRAS, NTRK1, PAX8, PPARG, RET
 KEGG 19 / 533 4.1× 1.50e-7 9.00e-6 ✓ sig.
RAS GTPase cycle mutants
HRAS, KRAS, NRAS
 Reactome 3 / 3 114× 6.49e-7 3.21e-5 ✓ sig.
Chronic myeloid leukemia
BRAF, HRAS, KRAS, NRAS, GAB2, SMAD3, TGFB2
 KEGG 7 / 77 10.4× 4.65e-6 1.73e-4 ✓ sig.
SHC1 events in ERBB4 signaling
HRAS, KRAS, NRAS, NRG1
 Reactome 4 / 14 32.7× 5.16e-6 1.89e-4 ✓ sig.
GRB2 events in ERBB2 signaling
HRAS, KRAS, NRAS, NRG1
 Reactome 4 / 14 32.7× 5.16e-6 1.89e-4 ✓ sig.
Activation of RAS in B cells
HRAS, KRAS, NRAS
 Reactome 3 / 5 68.6× 6.41e-6 2.23e-4 ✓ sig.
Estrogen-stimulated signaling through PRKCZ
HRAS, KRAS, NRAS
 Reactome 3 / 6 57.2× 1.27e-5 4.00e-4 ✓ sig.
Longevity regulating pathway
HRAS, KRAS, NRAS, PPARG, PRKAG2, INSR, SOD2
 KEGG 7 / 90 8.9× 1.32e-5 4.10e-4 ✓ sig.
Longevity regulating pathway - multiple species
HRAS, KRAS, NRAS, PRKAG2, INSR, SOD2
 KEGG 6 / 62 11.1× 1.60e-5 4.83e-4 ✓ sig.
RAS signaling downstream of NF1 loss-of-function variants
HRAS, KRAS, NRAS
 Reactome 3 / 7 49.0× 2.22e-5 6.35e-4 ✓ sig.
FLT3 Signaling
HRAS, KRAS, NRAS
 Reactome 3 / 7 49.0× 2.22e-5 6.35e-4 ✓ sig.
Central carbon metabolism in cancer
HRAS, KRAS, NRAS, NTRK1, NTRK3, RET
 KEGG 6 / 71 9.7× 3.50e-5 9.27e-4 ✓ sig.
p38MAPK events
HRAS, KRAS, NRAS
 Reactome 3 / 8 42.9× 3.52e-5 9.33e-4 ✓ 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 ⇵
thyroid gland development
BRAF, FOXE1, NKX2-1, PAX8, TG, SMAD3
 GO:0030878 6 / 30 35.6× 1.45e-8 2.34e-6 ✓ sig.
cell surface receptor protein tyrosine kinase signaling pathway
ALK, NRG1, NTRK1, NTRK3, RET, GAB2, INSR
 GO:0007169 7 / 120 10.4× 5.11e-6 3.08e-4 ✓ sig.
positive regulation of gene expression
BRAF, HRAS, KRAS, MBIP, NKX2-1, NTRK3, PPARG, RET, TRIM24, SMAD3, TGFB2, BMP7
 GO:0010628 12 / 504 4.2× 2.61e-5 1.10e-3 ✓ sig.
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand
RET, WWOX, TGFB2
 GO:2001241 3 / 11 48.5× 2.75e-5 1.15e-3 ✓ sig.
positive regulation of DNA-templated transcription
FOXE1, NCOA4, NFIA, NKX2-1, PAX8, PPARG, RET, SKAP1, TRIM24, TRIM27, FGF7, INSR
 GO:0045893 15 / 778 3.4× 2.90e-5 1.20e-3 ✓ sig.
substantia propria of cornea development
KCNQ3, TGFB2
 GO:1903701 2 / 2 178× 3.13e-5 1.26e-3 ✓ sig.
telomere capping
STN1, POT1, TINF2
 GO:0016233 3 / 12 44.5× 3.66e-5 1.43e-3 ✓ sig.
neuron development
ALK, NTRK1, TENM4, TGFB2, SOD2
 GO:0048666 5 / 77 11.6× 7.29e-5 2.39e-3 ✓ sig.
telomere assembly
POT1, TINF2
 GO:0032202 2 / 3 119× 9.35e-5 2.88e-3 ✓ sig.
cellular response to estrogen stimulus
NCOA4, TRIM24, BCAS3
 GO:0071391 3 / 19 28.1× 1.56e-4 4.24e-3 ✓ sig.
MAPK cascade
BRAF, HRAS, KRAS, NRAS, RET, SMAD3
 GO:0000165 6 / 147 7.3× 1.82e-4 4.73e-3 ✓ sig.
regulation of transforming growth factor beta2 production
SMAD3, TGFB2
 GO:0032909 2 / 4 89.0× 1.86e-4 4.81e-3 ✓ sig.
response to isolation stress
KRAS, SOD2
 GO:0035900 2 / 4 89.0× 1.86e-4 4.81e-3 ✓ sig.
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
NTRK1, NTRK3, RET, VAV3, INSR, TGFB2, TMEM100
 GO:0051897 7 / 217 5.7× 2.25e-4 5.46e-3 ✓ sig.
negative regulation of telomere maintenance via telomerase
STN1, POT1, TINF2
 GO:0032211 3 / 22 24.3× 2.46e-4 5.84e-3 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Multinodular goiter Toxic nodular goiter 0.278 10 1.23e-24 2.93e-23 ✓ sig.
Differentiated thyroid carcinoma Thyroid carcinoma 0.135 7 7.57e-17 1.22e-15 ✓ sig.
Differentiated thyroid carcinoma Thyroid cancer 0.105 8 9.84e-14 1.27e-12 ✓ sig.
Thyroid cancer Toxic nodular goiter 0.130 6 8.85e-13 1.07e-11 ✓ sig.
Differentiated thyroid carcinoma Toxic nodular goiter 0.098 6 9.11e-12 1.00e-10 ✓ sig.
Thyroid cancer Thyroid carcinoma 0.073 3 8.19e-7 4.87e-6 ✓ sig.
Hurthle cell thyroid cancer Thyroid carcinoma 0.100 1 5.84e-4 1.16e-3 ✓ sig.
Differentiated thyroid carcinoma Hurthle cell thyroid cancer 0.020 1 3.18e-3 4.17e-3 ✓ sig.