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 236

7 diseases · 15 shared-gene connections
7 Diseases
31 Unique genes
0.236 Avg. similarity score
Alpha-1 antitrypsin deficiency Most-connected disease (5 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 ⇵
Alpha-1 antitrypsin deficiency 5 5 1
Beriberi 5 5 1
Gastro-entero-pancreatic neuroendocrine tumor 5 5 15
Panniculitis 5 5 1
Thiamine deficiency 5 5 1
Asbestosis 4 4 17
immunodeficiency 63 with lymphoproliferation and autoimmunity 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
SERPINA1 6 / 7 Alpha-1 antitrypsin deficiency, Asbestosis, Beriberi, Gastro-entero-pancreatic neuroendocrine tumor and 2 more
IL2RB 2 / 7 Gastro-entero-pancreatic neuroendocrine tumor, immunodeficiency 63 with lymphoproliferation and autoimmunity
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 ⇵
Amoebiasis
ARG1, IL1B, NOS2, PRDX1, TNF, IL10
 KEGG 6 / 103 22.6× 2.13e-7 1.26e-5 ✓ sig.
Lipid and atherosclerosis
ATF6, DDIT3, HSPA5, IL1B, NLRP3, TNF, POU2F2
 KEGG 7 / 216 12.6× 1.01e-6 4.90e-5 ✓ sig.
Pertussis
IL1B, NLRP3, NOS2, TNF, IL10
 KEGG 5 / 78 24.8× 1.51e-6 6.96e-5 ✓ sig.
Interleukin-10 signaling
IL1B, TNF, CD86, IL10
 Reactome 4 / 47 33.0× 5.99e-6 2.20e-4 ✓ sig.
Interleukin-4 and Interleukin-13 signaling
IL1B, NOS2, TNF, GATA3, IL10
 Reactome 5 / 108 17.9× 7.56e-6 2.65e-4 ✓ sig.
Inflammatory bowel disease
IL1B, TNF, GATA3, IL10
 KEGG 4 / 66 23.5× 2.34e-5 6.79e-4 ✓ sig.
ATF6 (ATF6-alpha) activates chaperones
ATF6, HSPA5
 Reactome 2 / 4 194× 3.86e-5 1.03e-3 ✓ sig.
Leishmaniasis
IL1B, NOS2, TNF, IL10
 KEGG 4 / 78 19.9× 4.53e-5 1.18e-3 ✓ sig.
RUNX3 Regulates Immune Response and Cell Migration
SPP1, RUNX3
 Reactome 2 / 5 155× 6.42e-5 1.56e-3 ✓ sig.
Th1 and Th2 cell differentiation
GATA3, IL2RB, NOTCH2, RUNX3
 KEGG 4 / 93 16.7× 9.03e-5 2.07e-3 ✓ sig.
Tuberculosis
IL1B, NOS2, TNF, CIITA, IL10
 KEGG 5 / 181 10.7× 9.09e-5 2.08e-3 ✓ sig.
African trypanosomiasis
IL1B, TNF, IL10
 KEGG 3 / 37 31.4× 1.14e-4 2.49e-3 ✓ sig.
Allograft rejection
TNF, CD86, IL10
 KEGG 3 / 39 29.8× 1.34e-4 2.83e-3 ✓ sig.
Chagas disease
IL1B, NOS2, TNF, IL10
 KEGG 4 / 103 15.0× 1.34e-4 2.85e-3 ✓ sig.
C-type lectin receptor signaling pathway
IL1B, NLRP3, TNF, IL10
 KEGG 4 / 105 14.8× 1.45e-4 3.03e-3 ✓ 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 ⇵
cellular response to lipopolysaccharide
IL1B, NLRP3, NOS2, TNF, CD86, GFI1, IL10
 GO:0071222 7 / 187 22.6× 1.93e-8 3.02e-6 ✓ sig.
positive regulation of transcription by RNA polymerase II
ATF6, DDIT3, HSPA5, IL1B, NLRP3, TNF, CIITA, EOMES, GATA3, IKZF3, IL10, NOTCH2
 GO:0045944 13 / 1,208 6.5× 2.22e-8 3.42e-6 ✓ sig.
