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 232
7
Diseases
4
Unique genes
0.317
Avg. similarity score
Hepatic methionine adenosyltransferase deficiency
Most-connected disease (5 links)
Disease
Searched: Adenosine kinase deficiency
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Adenosine kinase deficiency
Hepatic methionine adenosyltransferase deficiency
S-adenosylhomocysteine hydrolase deficiency
Sulfur amino acid metabolism disorder
Glycine n-methyltransferase deficiency
hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase
methionine adenosyltransferase deficiency
Member diseases (most connected first ‐ the cluster's core)
| Disease ⇵ | Connections in cluster ⇵ | Significant partners ⇵ | Curated genes ⇵ |
|---|---|---|---|
| Hepatic methionine adenosyltransferase deficiency | 5 | 5 | 3 |
| S-adenosylhomocysteine hydrolase deficiency | 5 | 5 | 3 |
| Sulfur amino acid metabolism disorder | 5 | 5 | 3 |
| Glycine n-methyltransferase deficiency | 3 | 3 | 1 |
| hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase | 3 | 3 | 1 |
| methionine adenosyltransferase deficiency | 2 | 2 | 1 |
| Adenosine kinase deficiency | 1 | 1 | 1 |
Top shared genes (genes linked to 2+ member diseases)
| Gene ⇵ | Member diseases ⇵ | Linked diseases |
|---|---|---|
| AHCY | 4 / 7 | Hepatic methionine adenosyltransferase deficiency, hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase, S-adenosylhomocysteine hydrolase deficiency, Sulfur amino acid metabolism disorder |
| GNMT | 4 / 7 | Glycine n-methyltransferase deficiency, Hepatic methionine adenosyltransferase deficiency, S-adenosylhomocysteine hydrolase deficiency, Sulfur amino acid metabolism disorder |
| MAT1A | 3 / 7 | Hepatic methionine adenosyltransferase deficiency, methionine adenosyltransferase deficiency, S-adenosylhomocysteine hydrolase deficiency |
| ADK | 2 / 7 | Adenosine kinase deficiency, Sulfur amino acid metabolism disorder |
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 ⇵ |
|---|---|---|---|---|---|
| One carbon pool by folate | KEGG | 3 / 38 | 237× | 1.17e-7 | 7.48e-6 ✓ sig. |
| Cysteine and methionine metabolism | KEGG | 3 / 52 | 173× | 3.05e-7 | 1.74e-5 ✓ sig. |
| Sulfur amino acid metabolism | Reactome | 2 / 6 | 1,001× | 1.25e-6 | 5.89e-5 ✓ sig. |
| Methylation | Reactome | 2 / 14 | 429× | 7.56e-6 | 2.72e-4 ✓ sig. |
| Metabolic pathways | KEGG | 4 / 1,563 | 7.7× | 2.86e-4 | 5.24e-3 ✓ sig. |
| Defective AHCY causes Hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency (HMAHCHD) | Reactome | 1 / 1 | 3,003× | 3.33e-4 | 5.91e-3 ✓ sig. |
| Defective MAT1A causes Methionine adenosyltransferase deficiency (MATD) | Reactome | 1 / 1 | 3,003× | 3.33e-4 | 5.91e-3 ✓ sig. |
| Metabolism of ingested SeMet, Sec, MeSec into H2Se | Reactome | 1 / 2 | 1,501× | 6.66e-4 | 1.02e-2 ✓ sig. |
| Purine salvage | Reactome | 1 / 13 | 231× | 4.32e-3 | 4.04e-2 ✓ sig. |
| Glyoxylate metabolism and glycine degradation | Reactome | 1 / 28 | 107× | 9.29e-3 | 6.69e-2 |
| Glycine, serine and threonine metabolism | KEGG | 1 / 40 | 75.1× | 1.33e-2 | 8.31e-2 |
| Biosynthesis of amino acids | KEGG | 1 / 75 | 40.0× | 2.47e-2 | 1.20e-1 |
| Nucleotide metabolism | KEGG | 1 / 85 | 35.3× | 2.80e-2 | 1.28e-1 |
| Purine metabolism | KEGG | 1 / 128 | 23.5× | 4.20e-2 | 1.59e-1 |
| Biosynthesis of cofactors | KEGG | 1 / 154 | 19.5× | 5.03e-2 | 1.75e-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 ⇵ |
|---|---|---|---|---|---|
| one-carbon metabolic process | GO:0006730 | 3 / 21 | 667× | 4.89e-9 | 8.91e-7 ✓ sig. |
| protein homotetramerization | GO:0051289 | 2 / 66 | 142× | 7.34e-5 | 2.45e-3 ✓ sig. |
| dATP biosynthetic process | GO:0006175 | 1 / 1 | 4,672× | 2.14e-4 | 5.39e-3 ✓ sig. |
| L-methionine catabolic process | GO:0009087 | 1 / 1 | 4,672× | 2.14e-4 | 5.39e-3 ✓ sig. |
| sarcosine metabolic process | GO:1901052 | 1 / 1 | 4,672× | 2.14e-4 | 5.39e-3 ✓ sig. |
| S-adenosylhomocysteine metabolic process | GO:0046498 | 1 / 2 | 2,336× | 4.28e-4 | 8.77e-3 ✓ sig. |
| dAMP salvage | GO:0106383 | 1 / 3 | 1,557× | 6.42e-4 | 1.15e-2 ✓ sig. |
| ribonucleoside monophosphate biosynthetic process | GO:0009156 | 1 / 4 | 1,168× | 8.56e-4 | 1.39e-2 ✓ sig. |
| S-adenosylmethionine cycle | GO:0033353 | 1 / 4 | 1,168× | 8.56e-4 | 1.39e-2 ✓ sig. |
| S-adenosylmethionine biosynthetic process | GO:0006556 | 1 / 4 | 1,168× | 8.56e-4 | 1.39e-2 ✓ sig. |
| S-adenosylmethionine metabolic process | GO:0046500 | 1 / 4 | 1,168× | 8.56e-4 | 1.39e-2 ✓ sig. |
| GMP salvage | GO:0032263 | 1 / 5 | 934× | 1.07e-3 | 1.60e-2 ✓ sig. |
| AMP salvage | GO:0044209 | 1 / 6 | 779× | 1.28e-3 | 1.79e-2 ✓ sig. |
| methionine metabolic process | GO:0006555 | 1 / 6 | 779× | 1.28e-3 | 1.79e-2 ✓ sig. |
| purine nucleobase metabolic process | GO:0006144 | 1 / 7 | 667× | 1.50e-3 | 1.95e-2 ✓ sig. |