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 521

5 diseases · 7 shared-gene connections
5 Diseases
4 Unique genes
0.329 Avg. similarity score
Hyperphenylalaninemia 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 ⇵
Hyperphenylalaninemia 4 4 4
Phenylalanine hydroxylase deficiency 3 3 1
Phenylketonuria 3 3 1
Tetrahydrobiopterin-responsive phenylketonuria 3 3 1
6-pyruvoyltetrahydropterin synthase deficiency 1 1 1

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

Gene ⇵ Member diseases ⇵ Linked diseases
PAH 4 / 5 Hyperphenylalaninemia, Phenylalanine hydroxylase deficiency, Phenylketonuria, Tetrahydrobiopterin-responsive phenylketonuria
PTS 2 / 5 6-pyruvoyltetrahydropterin synthase deficiency, Hyperphenylalaninemia
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 ⇵
Folate biosynthesis
PTS, SPR, PAH
 KEGG 3 / 28 322× 4.53e-8 2.79e-6 ✓ sig.
Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation
PTS, SPR
 Reactome 2 / 11 546× 4.57e-6 1.53e-4 ✓ sig.
Phenylketonuria
PAH
 Reactome 1 / 1 3,003× 3.33e-4 4.88e-3 ✓ sig.
Biosynthesis of cofactors
PTS, SPR
 KEGG 2 / 154 39.0× 9.64e-4 1.10e-2 ✓ sig.
Phenylalanine, tyrosine and tryptophan biosynthesis
PAH
 KEGG 1 / 6 500× 2.00e-3 1.90e-2 ✓ sig.
Phenylalanine metabolism
PAH
 Reactome 1 / 6 500× 2.00e-3 1.90e-2 ✓ sig.
eNOS activation
SPR
 Reactome 1 / 13 231× 4.32e-3 3.30e-2 ✓ sig.
Phenylalanine metabolism
PAH
 KEGG 1 / 16 188× 5.32e-3 3.80e-2 ✓ sig.
Metabolic pathways
PTS, SPR, PAH
 KEGG 3 / 1,563 5.8× 7.94e-3 4.94e-2 ✓ sig.
Biosynthesis of amino acids
PAH
 KEGG 1 / 75 40.0× 2.47e-2 9.68e-2

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

GO term ⇵ GO ID ⇵ Overlap genes ⇵ Fold enrichment ⇵ P-value ⇵ FDR q-value ⇵
tetrahydrobiopterin biosynthetic process
PTS, SPR
 GO:0006729 2 / 8 1,168× 9.62e-7 8.33e-5 ✓ sig.
tyrosine biosynthetic process
PAH
 GO:0006571 1 / 1 4,672× 2.14e-4 5.31e-3 ✓ sig.
tyrosine biosynthetic process, by oxidation of phenylalanine
PAH
 GO:0019293 1 / 2 2,336× 4.28e-4 8.53e-3 ✓ sig.
tetrahydrobiopterin metabolic process
PTS
 GO:0046146 1 / 4 1,168× 8.56e-4 1.33e-2 ✓ sig.
catecholamine biosynthetic process
PAH
 GO:0042423 1 / 6 779× 1.28e-3 1.67e-2 ✓ sig.
L-phenylalanine catabolic process
PAH
 GO:0006559 1 / 8 584× 1.71e-3 1.96e-2 ✓ sig.
aromatic amino acid metabolic process
PAH
 GO:0009072 1 / 10 467× 2.14e-3 2.19e-2 ✓ sig.
nitric oxide biosynthetic process
SPR
 GO:0006809 1 / 23 203× 4.91e-3 3.31e-2 ✓ sig.
amino acid biosynthetic process
PAH
 GO:0008652 1 / 27 173× 5.77e-3 3.56e-2 ✓ sig.
amino acid metabolic process
PTS
 GO:0006520 1 / 37 126× 7.90e-3 4.16e-2 ✓ sig.
central nervous system development
PTS
 GO:0007417 1 / 158 29.6× 3.34e-2 8.55e-2

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Phenylalanine hydroxylase deficiency Phenylketonuria 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Phenylalanine hydroxylase deficiency Tetrahydrobiopterin-responsive phenylketonuria 0.500 1 6.46e-5 1.98e-4 ✓ sig.
Phenylketonuria Tetrahydrobiopterin-responsive phenylketonuria 0.500 1 6.46e-5 1.98e-4 ✓ sig.
6-pyruvoyltetrahydropterin synthase deficiency Hyperphenylalaninemia 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Hyperphenylalaninemia Phenylketonuria 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Hyperphenylalaninemia Tetrahydrobiopterin-responsive phenylketonuria 0.200 1 2.58e-4 5.38e-4 ✓ sig.
Hyperphenylalaninemia Phenylalanine hydroxylase deficiency 0.200 1 2.58e-4 5.38e-4 ✓ sig.