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Add scVelo RNA velocity analysis workflow and IQ-TREE reference documentation
- Introduced a comprehensive RNA velocity analysis pipeline using scVelo, including data loading, preprocessing, velocity estimation, and visualization. - Added a script for running RNA velocity analysis with customizable parameters and output options. - Created detailed documentation for IQ-TREE 2 phylogenetic inference, covering command syntax, model selection, bootstrapping methods, and output interpretation. - Included references for velocity models and their mathematical framework, along with a comparison of different models. - Enhanced the scVelo skill documentation with installation instructions, use cases, and best practices for RNA velocity analysis.
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# HPO and Disease Ontology Reference for Monarch
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## Human Phenotype Ontology (HPO)
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### HPO Structure
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HPO is organized hierarchically:
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- **Root**: HP:0000001 (All)
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- HP:0000118 (Phenotypic abnormality)
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- HP:0000478 (Abnormality of the eye)
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- HP:0000707 (Abnormality of the nervous system)
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- HP:0001507 (Growth abnormality)
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- HP:0001626 (Abnormality of the cardiovascular system)
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- etc.
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### Top-Level HPO Categories
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| HPO ID | Name |
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|--------|------|
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| HP:0000924 | Abnormality of the skeletal system |
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| HP:0000707 | Abnormality of the nervous system |
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| HP:0000478 | Abnormality of the eye |
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| HP:0000598 | Abnormality of the ear |
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| HP:0001507 | Growth abnormality |
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| HP:0001626 | Abnormality of the cardiovascular system |
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| HP:0002086 | Abnormality of the respiratory system |
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| HP:0001939 | Abnormality of metabolism/homeostasis |
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| HP:0002664 | Neoplasm |
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| HP:0000818 | Abnormality of the endocrine system |
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| HP:0000119 | Abnormality of the genitourinary system |
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| HP:0001197 | Abnormality of prenatal development/birth |
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### Common HPO Terms in Rare Disease Genetics
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#### Neurological
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| HPO ID | Term |
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|--------|------|
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| HP:0001250 | Seizures |
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| HP:0001251 | Ataxia |
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| HP:0001252 | Muscular hypotonia |
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| HP:0001263 | Global developmental delay |
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| HP:0001270 | Motor delay |
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| HP:0002167 | Neurological speech impairment |
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| HP:0000716 | Depressivity |
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| HP:0000729 | Autistic behavior |
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| HP:0001332 | Dystonia |
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| HP:0002071 | Abnormality of extrapyramidal motor function |
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#### Growth/Morphology
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| HPO ID | Term |
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|--------|------|
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| HP:0004322 | Short stature |
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| HP:0001508 | Failure to thrive |
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| HP:0000252 | Microcephaly |
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| HP:0000256 | Macrocephaly |
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| HP:0001511 | Intrauterine growth retardation |
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#### Facial Features
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| HPO ID | Term |
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|--------|------|
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| HP:0000324 | Facial asymmetry |
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| HP:0001249 | Intellectual disability |
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| HP:0000219 | Thin upper lip vermilion |
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| HP:0000303 | Mandibular prognathia |
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| HP:0000463 | Anteverted nares |
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#### Metabolic
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| HPO ID | Term |
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|--------|------|
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| HP:0001943 | Hypoglycemia |
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| HP:0001944 | Hyperglycemia (Diabetes mellitus) |
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| HP:0000822 | Hypertension |
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| HP:0001712 | Left ventricular hypertrophy |
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## MONDO Disease Ontology
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MONDO integrates disease classifications from multiple sources:
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- OMIM (Mendelian diseases)
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- ORPHANET (rare diseases)
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- MeSH (medical subject headings)
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- SNOMED CT
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- DOID (Disease Ontology)
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- EFO (Experimental Factor Ontology)
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### Key MONDO IDs for Common Rare Diseases
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| MONDO ID | Disease | OMIM |
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|----------|---------|------|
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| MONDO:0007739 | Huntington disease | OMIM:143100 |
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| MONDO:0009061 | Cystic fibrosis | OMIM:219700 |
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| MONDO:0008608 | Down syndrome | OMIM:190685 |
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| MONDO:0019391 | Fragile X syndrome | OMIM:300624 |
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| MONDO:0010726 | Rett syndrome | OMIM:312750 |
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| MONDO:0014517 | Dravet syndrome | OMIM:607208 |
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| MONDO:0024522 | SCN1A-related epilepsy | — |
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| MONDO:0014817 | CHARGE syndrome | OMIM:214800 |
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| MONDO:0009764 | Marfan syndrome | OMIM:154700 |
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| MONDO:0013282 | Alpha-1-antitrypsin deficiency | OMIM:613490 |
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### OMIM ID Patterns
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- **Phenotype only**: OMIM number alone (e.g., OMIM:104300)
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- **Gene and phenotype**: Same gene, multiple phenotype entries
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- **Phenotype series**: Grouped phenotypes at a locus
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```python
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import requests
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def omim_to_mondo(omim_id):
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"""Convert OMIM ID to MONDO ID via Monarch API."""
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search_id = f"OMIM:{omim_id}" if not omim_id.startswith("OMIM:") else omim_id
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data = requests.get(
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f"https://api-v3.monarchinitiative.org/v3/entity/{search_id}"
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).json()
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# Check for same_as/equivalent_id links to MONDO
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return data
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```
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## Association Evidence Codes
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Monarch associations include evidence types:
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| Code | Evidence Type |
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|------|--------------|
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| `IEA` | Inferred from electronic annotation |
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| `TAS` | Traceable author statement |
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| `IMP` | Inferred from mutant phenotype |
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| `IGI` | Inferred from genetic interaction |
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| `IDA` | Inferred from direct assay |
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| `ISS` | Inferred from sequence or structural similarity |
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| `IBA` | Inferred from biological aspect of ancestor |
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Higher-quality evidence: IDA > TAS > IMP > IEA
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## Semantic Similarity Metrics
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Monarch supports multiple similarity metrics:
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| Metric | Description | Use case |
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|--------|-------------|---------|
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| `ancestor_information_content` | IC of most informative common ancestor (MICA) | Disease similarity |
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| `jaccard_similarity` | Overlap coefficient | Simple set comparison |
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| `cosine` | Cosine similarity of IC vectors | Large-scale comparisons |
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| `phenodigm` | Combined MICA + Jaccard | Model organism matching |
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```python
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import requests
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def compute_disease_similarity(disease_ids_1, disease_ids_2, metric="ancestor_information_content"):
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"""Compute semantic similarity between two sets of disease phenotypes."""
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# Get phenotype sets for each disease
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url = "https://api-v3.monarchinitiative.org/v3/semsim/compare"
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params = {
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"subjects": disease_ids_1,
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"objects": disease_ids_2,
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"metric": metric
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}
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response = requests.get(url, params=params)
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return response.json()
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```
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