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 164

10 diseases · 30 shared-gene connections
10 Diseases
21 Unique genes
0.312 Avg. similarity score
B-cell lymphopenia Most-connected disease (8 links)
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Disease Searched: Hypocellular bone marrow 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 ⇵
B-cell lymphopenia 8 8 1
Digit abnormalities 8 8 1
Hypocellular bone marrow 8 8 1
MECOM-associated syndrome 8 8 1
Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 7 7 1
Hypogammaglobulinemia 6 6 4
Radioulnar synostosis 5 5 3
Radioulnar synostosis with amegakaryocytic thrombocytopenia 1 5 5 2
Hyperpituitarism 4 4 15
Immunodeficiency 82 with systemic inflammation 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
MECOM 9 / 10 B-cell lymphopenia, Digit abnormalities, Hyperpituitarism, Hypocellular bone marrow and 5 more
SYK 2 / 10 Hypogammaglobulinemia, Immunodeficiency 82 with systemic inflammation
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 ⇵
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
CD19, SYK
 Reactome 2 / 23 49.7× 7.21e-4 8.37e-3 ✓ sig.
Lysine degradation
MECOM, KMT2D
 KEGG 2 / 63 18.2× 5.33e-3 3.65e-2 ✓ sig.
PKMTs methylate histone lysines
MECOM, KMT2D
 Reactome 2 / 71 16.1× 6.73e-3 4.25e-2 ✓ sig.
Fc epsilon receptor (FCERI) signaling
SYK
 Reactome 1 / 6 95.3× 1.04e-2 5.63e-2
B cell receptor signaling pathway
CD19, SYK
 KEGG 2 / 91 12.6× 1.09e-2 5.79e-2
RUNX2 regulates bone development
SMAD6
 Reactome 1 / 7 81.7× 1.22e-2 6.20e-2
Hematopoietic cell lineage
IL1R1, CD19
 KEGG 2 / 100 11.4× 1.30e-2 6.44e-2
Conjugation of salicylate with glycine
ACSM2A
 Reactome 1 / 8 71.5× 1.39e-2 6.72e-2
NF-kappa B signaling pathway
IL1R1, SYK
 KEGG 2 / 105 10.9× 1.43e-2 6.83e-2
Interleukin-2 signaling
SYK
 Reactome 1 / 12 47.7× 2.08e-2 8.54e-2
FCGR activation
SYK
 Reactome 1 / 12 47.7× 2.08e-2 8.54e-2
Osteoclast differentiation
IL1R1, SYK
 KEGG 2 / 142 8.1× 2.52e-2 9.61e-2
Role of LAT2/NTAL/LAB on calcium mobilization
SYK
 Reactome 1 / 15 38.1× 2.59e-2 9.76e-2
Role of phospholipids in phagocytosis
SYK
 Reactome 1 / 21 27.2× 3.61e-2 1.18e-1
Regulation of signaling by CBL
SYK
 Reactome 1 / 21 27.2× 3.61e-2 1.18e-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 ⇵
response to estrogen
HOXA11, KMT2D, SMAD6
 GO:0043627 3 / 49 54.5× 2.18e-5 9.63e-4 ✓ sig.
embryonic skeletal joint morphogenesis
HOXA11, OSR2
 GO:0060272 2 / 11 162× 6.58e-5 2.22e-3 ✓ sig.
embryonic forelimb morphogenesis
HOXA11, OSR2
 GO:0035115 2 / 33 53.9× 6.22e-4 1.08e-2 ✓ sig.
metanephros development
HOXA11, OSR2
 GO:0001656 2 / 38 46.8× 8.25e-4 1.28e-2 ✓ sig.
daunorubicin transport
ABCB1
 GO:0043215 1 / 1 890× 1.12e-3 1.53e-2 ✓ sig.
terpenoid transport
ABCB1
 GO:0046865 1 / 1 890× 1.12e-3 1.53e-2 ✓ sig.
cellular response to nonylphenol
ABCB1
 GO:1904148 1 / 1 890× 1.12e-3 1.53e-2 ✓ sig.
