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