@synsci/cli-darwin-x64-baseline 1.1.76 → 1.1.78

package/bin/skills/torchdrug/references/datasets.md

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+# Datasets Reference
+
+## Overview
+
+TorchDrug provides 40+ curated datasets across multiple domains: molecular property prediction, protein modeling, knowledge graph reasoning, and retrosynthesis. All datasets support lazy loading, automatic downloading, and customizable feature extraction.
+
+## Molecular Property Prediction Datasets
+
+### Drug Discovery Classification
+
+| Dataset | Size | Task | Classes | Description |
+|---------|------|------|---------|-------------|
+| **BACE** | 1,513 | Binary | 2 | β-secretase inhibition for Alzheimer's |
+| **BBBP** | 2,039 | Binary | 2 | Blood-brain barrier penetration |
+| **HIV** | 41,127 | Binary | 2 | Inhibition of HIV replication |
+| **ClinTox** | 1,478 | Multi-label | 2 | Clinical trial toxicity |
+| **SIDER** | 1,427 | Multi-label | 27 | Side effects by system organ class |
+| **Tox21** | 7,831 | Multi-label | 12 | Toxicity across 12 targets |
+| **ToxCast** | 8,576 | Multi-label | 617 | High-throughput toxicology |
+| **MUV** | 93,087 | Multi-label | 17 | Unbiased validation for screening |
+
+**Key Features:**
+- All use scaffold splits for realistic evaluation
+- Binary classification metrics: AUROC, AUPRC
+- Multi-label handles missing values
+
+**Use Cases:**
+- Drug safety prediction
+- Virtual screening
+- ADMET property prediction
+
+### Drug Discovery Regression
+
+| Dataset | Size | Property | Units | Description |
+|---------|------|----------|-------|-------------|
+| **ESOL** | 1,128 | Solubility | log(mol/L) | Water solubility |
+| **FreeSolv** | 642 | Hydration | kcal/mol | Hydration free energy |
+| **Lipophilicity** | 4,200 | LogD | - | Octanol/water distribution |
+| **SAMPL** | 643 | Solvation | kcal/mol | Solvation free energies |
+
+**Metrics:** MAE, RMSE, R²
+**Use Cases:** ADME optimization, lead optimization
+
+### Quantum Chemistry
+
+| Dataset | Size | Properties | Description |
+|---------|------|------------|-------------|
+| **QM7** | 7,165 | 1 | Atomization energy |
+| **QM8** | 21,786 | 12 | Electronic spectra, excited states |
+| **QM9** | 133,885 | 12 | Geometric, energetic, electronic, thermodynamic |
+| **PCQM4M** | 3.8M | 1 | Large-scale HOMO-LUMO gap |
+
+**Properties (QM9):**
+- Dipole moment
+- Isotropic polarizability
+- HOMO/LUMO energies
+- Internal energy, enthalpy, free energy
+- Heat capacity
+- Electronic spatial extent
+
+**Use Cases:**
+- Quantum property prediction
+- Method development benchmarking
+- Pre-training molecular models
+
+### Large Molecule Databases
+
+| Dataset | Size | Description | Use Case |
+|---------|------|-------------|----------|
+| **ZINC250k** | 250,000 | Drug-like molecules | Generative model training |
+| **ZINC2M** | 2,000,000 | Drug-like molecules | Large-scale pre-training |
+| **ChEMBL** | Millions | Bioactive molecules | Property prediction, generation |
+
+## Protein Datasets
+
+### Function Prediction
+
+| Dataset | Size | Task | Classes | Description |
+|---------|------|------|---------|-------------|
+| **EnzymeCommission** | 17,562 | Multi-class | 7 levels | EC number classification |
+| **GeneOntology** | 46,796 | Multi-label | 489 | GO term prediction (BP/MF/CC) |
+| **BetaLactamase** | 5,864 | Regression | - | Enzyme activity levels |
+| **Fluorescence** | 54,025 | Regression | - | GFP fluorescence intensity |
+| **Stability** | 53,614 | Regression | - | Thermostability (ΔΔG) |
+
+**Features:**
+- Sequence and/or structure input
