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Learning the natural history of human disease with generative transformers

Authors: Artem Shmatko*, Alexander Wolfgang Jung*, Kumar Gaurav*, Søren Brunak, Laust Mortensen, Ewan Birney, Tom Fitzgerald, Moritz Gerstung (*Equal Contribution)

Overview

This repository contains the code for Delphi, a modified GPT-2 model designed to learn the natural history of human disease using generative transformers. The implementation is based on Andrej Karpathy's nanoGPT and includes training code and analysis notebooks.

Installation

Option 1: Conda Environment

1. Clone the repository:

   git clone https://github.com/gerstung-lab/Delphi.git
   cd Delphi
   

2. Create and activate the conda environment:

   conda create -n delphi python=3.11
   conda activate delphi
   pip install -r requirements.txt
   

   Note: Installing requirements typically takes a few minutes.

Option 2: Docker

We provide a Dockerfile for containerized training and downstream analyses. See containers/Dockerfile for implementation details.

Data

UK Biobank Access

Delphi-2M is trained on 500K patient health trajectories from the UK Biobank dataset. Access to this data requires a research application through the UK Biobank.

Data Preparation

For detailed instructions on preparing training data, please refer to data/README.md.

Configuration and Training

Prerequisites

Set the following environment variables:

• DELPHI_DATA_DIR: Directory containing training and validation data
• DELPHI_CKPT_DIR: Directory for storing model checkpoints

Tip: We recommend using a .env file with direnv for environment management.

Training

Delphi uses OmegaConf for experiment configuration management. Here's an example configuration:

# example.yaml
ckpt_dir: example # Saves to $DELPHI_CKPT_DIR/example
eval_interval: 25
eval_iters: 25
eval_only: false
init_from: scratch
seed: 42
gradient_accumulation_steps: 1
batch_size: 128
device: cuda # Options: cuda, cpu, mps

# Training data configuration
infer_train_biomarkers: true
train_data:
  data_dir: ukb_real_data # Loads from $DELPHI_DATA_DIR/ukb_real_data
  subject_list: ukb_real_data/participants/train_fold.bin
  seed: 42
  biomarker_dir: ukb_real_data/biomarkers
  expansion_pack_dir: ukb_real_data/expansion_packs
  expansion_packs:
    - prescriptions
    - summary_ops
  transforms:
    - name: no-event
      args:
        interval_in_years: 5
        mode: random

# Validation data configuration
infer_val_biomarkers: true
infer_val_expansion_packs: true
val_data:
  data_dir: ukb_real_data
  subject_list: ukb_real_data/participants/val_fold.bin
  seed: 42
  biomarker_dir: ukb_real_data/biomarkers
  expansion_pack_dir: ukb_real_data/expansion_packs
  transforms:
    - name: no-event
      args:
        interval_in_years: 5
        mode: random

ignore_expansion_tokens: true

# Model architecture
model:
  n_layer: 12
  n_head: 12
  n_embd: 120
  dropout: 0.1
  token_dropout: 0.0
  t_min: 0.1
  bias: true
  mask_ties: true
  ignore_tokens:
    - padding
    - male
    - female
    - config/disease_list/lifestyle.yaml
  biomarkers:
    prs:
      projector: linear
      input_size: 36
    wbc:
      projector: linear
      input_size: 31
  modality_emb: true
  loss:
    ce_beta: 1.0
    dt_beta: 1.0

# Logging configuration
log:
  wandb_log: true
  wandb_project: ${ckpt_dir}
  run_name: example
  log_interval: 25
  always_ckpt_after_eval: true
  ckpt_interval: null

# Optimization settings
optim:
  learning_rate: 6e-4
  max_iters: 100000
  weight_decay: 2e-1
  lr_decay_iters: 100000
  min_lr: 6e-5
  beta2: 0.99
  warmup_iters: 1000

Execute the following command to start training:

python train.py config=example.yaml
# Override specific parameters: python train.py config=example.yaml device=cuda

Evaluation

The currently supported evaluation tasks are:

• AUC per disease stratified by age and sex

Stratified AUC

First, do a forward pass to get the logits from the model:

python apps/forward.py config=config/forward.yaml ckpt=$MODEL_CHECKPOINT

The configuration file for the forward pass is structured like this:

# forward.yaml
name: forward # name of directory where outputs will be written to
device: cuda
batch_size: 128
subsample: null
use_val_data: true # True if you want to use the same data configuration as the validation fold during model training
data: # data configuration; ignored if use_val_data is set to True
  data_dir: ukb_real_data
  subject_list: ukb_real_data/participants/val_fold.bin
  seed: 42
  transforms:
    - name: no-event
      args:
        interval_in_years: 5
        mode: random
log:
  save_tokens: true
  save_logits: true
  flush_interval: 10 # higher interval -> faster but more RAM usage
  wandb_log: false

Next, run the following command to launch the eval task:

python apps/eval.py config=config/eval/auc.yaml ckpt=$MODEL_CHECKPOINT

The configuration file for this eval task is structured like this:

# auc.yaml
task_name: auc_eval_task
task_type: auc
task_input: forward
task_args:
  disease_lst: config/disease_list/doi.yaml # path to a list of diseases to evaluate on; some lists are provided at config/disease_list
  min_time_gap: 0.1
  age_groups:
    bin_start: 40
    bin_end: 80
    bin_width: 5
  event_input_only: false

Development

Code Quality

This project uses pre-commit hooks to maintain code quality standards.

Setup Pre-commit Hooks

1. Install pre-commit (if not already available):

   # Via conda (recommended for base environment)
   conda install pre-commit
   # Or via Homebrew
   brew install pre-commit
   

2. Install hooks in your local repository:

   # From project root directory
   pre-commit install --install-hooks
   

3. Manual execution (optional):

   pre-commit run --all-files
   

Citation

If you use this work, please cite our paper:

@article{Shmatko2024.06.07.24308553,
    title = {Learning the natural history of human disease with generative transformers},
    author = {Shmatko, Artem and Jung, Alexander Wolfgang and Gaurav, Kumar and Brunak, S{\o}ren and Mortensen, Laust and Birney, Ewan and Fitzgerald, Tom and Gerstung, Moritz},
    doi = {10.1101/2024.06.07.24308553},
    journal = {medRxiv},
    publisher = {Cold Spring Harbor Laboratory Press},
    year = {2024}
}

License

This project is licensed under the MIT License - see the badge above for details.