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 327

6 diseases · 8 shared-gene connections
6 Diseases
5 Unique genes
0.277 Avg. similarity score
Arthralgia Most-connected disease (4 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 ⇵
Arthralgia 4 4 2
Hyper-immunoglobulin d syndrome 4 4 4
Hyper-igd syndrome 3 3 1
Mevalonate kinase deficiency 3 3 2
Bone marrow neoplasms 1 1 1
methylmalonic aciduria, cblb type 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
MVK 4 / 6 Arthralgia, Hyper-igd syndrome, Hyper-immunoglobulin d syndrome, Mevalonate kinase deficiency
CSF3 2 / 6 Arthralgia, Bone marrow neoplasms
HMGCR 2 / 6 Hyper-immunoglobulin d syndrome, Mevalonate kinase deficiency
MMAB 2 / 6 Hyper-immunoglobulin d syndrome, methylmalonic aciduria, cblb type
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 ⇵
Cholesterol biosynthesis
MVK, HMGCR
 Reactome 2 / 21 229× 2.90e-5 8.11e-4 ✓ sig.
Terpenoid backbone biosynthesis
MVK, HMGCR
 KEGG 2 / 23 209× 3.50e-5 9.50e-4 ✓ sig.
Activation of gene expression by SREBF (SREBP)
MVK, HMGCR
 Reactome 2 / 42 114× 1.19e-4 2.57e-3 ✓ sig.
Defective MMAB causes methylmalonic aciduria type cblB
MMAB
 Reactome 1 / 1 2,402× 4.16e-4 6.90e-3 ✓ sig.
Cobalamin transport and metabolism
MMAB
 KEGG 1 / 18 133× 7.47e-3 5.69e-2
EGR2 and SOX10-mediated initiation of Schwann cell myelination
HMGCR
 Reactome 1 / 20 120× 8.30e-3 6.10e-2
Cobalamin (Cbl, vitamin B12) transport and metabolism
MMAB
 Reactome 1 / 21 114× 8.71e-3 6.31e-2
Other interleukin signaling
CSF3
 Reactome 1 / 24 100× 9.95e-3 6.82e-2
Metabolic pathways
MVK, HMGCR, MMAB
 KEGG 3 / 1,563 4.6× 1.79e-2 9.70e-2
Porphyrin metabolism
MMAB
 KEGG 1 / 46 52.2× 1.90e-2 9.99e-2
Interleukin-10 signaling
CSF3
 Reactome 1 / 47 51.1× 1.94e-2 1.01e-1
Malaria
CSF3
 KEGG 1 / 50 48.0× 2.06e-2 1.05e-1
Peroxisome
MVK
 KEGG 1 / 83 28.9× 3.41e-2 1.39e-1
Bile secretion
HMGCR
 KEGG 1 / 90 26.7× 3.69e-2 1.45e-1
IL-17 signaling pathway
CSF3
 KEGG 1 / 94 25.6× 3.85e-2 1.48e-1

Enriched GO Terms (Biological Process, a second line of biological evidence)

GO term ⇵ GO ID ⇵ Overlap genes ⇵ Fold enrichment ⇵ P-value ⇵ FDR q-value ⇵
isoprenoid biosynthetic process
MVK, HMGCR
 GO:0008299 2 / 13 575× 4.46e-6 2.74e-4 ✓ sig.
sterol biosynthetic process
MVK, HMGCR
 GO:0016126 2 / 31 241× 2.66e-5 1.11e-3 ✓ sig.
cholesterol biosynthetic process
MVK, HMGCR
 GO:0006695 2 / 39 192× 4.23e-5 1.59e-3 ✓ sig.
steroid biosynthetic process
MVK, HMGCR
 GO:0006694 2 / 65 115× 1.18e-4 3.43e-3 ✓ sig.
cholesterol metabolic process
MVK, HMGCR
 GO:0008203 2 / 107 69.9× 3.21e-4 7.03e-3 ✓ sig.
steroid metabolic process
MVK, HMGCR
 GO:0008202 2 / 135 55.4× 5.11e-4 9.70e-3 ✓ sig.
isopentenyl diphosphate biosynthetic process, mevalonate pathway
MVK
 GO:0019287 1 / 3 1,246× 8.03e-4 1.30e-2 ✓ sig.
positive regulation of myeloid cell differentiation
CSF3
 GO:0045639 1 / 5 747× 1.34e-3 1.79e-2 ✓ sig.
coenzyme A metabolic process
HMGCR
 GO:0015936 1 / 5 747× 1.34e-3 1.79e-2 ✓ sig.
granulocyte colony-stimulating factor signaling pathway
CSF3
 GO:0038158 1 / 5 747× 1.34e-3 1.79e-2 ✓ sig.
cobalamin metabolic process
MMAB
 GO:0009235 1 / 9 415× 2.41e-3 2.50e-2 ✓ sig.
regulation of SNARE complex assembly
VPS41
 GO:0035542 1 / 12 311× 3.21e-3 2.91e-2 ✓ sig.
negative regulation of amyloid-beta clearance
HMGCR
 GO:1900222 1 / 12 311× 3.21e-3 2.91e-2 ✓ sig.
regulation of actin filament organization
CSF3
 GO:0110053 1 / 13 287× 3.47e-3 3.06e-2 ✓ sig.
protein targeting to vacuole
VPS41
 GO:0006623 1 / 14 267× 3.74e-3 3.18e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Hyper-immunoglobulin d syndrome Mevalonate kinase deficiency 0.400 2 5.06e-8 3.92e-7 ✓ sig.
Arthralgia Hyper-igd syndrome 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Arthralgia Bone marrow neoplasms 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Hyper-igd syndrome Mevalonate kinase deficiency 0.333 1 1.30e-4 3.90e-4 ✓ sig.
Arthralgia Mevalonate kinase deficiency 0.250 1 2.60e-4 6.40e-4 ✓ sig.
Hyper-igd syndrome Hyper-immunoglobulin d syndrome 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Hyper-immunoglobulin d syndrome methylmalonic aciduria, cblb type 0.200 1 2.60e-4 6.40e-4 ✓ sig.
Arthralgia Hyper-immunoglobulin d syndrome 0.167 1 5.19e-4 1.04e-3 ✓ sig.