+- Evolutionary information available
+- Multiple train/test splits
+
+**Use Cases:**
+- Protein engineering
+- Function annotation
+- Enzyme design
+
+### Localization and Solubility
+
+| Dataset | Size | Task | Classes | Description |
+|---------|------|------|---------|-------------|
+| **Solubility** | 62,478 | Binary | 2 | Protein solubility |
+| **BinaryLocalization** | 22,168 | Binary | 2 | Membrane vs soluble |
+| **SubcellularLocalization** | 8,943 | Multi-class | 10 | Subcellular compartment |
+
+**Use Cases:**
+- Protein expression optimization
+- Target identification
+- Cell biology
+
+### Structure Prediction
+
+| Dataset | Size | Task | Description |
+|---------|------|------|-------------|
+| **Fold** | 16,712 | Multi-class (1,195) | Structural fold recognition |
+| **SecondaryStructure** | 8,678 | Sequence labeling | 3-state or 8-state prediction |
+| **ProteinNet** | Varied | Contact prediction | Residue-residue contacts |
+
+**Use Cases:**
+- Structure prediction pipelines
+- Fold recognition
+- Contact map generation
+
+### Protein Interactions
+
+| Dataset | Size | Positives | Negatives | Description |
+|---------|------|-----------|-----------|-------------|
+| **HumanPPI** | 1,412 proteins | 6,584 | - | Human protein interactions |
+| **YeastPPI** | 2,018 proteins | 6,451 | - | Yeast protein interactions |
+| **PPIAffinity** | 2,156 pairs | - | - | Binding affinity values |
+
+**Use Cases:**
+- PPI prediction
+- Network biology
+- Drug target identification
+
+### Protein-Ligand Binding
+
+| Dataset | Size | Type | Description |
+|---------|------|------|-------------|
+| **BindingDB** | ~1.5M | Affinity | Comprehensive binding data |
+| **PDBBind** | 20,000+ | 3D complexes | Structure-based binding |
+| - Refined Set | 5,316 | High quality | Curated crystal structures |
+| - Core Set | 285 | Benchmark | Diverse test set |
+
+**Use Cases:**
+- Binding affinity prediction
+- Structure-based drug design
+- Scoring function development
+
+### Large Protein Databases
+
+| Dataset | Size | Description |
+|---------|------|-------------|
+| **AlphaFoldDB** | 200M+ | Predicted structures for most known proteins |
+| **UniProt** | Integration | Sequence and annotation data |
+
+## Knowledge Graph Datasets
+
+### General Knowledge
+
+| Dataset | Entities | Relations | Triples | Domain |
+|---------|----------|-----------|---------|--------|
+| **FB15k** | 14,951 | 1,345 | 592,213 | Freebase (general knowledge) |
+| **FB15k-237** | 14,541 | 237 | 310,116 | Filtered Freebase |
+| **WN18** | 40,943 | 18 | 151,442 | WordNet (lexical) |
+| **WN18RR** | 40,943 | 11 | 93,003 | Filtered WordNet |
+
+**Relation Types (FB15k-237):**
+- `/people/person/nationality`
+- `/film/film/genre`
+- `/location/location/contains`
+- `/business/company/founders`
+- Many more...
+
+**Use Cases:**
+- Link prediction
+- Relation extraction
+- Knowledge base completion
+
+### Biomedical Knowledge
+
+| Dataset | Entities | Relations | Triples | Description |
+|---------|----------|-----------|---------|-------------|
+| **Hetionet** | 45,158 | 24 | 2,250,197 | Integrates 29 biomedical databases |
+
+**Entity Types in Hetionet:**
+- Genes (20,945)
+- Compounds (1,552)
+- Diseases (137)
+- Anatomy (400)
+- Pathways (1,822)
+- Pharmacologic classes
+- Side effects
+- Symptoms
+- Molecular functions
+- Biological processes
+- Cellular components
+
+**Relation Types:**
+- Compound-binds-Gene
+- Gene-associates-Disease
+- Disease-presents-Symptom
+- Compound-treats-Disease
+- Compound-causes-Side effect
+- Gene-participates-Pathway
+- And 18 more...