positive regulation of immunoglobulin production
TNF, CD86, IL10, PTPRC
 GO:0002639 4 / 33 73.1× 2.45e-7 2.57e-5 ✓ sig.
cell redox homeostasis
DDIT3, NOS2, PRDX1, PRDX2
 GO:0045454 4 / 44 54.8× 8.03e-7 6.94e-5 ✓ sig.
positive regulation of heterotypic cell-cell adhesion
IL1B, TNF, IL10
 GO:0034116 3 / 13 139× 1.17e-6 9.40e-5 ✓ sig.
positive regulation of miRNA transcription
TNF, GATA3, IL10, NOTCH2
 GO:1902895 4 / 56 43.1× 2.14e-6 1.52e-4 ✓ sig.
humoral immune response
TNF, GATA3, NOTCH2, POU2F2
 GO:0006959 4 / 58 41.6× 2.47e-6 1.71e-4 ✓ sig.
chronic inflammatory response to antigenic stimulus
TNF, IL10
 GO:0002439 2 / 2 603× 2.66e-6 1.81e-4 ✓ sig.
positive regulation of DNA-templated transcription
DDIT3, IL1B, SPP1, TNF, CD86, EOMES, GATA3, IL10, RUNX3
 GO:0045893 9 / 778 7.0× 3.17e-6 2.09e-4 ✓ sig.
positive regulation of interleukin-8 production
DDIT3, IL1B, NOS2, TNF
 GO:0032757 4 / 65 37.1× 3.91e-6 2.47e-4 ✓ sig.
positive regulation of non-canonical NF-kappaB signal transduction
IL1B, NLRP3, TNF, CD86
 GO:1901224 4 / 66 36.5× 4.16e-6 2.59e-4 ✓ sig.
response to lipopolysaccharide
IL1B, NOS2, PRDX2, TNF, IL10
 GO:0032496 5 / 161 18.7× 6.32e-6 3.62e-4 ✓ sig.
regulation of ATF6-mediated unfolded protein response
ATF6, HSPA5
 GO:1903891 2 / 3 402× 7.98e-6 4.37e-4 ✓ sig.
positive regulation of T cell mediated immunity
IL1B, PTPRC
 GO:0002711 2 / 3 402× 7.98e-6 4.37e-4 ✓ sig.
positive regulation of cytokine production
IL1B, TNF, GATA3, IL10
 GO:0001819 4 / 81 29.8× 9.43e-6 4.99e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Alpha-1 antitrypsin deficiency Beriberi 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Alpha-1 antitrypsin deficiency Panniculitis 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Alpha-1 antitrypsin deficiency Thiamine deficiency 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Beriberi Panniculitis 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Beriberi Thiamine deficiency 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Panniculitis Thiamine deficiency 0.500 1 6.49e-5 2.34e-4 ✓ sig.
Alpha-1 antitrypsin deficiency Gastro-entero-pancreatic neuroendocrine tumor 0.063 1 9.74e-4 1.64e-3 ✓ sig.
Beriberi Gastro-entero-pancreatic neuroendocrine tumor 0.063 1 9.74e-4 1.64e-3 ✓ sig.
Gastro-entero-pancreatic neuroendocrine tumor Panniculitis 0.063 1 9.74e-4 1.64e-3 ✓ sig.
Gastro-entero-pancreatic neuroendocrine tumor immunodeficiency 63 with lymphoproliferation and autoimmunity 0.063 1 9.74e-4 1.64e-3 ✓ sig.
Gastro-entero-pancreatic neuroendocrine tumor Thiamine deficiency 0.063 1 9.74e-4 1.64e-3 ✓ sig.
Alpha-1 antitrypsin deficiency Asbestosis 0.056 1 1.10e-3 1.81e-3 ✓ sig.
Asbestosis Beriberi 0.056 1 1.10e-3 1.81e-3 ✓ sig.
Asbestosis Panniculitis 0.056 1 1.10e-3 1.81e-3 ✓ sig.
Asbestosis Thiamine deficiency 0.056 1 1.10e-3 1.81e-3 ✓ sig.