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 251

7 diseases · 12 shared-gene connections
7 Diseases
16 Unique genes
0.201 Avg. similarity score
hemochromatosis type 1 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 ⇵
hemochromatosis type 1 5 5 1
Hepatic veno occlusive disease 4 4 7
Porphyruria 4 4 2
Variegate porphyria 4 4 4
Polymyalgia rheumatica 3 3 2
Porphyria cutanea tarda 3 3 7
porphyria due to ALA dehydratase deficiency 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
HFE 6 / 7 hemochromatosis type 1, Hepatic veno occlusive disease, Polymyalgia rheumatica, Porphyria cutanea tarda and 2 more
ALAD 2 / 7 Porphyria cutanea tarda, porphyria due to ALA dehydratase deficiency
GSTM1 2 / 7 Hepatic veno occlusive disease, Porphyria cutanea tarda
PPOX 2 / 7 Porphyruria, Variegate porphyria
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 ⇵
Heme biosynthesis
ALAD, CPOX, UROD, PPOX
 Reactome 4 / 14 214× 2.09e-9 2.13e-7 ✓ sig.
Porphyrin metabolism
ALAD, CPOX, UROD, PPOX
 KEGG 4 / 46 65.3× 3.31e-7 1.87e-5 ✓ sig.
Biosynthesis of protectins
CYP1A1, CYP1A2
 Reactome 2 / 4 375× 9.97e-6 3.34e-4 ✓ sig.
Biosynthesis of cofactors
ALAD, CPOX, UROD, PPOX
 KEGG 4 / 154 19.5× 4.20e-5 1.11e-3 ✓ sig.
Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)
CYP1A1, CYP1A2
 Reactome 2 / 8 188× 4.64e-5 1.20e-3 ✓ sig.
Metabolic pathways
GSTM1, MTHFR, ALAD, CPOX, CYP1A1, CYP1A2, UROD, PPOX, B4GALT3
 KEGG 9 / 1,563 4.3× 5.06e-5 1.29e-3 ✓ sig.
Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE)
CYP1A1, CYP1A2
 Reactome 2 / 9 167× 5.96e-5 1.47e-3 ✓ sig.
Chemical carcinogenesis - DNA adducts
GSTM1, CYP1A1, CYP1A2
 KEGG 3 / 70 32.2× 1.01e-4 2.27e-3 ✓ sig.
Metabolism of xenobiotics by cytochrome P450
GSTM1, CYP1A1, CYP1A2
 KEGG 3 / 79 28.5× 1.44e-4 3.02e-3 ✓ sig.
Aromatic amines can be N-hydroxylated or N-dealkylated by CYP1A2
CYP1A2
 Reactome 1 / 1 751× 1.33e-3 1.68e-2 ✓ sig.
Tryptophan metabolism
CYP1A1, CYP1A2
 KEGG 2 / 42 35.7× 1.39e-3 1.74e-2 ✓ sig.
Malaria
CSF3, THBS1
 KEGG 2 / 50 30.0× 1.96e-3 2.25e-2 ✓ sig.
Chemical carcinogenesis - receptor activation
GSTM1, CYP1A1, CYP1A2
 KEGG 3 / 215 10.5× 2.67e-3 2.83e-2 ✓ sig.
Steroid hormone biosynthesis
CYP1A1, CYP1A2
 KEGG 2 / 63 23.8× 3.10e-3 3.15e-2 ✓ sig.
Chemical carcinogenesis - reactive oxygen species
GSTM1, CYP1A1, CYP1A2
 KEGG 3 / 227 9.9× 3.11e-3 3.15e-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 ⇵
protoporphyrinogen IX biosynthetic process
ALAD, CPOX, UROD, PPOX
 GO:0006782 4 / 9 519× 4.50e-11 1.40e-8 ✓ sig.
heme O biosynthetic process
ALAD, CPOX, UROD, PPOX
 GO:0048034 4 / 9 519× 4.50e-11 1.40e-8 ✓ sig.
heme A biosynthetic process
ALAD, CPOX, UROD, PPOX
 GO:0006784 4 / 10 467× 7.50e-11 2.21e-8 ✓ sig.
heme B biosynthetic process
ALAD, CPOX, UROD, PPOX
 GO:0006785 4 / 10 467× 7.50e-11 2.21e-8 ✓ sig.
porphyrin-containing compound biosynthetic process
ALAD, CPOX, UROD, PPOX
 GO:0006779 4 / 11 425× 1.18e-10 3.33e-8 ✓ sig.
heme biosynthetic process
ALAD, CPOX, UROD, PPOX
 GO:0006783 4 / 27 173× 6.21e-9 1.13e-6 ✓ sig.
porphyrin-containing compound metabolic process
CYP1A1, CYP1A2, UROD
 GO:0006778 3 / 7 501× 1.80e-8 2.85e-6 ✓ sig.
response to arsenic-containing substance
ALAD, CPOX, CYP1A1
 GO:0046685 3 / 11 319× 8.46e-8 1.05e-5 ✓ sig.
response to iron ion
HFE, ALAD, CPOX
 GO:0010039 3 / 18 195× 4.17e-7 4.01e-5 ✓ sig.
response to xenobiotic stimulus
MTHFR, THBS1, ALAD, CYP1A1, PPOX
 GO:0009410 5 / 248 23.5× 1.53e-6 1.17e-4 ✓ sig.
xenobiotic catabolic process
GSTM1, CYP1A1, CYP1A2
 GO:0042178 3 / 28 125× 1.67e-6 1.25e-4 ✓ sig.
dibenzo-p-dioxin metabolic process
CYP1A1, CYP1A2
 GO:0018894 2 / 3 779× 2.06e-6 1.47e-4 ✓ sig.
olefinic compound metabolic process
CYP1A1, CYP1A2
 GO:0120254 2 / 4 584× 4.12e-6 2.57e-4 ✓ sig.
response to herbicide
ALAD, CYP1A1
 GO:0009635 2 / 5 467× 6.86e-6 3.86e-4 ✓ sig.
response to methylmercury
ALAD, CPOX
 GO:0051597 2 / 6 389× 1.03e-5 5.33e-4 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Porphyruria Variegate porphyria 0.400 2 5.06e-8 3.92e-7 ✓ sig.
Hepatic veno occlusive disease Porphyria cutanea tarda 0.154 2 3.72e-6 2.09e-5 ✓ sig.
hemochromatosis type 1 Polymyalgia rheumatica 0.333 1 1.30e-4 3.90e-4 ✓ sig.
hemochromatosis type 1 Porphyruria 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Polymyalgia rheumatica Porphyruria 0.250 1 2.60e-4 6.40e-4 ✓ sig.
hemochromatosis type 1 Variegate porphyria 0.200 1 2.60e-4 6.40e-4 ✓ sig.
hemochromatosis type 1 Hepatic veno occlusive disease 0.125 1 4.55e-4 9.55e-4 ✓ sig.
hemochromatosis type 1 Porphyria cutanea tarda 0.125 1 4.55e-4 9.55e-4 ✓ sig.
Porphyria cutanea tarda porphyria due to ALA dehydratase deficiency 0.125 1 4.55e-4 9.55e-4 ✓ sig.
Polymyalgia rheumatica Variegate porphyria 0.167 1 5.19e-4 1.04e-3 ✓ sig.
Hepatic veno occlusive disease Porphyruria 0.111 1 9.09e-4 1.56e-3 ✓ sig.
Hepatic veno occlusive disease Variegate porphyria 0.091 1 1.82e-3 2.66e-3 ✓ sig.