+
+**Use Cases:**
+- Drug repurposing
+- Disease mechanism discovery
+- Target identification
+- Multi-hop reasoning in biomedicine
+
+## Citation Network Datasets
+
+| Dataset | Nodes | Edges | Classes | Description |
+|---------|-------|-------|---------|-------------|
+| **Cora** | 2,708 | 5,429 | 7 | Machine learning papers |
+| **CiteSeer** | 3,327 | 4,732 | 6 | Computer science papers |
+| **PubMed** | 19,717 | 44,338 | 3 | Biomedical papers |
+
+**Use Cases:**
+- Node classification
+- GNN baseline comparisons
+- Method development
+
+## Retrosynthesis Datasets
+
+| Dataset | Size | Description |
+|---------|------|-------------|
+| **USPTO-50k** | 50,017 | Curated patent reactions, single-step |
+
+**Features:**
+- Product → Reactants mapping
+- Atom mapping for reaction centers
+- Canonicalized SMILES
+- Balanced across reaction types
+
+**Splits:**
+- Train: ~40,000
+- Validation: ~5,000
+- Test: ~5,000
+
+**Use Cases:**
+- Retrosynthesis prediction
+- Reaction type classification
+- Synthetic route planning
+
+## Dataset Usage Patterns
+
+### Loading Datasets
+
+```python
+from torchdrug import datasets
+
+# Basic loading
+dataset = datasets.BBBP("~/molecule-datasets/")
+
+# With transforms
+from torchdrug import transforms
+transform = transforms.VirtualNode()
+dataset = datasets.BBBP("~/molecule-datasets/", transform=transform)
+
+# Protein dataset
+dataset = datasets.EnzymeCommission("~/protein-datasets/")
+
+# Knowledge graph
+dataset = datasets.FB15k237("~/kg-datasets/")
+```
+
+### Data Splitting
+
+```python
+# Random split
+train, valid, test = dataset.split([0.8, 0.1, 0.1])
+
+# Scaffold split (for molecules)
+from torchdrug import utils
+train, valid, test = dataset.split(
+    utils.scaffold_split(dataset, [0.8, 0.1, 0.1])
+)
+
+# Predefined splits (some datasets)
+train, valid, test = dataset.split()
+```
+
+### Feature Extraction
+
+**Node Features (Molecules):**
+- Atom type (one-hot or embedding)
+- Formal charge
+- Hybridization
+- Aromaticity
+- Number of hydrogens
+- Chirality
+
+**Edge Features (Molecules):**
+- Bond type (single, double, triple, aromatic)
+- Stereochemistry
+- Conjugation
+- Ring membership
+
+**Node Features (Proteins):**
+- Amino acid type (one-hot)
+- Physicochemical properties
+- Position in sequence
+- Secondary structure
+- Solvent accessibility
+
+**Edge Features (Proteins):**
+- Edge type (sequential, spatial, contact)
+- Distance
+- Angles and dihedrals
+
+## Choosing Datasets
+
+### By Task
+
+**Molecular Property Prediction:**
+- Start with BBBP or HIV (medium size, clear task)
+- Use QM9 for quantum properties
+- ESOL/FreeSolv for regression
+
+**Protein Function:**
+- EnzymeCommission (well-defined classes)
+- GeneOntology (comprehensive annotations)
+
+**Drug Safety:**
+- Tox21 (standard benchmark)
+- ClinTox (clinical relevance)
+
+**Structure-Based:**
+- PDBBind (protein-ligand)
+- ProteinNet (structure prediction)
+
+**Knowledge Graph:**
+- FB15k-237 (standard benchmark)
+- Hetionet (biomedical applications)
+
+**Generation:**
+- ZINC250k (training)
+- QM9 (with properties)
+
+**Retrosynthesis:**
+- USPTO-50k (only choice)
+
+### By Size and Resources
+
+**Small (<5k, for testing):**
+- BACE, FreeSolv, ClinTox
+- Core set of PDBBind
+
+**Medium (5k-100k):**
+- BBBP, HIV, ESOL, Tox21
+- EnzymeCommission, Fold
+- FB15k-237, WN18RR
+
+**Large (>100k):**
+- QM9, MUV, PCQM4M
+- GeneOntology, AlphaFoldDB
+- ZINC2M, BindingDB
+
+### By Domain
+
+**Drug Discovery:** BBBP, HIV, Tox21, ESOL, ZINC
+**Quantum Chemistry:** QM7, QM8, QM9, PCQM4M
+**Protein Engineering:** Fluorescence, Stability, Solubility
+**Structural Biology:** Fold, PDBBind, ProteinNet, AlphaFoldDB
+**Biomedical:** Hetionet, GeneOntology, EnzymeCommission
+**Retrosynthesis:** USPTO-50k
+
+## Best Practices
+
+1. **Start Small**: Test on small datasets before scaling
+2. **Scaffold Split**: Use for realistic drug discovery evaluation
+3. **Balanced Metrics**: Use AUROC + AUPRC for imbalanced data
+4. **Multiple Runs**: Report mean ± std over multiple random seeds
+5. **Data Leakage**: Be careful with pre-trained models
+6. **Domain Knowledge**: Understand what you're predicting
+7. **Validation**: Always use held-out test set
+8. **Preprocessing**: Standardize features, handle missing values

package/bin/skills/torchdrug/references/knowledge_graphs.md

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+# Knowledge Graph Reasoning
+
+## Overview
+
+Knowledge graphs represent structured information as entities and relations in a graph format. TorchDrug provides comprehensive support for knowledge graph completion (link prediction) using embedding-based models and neural reasoning approaches.