positive regulation of establishment of Sertoli cell barrier
ABCB1
 GO:1904446 1 / 1 890× 1.12e-3 1.53e-2 ✓ sig.
cellular response to borneol
ABCB1
 GO:1905231 1 / 1 890× 1.12e-3 1.53e-2 ✓ sig.
response to codeine
ABCB1
 GO:1905233 1 / 1 890× 1.12e-3 1.53e-2 ✓ sig.
response to quercetin
ABCB1
 GO:1905235 1 / 1 890× 1.12e-3 1.53e-2 ✓ sig.
positive regulation of response to drug
ABCB1
 GO:2001025 1 / 1 890× 1.12e-3 1.53e-2 ✓ sig.
positive regulation of interleukin-1-mediated signaling pathway
IL1R1
 GO:2000661 1 / 1 890× 1.12e-3 1.53e-2 ✓ sig.
serotonin secretion
SYK
 GO:0001820 1 / 1 890× 1.12e-3 1.53e-2 ✓ sig.
positive regulation of interleukin-3 production
SYK
 GO:0032752 1 / 1 890× 1.12e-3 1.53e-2 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
B-cell lymphopenia Hypocellular bone marrow 0.500 1 6.46e-5 1.98e-4 ✓ sig.
B-cell lymphopenia Digit abnormalities 0.500 1 6.46e-5 1.98e-4 ✓ sig.
B-cell lymphopenia Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 0.500 1 6.46e-5 1.98e-4 ✓ sig.
B-cell lymphopenia MECOM-associated syndrome 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Digit abnormalities MECOM-associated syndrome 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Digit abnormalities Hypocellular bone marrow 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Digit abnormalities Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 0.500 1 6.46e-5 1.98e-4 ✓ sig.
MECOM-associated syndrome Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Hypocellular bone marrow Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Hypocellular bone marrow MECOM-associated syndrome 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Radioulnar synostosis with amegakaryocytic thrombocytopenia 1 Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 0.333 1 1.29e-4 3.27e-4 ✓ sig.
MECOM-associated syndrome Radioulnar synostosis with amegakaryocytic thrombocytopenia 1 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Hypocellular bone marrow Radioulnar synostosis with amegakaryocytic thrombocytopenia 1 0.333 1 1.29e-4 3.27e-4 ✓ sig.
B-cell lymphopenia Radioulnar synostosis with amegakaryocytic thrombocytopenia 1 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Digit abnormalities Radioulnar synostosis with amegakaryocytic thrombocytopenia 1 0.333 1 1.29e-4 3.27e-4 ✓ sig.
Radioulnar synostosis Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 0.250 1 1.94e-4 4.41e-4 ✓ sig.
B-cell lymphopenia Radioulnar synostosis 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Digit abnormalities Radioulnar synostosis 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Hypocellular bone marrow Radioulnar synostosis 0.250 1 1.94e-4 4.41e-4 ✓ sig.
MECOM-associated syndrome Radioulnar synostosis 0.250 1 1.94e-4 4.41e-4 ✓ sig.
Hypogammaglobulinemia Immunodeficiency 82 with systemic inflammation 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Hypogammaglobulinemia Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 0.200 1 2.58e-4 5.38e-4 ✓ sig.
B-cell lymphopenia Hypogammaglobulinemia 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Digit abnormalities Hypogammaglobulinemia 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Hypocellular bone marrow Hypogammaglobulinemia 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Hypogammaglobulinemia MECOM-associated syndrome 0.200 1 2.58e-4 5.38e-4 ✓ sig.
B-cell lymphopenia Hyperpituitarism 0.063 1 9.68e-4 1.50e-3 ✓ sig.
Hyperpituitarism MECOM-associated syndrome 0.063 1 9.68e-4 1.50e-3 ✓ sig.
Hyperpituitarism Hypocellular bone marrow 0.063 1 9.68e-4 1.50e-3 ✓ sig.
Digit abnormalities Hyperpituitarism 0.063 1 9.68e-4 1.50e-3 ✓ sig.