Getting Started

Welcome to THEMAP! This guide will help you get up and running with task hardness estimation for molecular activity prediction.

What is THEMAP?

THEMAP (Task Hardness Estimation for Molecular Activity Prediction) is a Python library designed to aid drug discovery by providing powerful methods for estimating the difficulty of bioactivity prediction tasks. It enables researchers to:

• Compute distances between molecular datasets using various metrics (OTDD, Euclidean, Cosine)
• Analyze protein similarity through sequence and structural features
• Estimate task hardness for transfer learning scenarios
• Build transferability maps for bioactivity prediction tasks
• Integrate multi-modal data (molecules, proteins, metadata)

Installation

Prerequisites

• Python 3.10 or higher
• conda (recommended) or pip

Basic Installation

# Clone the repository
git clone https://github.com/HFooladi/THEMAP.git
cd THEMAP

# Create and activate conda environment
conda env create -f environment.yml
conda activate themap

# Install THEMAP
pip install --no-deps -e .

Installation with Optional Dependencies

THEMAP has several optional dependency groups for different functionality:

# For basic molecular analysis
pip install -e ".[ml]"

# For protein analysis
pip install -e ".[protein]"

# For OTDD distance computation
pip install -e ".[otdd]"

# For all features
pip install -e ".[all]"

# For development
pip install -e ".[dev,test]"

Verify Installation

import themap
print(f"THEMAP version: {themap.__version__}")

# Test basic functionality
from themap.data import MoleculeDataset
from themap.distance import MoleculeDatasetDistance
print("✅ Installation successful!")

Quick Start

1. Molecular Dataset Distance

Compute distances between molecular datasets to understand chemical space similarity:

import os
from dpu_utils.utils.richpath import RichPath
from themap.data import MoleculeDataset
from themap.distance import MoleculeDatasetDistance

# Load datasets
source_path = RichPath.create("datasets/train/CHEMBL1023359.jsonl.gz")
target_path = RichPath.create("datasets/test/CHEMBL2219358.jsonl.gz")

source_dataset = MoleculeDataset.load_from_file(source_path)
target_dataset = MoleculeDataset.load_from_file(target_path)

# Compute distance using OTDD
distance_calc = MoleculeDatasetDistance(
    tasks=None,  # Will be auto-extracted from datasets
    molecule_method="otdd"
)

distances = distance_calc.get_distance()
print(distances)
# Output: {'CHEMBL2219358': {'CHEMBL1023359': 7.074298858642578}}

2. Protein Dataset Distance

Analyze protein similarity using sequence features:

from themap.data import ProteinDataset
from themap.distance import ProteinDatasetDistance

# Load protein datasets
source_proteins = ProteinDataset.load_from_file("datasets/train/train_proteins.fasta")
target_proteins = ProteinDataset.load_from_file("datasets/test/test_proteins.fasta")

# Compute euclidean distance between protein features
protein_distance = ProteinDatasetDistance(
    tasks=None,  # Will be auto-extracted
    protein_method="euclidean"
)

distances = protein_distance.get_distance()
print(distances)

3. Unified Task Analysis

Work with the unified task system that integrates multiple data modalities:

from themap.data.tasks import Tasks
from themap.distance import TaskDistance

# Load integrated tasks
tasks = Tasks.from_directory(
    directory="datasets/",
    task_list_file="datasets/sample_tasks_list.json",
    load_molecules=True,
    load_proteins=True,
    load_metadata=True,
    cache_dir="cache/"
)

print(f"Loaded {len(tasks)} tasks")
print(f"Train tasks: {tasks.get_num_fold_tasks('TRAIN')}")
print(f"Test tasks: {tasks.get_num_fold_tasks('TEST')}")

# Compute combined distances
task_distance = TaskDistance(
    tasks=tasks,
    molecule_method="cosine",
    protein_method="euclidean"
)

# Get all distance types
all_distances = task_distance.compute_all_distances()

Core Concepts

Tasks and Data Modalities

THEMAP organizes data around the concept of Tasks - individual bioactivity prediction problems that can contain:

• Molecular data: SMILES strings, molecular descriptors, embeddings
• Protein data: Sequences, structural features, embeddings
• Metadata: Assay descriptions, experimental conditions, bioactivity values

Distance Metrics

Different distance metrics are optimized for different scenarios:

Method	Use Case	Pros	Cons
OTDD	Comprehensive dataset comparison	Most accurate, considers both features and labels	Computationally expensive
Euclidean	Fast similarity estimation	Fast, interpretable	May miss complex relationships
Cosine	Feature orientation comparison	Good for high-dimensional data	Ignores magnitude differences

Task Hardness

Task hardness quantifies how difficult a prediction task is, which helps in:

• Transfer learning: Identify similar tasks for knowledge transfer
• Model selection: Choose appropriate models based on task complexity
• Resource allocation: Prioritize difficult tasks for more computational resources

Directory Structure

Understanding the expected directory structure helps organize your data:

your_project/
├── datasets/
│   ├── train/
│   │   ├── CHEMBL123.jsonl.gz    # Molecular data
│   │   ├── CHEMBL123.fasta       # Protein sequences
│   │   └── ...
│   ├── test/
│   │   └── ...
│   ├── valid/
│   │   └── ...
│   └── sample_tasks_list.json    # Task configuration
├── cache/                        # Feature caching
└── results/                      # Output analyses

Sample Task List Format

{
  "train": ["CHEMBL1023359", "CHEMBL1613776", ...],
  "test": ["CHEMBL2219358", "CHEMBL1963831", ...],
  "valid": ["CHEMBL2219236", ...]
}

Next Steps

Now that you have the basics:

1. Explore the tutorials: Check out detailed tutorials for step-by-step examples
2. Explore the code: Understand the codebase structure for advanced usage
3. Run the examples: Execute the provided example scripts
4. Join the community: Contribute to the project on GitHub

Common Issues

Import Errors

If you encounter import errors:

# Check if optional dependencies are installed
try:
    from themap.distance import MoleculeDatasetDistance
    print("✅ Distance module available")
except ImportError as e:
    print(f"❌ Missing dependencies: {e}")
    print("Install with: pip install -e '.[otdd]'")

Memory Issues

For large datasets:

# Reduce memory usage
distance_calc = MoleculeDatasetDistance(
    tasks=tasks,
    molecule_method="euclidean"  # Use instead of OTDD for large datasets
)

# Or limit OTDD samples
hopts = {"maxsamples": 500}  # Default is 1000

Data Format Issues

Ensure your data follows the expected format:

# Validate molecular data
dataset = MoleculeDataset.load_from_file("your_data.jsonl.gz")
print(f"Dataset contains {len(dataset)} molecules")
print(f"Sample molecule: {dataset[0].smiles}")

# Validate protein data
proteins = ProteinDataset.load_from_file("proteins.fasta")
print(f"Loaded {len(proteins)} protein sequences")

Ready to dive deeper? Continue with our comprehensive tutorials!