+
+## Available Datasets
+
+### General Knowledge Graphs
+
+**FB15k (Freebase subset):**
+- 14,951 entities
+- 1,345 relation types
+- 592,213 triples
+- General world knowledge from Freebase
+
+**FB15k-237:**
+- 14,541 entities
+- 237 relation types
+- 310,116 triples
+- Filtered version removing inverse relations
+- More challenging benchmark
+
+**WN18 (WordNet):**
+- 40,943 entities (word senses)
+- 18 relation types (lexical relations)
+- 151,442 triples
+- Linguistic knowledge graph
+
+**WN18RR:**
+- 40,943 entities
+- 11 relation types
+- 93,003 triples
+- Filtered WordNet removing easy inverse patterns
+
+### Biomedical Knowledge Graphs
+
+**Hetionet:**
+- 45,158 entities (genes, compounds, diseases, pathways, etc.)
+- 24 relation types (treats, causes, binds, etc.)
+- 2,250,197 edges
+- Integrates 29 public biomedical databases
+- Designed for drug repurposing and disease understanding
+
+## Task: KnowledgeGraphCompletion
+
+The primary task for knowledge graphs is link prediction - given a head entity and relation, predict the tail entity (or vice versa).
+
+### Task Modes
+
+**Head Prediction:**
+- Given (?, relation, tail), predict head entity
+- "What can cause Disease X?"
+
+**Tail Prediction:**
+- Given (head, relation, ?), predict tail entity
+- "What diseases does Gene X cause?"
+
+**Both:**
+- Predict both head and tail
+- Standard evaluation protocol
+
+### Evaluation Metrics
+
+**Ranking Metrics:**
+- **Mean Rank (MR)**: Average rank of correct entity
+- **Mean Reciprocal Rank (MRR)**: Average of 1/rank
+- **Hits@K**: Percentage of correct entities in top K predictions
+  - Typically reported for K=1, 3, 10
+
+**Filtered vs Raw:**
+- **Filtered**: Remove other known true triples from ranking
+- **Raw**: Rank among all possible entities
+- Filtered is standard for evaluation
+
+## Embedding Models
+
+### Translational Models
+
+**TransE (Translation Embedding):**
+- Represents relations as translations in embedding space
+- h + r ≈ t (head + relation ≈ tail)
+- Simple and effective baseline
+- Works well for 1-to-1 relations
+- Struggles with N-to-N relations
+
+**RotatE (Rotation Embedding):**
+- Relations as rotations in complex space
+- Better handles symmetric and inverse relations
+- State-of-the-art on many benchmarks
+- Can model composition patterns
+
+### Semantic Matching Models
+
+**DistMult:**
+- Bilinear scoring function
+- Handles symmetric relations naturally
+- Cannot model asymmetric relations
+- Fast and memory efficient
+
+**ComplEx:**
+- Complex-valued embeddings
+- Models asymmetric and inverse relations
+- Better than DistMult for most graphs
+- Balances expressiveness and efficiency
+
+**SimplE:**
+- Extends DistMult with inverse relations
+- Fully expressive (can represent any relation pattern)
+- Two embeddings per entity (canonical and inverse)
+
+### Neural Logic Models
+
+**NeuralLP (Neural Logic Programming):**
+- Learns logical rules through differentiable operations
+- Interprets predictions via learned rules
+- Good for sparse knowledge graphs
+- Computationally more expensive
+
+**KBGAT (Knowledge Base Graph Attention):**
+- Graph attention networks for KG completion
+- Learns entity representations from neighborhood
+- Handles unseen entities through inductive learning
+- Better for incomplete graphs
+
+## Training Workflow
+
+### Basic Pipeline
+
+```python
+from torchdrug import datasets, models, tasks, core
+
+# Load dataset
+dataset = datasets.FB15k237("~/kg-datasets/")
+
+# Define model
+model = models.RotatE(
+    num_entity=dataset.num_entity,
+    num_relation=dataset.num_relation,
+    embedding_dim=2000,
+    max_score=9
+)
+
+# Define task
+task = tasks.KnowledgeGraphCompletion(
+    model,
+    num_negative=128,
+    adversarial_temperature=2,
+    criterion="bce"
+)
+
+# Train with PyTorch Lightning or custom loop
+```
+
+### Negative Sampling
+
+**Strategies:**
+- **Uniform**: Sample entities uniformly at random
+- **Self-Adversarial**: Weight samples by current model's scores
+- **Type-Constrained**: Sample only valid entity types for relation
+
+**Parameters:**
+- `num_negative`: Number of negative samples per positive triple
+- `adversarial_temperature`: Temperature for self-adversarial weighting
+- Higher temperature = more focus on hard negatives
+
+### Loss Functions
+
+**Binary Cross-Entropy (BCE):**
+- Treats each triple independently
+- Balanced classification between positive and negative
+
+**Margin Loss:**
+- Ensures positive scores higher than negative by margin
+- `max(0, margin + score_neg - score_pos)`
+
+**Logistic Loss:**
+- Smooth version of margin loss
+- Better gradient properties
+
+## Model Selection Guide
+
+### By Relation Patterns
+
+**1-to-1 Relations:**
+- TransE works well
+- Any model will likely succeed
+
+**1-to-N Relations:**
+- DistMult, ComplEx, SimplE
+- Avoid TransE
+
+**N-to-1 Relations:**
+- DistMult, ComplEx, SimplE
+- Avoid TransE
+
+**N-to-N Relations:**
+- ComplEx, SimplE, RotatE
+- Most challenging pattern
+
+**Symmetric Relations:**
+- DistMult, ComplEx
+- RotatE with proper initialization
+
+**Antisymmetric Relations:**
+- ComplEx, SimplE, RotatE
+- Avoid DistMult
+
+**Inverse Relations:**
+- ComplEx, SimplE, RotatE
+- Important for bidirectional reasoning
+
+**Composition:**
+- RotatE (best)
+- TransE (reasonable)
+- Captures multi-hop paths
+
+### By Dataset Characteristics
+
+**Small Graphs (< 50k entities):**
+- ComplEx or SimplE
+- Lower embedding dimensions (200-500)
+
+**Large Graphs (> 100k entities):**
+- DistMult for efficiency
+- RotatE for accuracy
+- Higher dimensions (500-2000)
+
+**Sparse Graphs:**
+- NeuralLP (learns rules from limited data)
+- Pre-train embeddings on larger graphs
+
+**Dense, Complete Graphs:**
+- Any embedding model works well
+- Choose based on relation patterns
+
+**Biomedical/Domain Graphs:**
+- Consider type constraints in sampling
+- Use domain-specific negative sampling
+- Hetionet benefits from relation-specific models
+
+## Advanced Techniques
+
+### Multi-Hop Reasoning
+
+Chain multiple relations to answer complex queries:
+- "What drugs treat diseases caused by gene X?"
+- Requires path-based or rule-based reasoning
+- NeuralLP naturally supports this
+
+### Temporal Knowledge Graphs
+
+Extend to time-varying facts:
+- Add temporal information to triples
+- Predict future facts
+- Requires temporal encoding in models
+
+### Few-Shot Learning
+
+Handle relations with few examples:
+- Meta-learning approaches
+- Transfer from related relations
+- Important for emerging knowledge
+
+### Inductive Learning
+
+Generalize to unseen entities:
+- KBGAT and other GNN-based methods
+- Use entity features/descriptions
+- Critical for evolving knowledge graphs
+
+## Biomedical Applications
+
+### Drug Repurposing
+
+Predict "drug treats disease" links in Hetionet:
+1. Train on known drug-disease associations
+2. Predict new treatment candidates
+3. Filter by mechanism (gene, pathway involvement)
+4. Validate predictions experimentally
+
+### Disease Gene Discovery
+
+Identify genes associated with diseases:
+1. Model gene-disease-pathway networks
+2. Predict missing gene-disease links
+3. Incorporate protein interactions, expression data
+4. Prioritize candidates for validation
+
+### Protein Function Prediction
+
+Link proteins to biological processes:
+1. Integrate protein interactions, GO terms
+2. Predict missing GO annotations
+3. Transfer function from similar proteins
+
+## Common Issues and Solutions
+
+**Issue: Poor performance on specific relation types**
+- Solution: Analyze relation patterns, choose appropriate model, or use relation-specific models
+
+**Issue: Overfitting on small graphs**
+- Solution: Reduce embedding dimension, increase regularization, or use simpler models
+
+**Issue: Slow training on large graphs**
+- Solution: Reduce negative samples, use DistMult for efficiency, or implement mini-batch training
+
+**Issue: Cannot handle new entities**
+- Solution: Use inductive models (KBGAT), incorporate entity features, or pre-compute embeddings for new entities based on their neighbors
+
+## Best Practices
+
+1. Start with ComplEx or RotatE for most tasks
+2. Use self-adversarial negative sampling
+3. Tune embedding dimension (typically 500-2000)
+4. Apply regularization to prevent overfitting
+5. Use filtered evaluation metrics
+6. Analyze performance per relation type
+7. Consider relation-specific models for heterogeneous graphs
+8. Validate predictions with domain experts