Cheminformatics Clustering

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Introduction

A central task in drug discovery is searching, screening, and organizing large chemical databases. Here, we implement clustering on molecular similarity. We support multiple methods to provide a interactive exploration of chemical space.

• Compute Morgan circular fingerprints, cluster using k-means, and perform dimensionality reduction using PCA and UMAP. Distributed GPU-accelerated algorithms with multi-GPU support are used in this method. This allows processing very large datasets.
• Compute Morgan circular fingerprints, Sparse Random Projection and cluster using k-means.
• Generate new molecules either by exploring the latent space between two molecules or sampling around a molecule

Preparing the Environment (optional)

A launch script, launch.sh, is provided to perform all tasks.

Customization

The environment can be customized for control of the container, to create your own repo, or to store the data in a custom location. However, if this is not needed, skip to Getting Started to use the defaults.

To customize your local environment, edit the appropriate section of launch.sh or provide a ~/.env file with the following information below. To generate a template for .env, just run ./launch.sh with no arguments. If .env does not exist, then a template will be written for you.

CUCHEM_CONT=nvcr.io/nvstaging/clara/cheminformatics_demo:latest
MEGAMOLBART_CONT=nvcr.io/nvstaging/clara/megamolbart:latest
MEGAMOLBART_MODEL=nvstaging/clara/megamolbart:0.1
PROJECT_PATH=/home/user_home/code/cheminformatics
CONTENT_PATH=/home/user_home/data
DATA_MOUNT_PATH=/data
PLOTLY_PORT=5000
DASK_PORT=9001
SUBNET=192.177.100.0/16
IP_CUCHEM_UI=192.177.100.1
IP_MEGAMOLBART=192.177.100.2
REGISTRY=nvcr.io
REGISTRY_USER='$oauthtoken'
REGISTRY_ACCESS_TOKEN=<<NGC KEY from https://ngc.nvidia.com/setup/api-key>>

Getting Started

Please install NGC CLI from https://ngc.nvidia.com/setup/installers/cli. And obtain a NGC Key from https://ngc.nvidia.com/setup/api-key.

Once your environment is setup, the following commands should be all you need.

Build your container:

./launch.sh build

Download the ChEMBL database (version 27):

./launch.sh dbSetup

Launch the interactive ChEMBL exploration tool:

./launch.sh start

optional arguments:
  -h, --help            show this help message and exit
  --cpu                 Use CPU
  -b, --benchmark       Execute for benchmark
  -p PCA_COMPS, --pca_comps PCA_COMPS
                        Number of PCA components
  -n NUM_CLUSTERS, --num_clusters NUM_CLUSTERS
                        Numer of clusters
  -c CACHE_DIRECTORY, --cache_directory CACHE_DIRECTORY
                        Location to pick fingerprint from
  -m N_MOL, --n_mol N_MOL
                        Number of molecules for analysis. Use negative numbers
                        for using the whole dataset.
  --batch_size BATCH_SIZE
                        Chunksize.
  -o OUTPUT_DIR, --output_dir OUTPUT_DIR
                        Output directory for benchmark results
  --n_gpu N_GPU         Number of GPUs to use
  --n_cpu N_CPU         Number of CPU workers to use
  -d, --debug           Show debug message

Navigate a browser to:

https://0.0.0.0:5000

Tutorial

See the tutorial for an example walkthrough.

Advanced Setup

Caching Fingerprints

Users can generate Morgan Fingerprints and store it in HDF5 files for later use. Please use the following command to generate fingerprint cache.

./launch.sh cache -c /data/fp

It is best to create the cache at DATA_MOUNT_PATH property defined in ~/.env. Default value of this property is /data/. This is a mounted volumne from host and available for reuse beyond the container's lifetime.

Once generated, the cached fingerprints can be used for analysis using -c option.

./launch.sh start -c /data/fp

Conda

Conda environment support is available for user wanting to use the tool outside of containers. Please find the setup file in setup directory.

Acceleration

The latest benchmarks reside in the benchmark directory.

Benchmark tests run on A100:

• markdown
• Excel
• plot

Benchmark tests run on V100:

• markdown
• Excel
• plot

Features

• Cluster molecules from ChEMBL using the embedding generated from Morgan Fingerprints --> PCA --> UMAP
• Ability to color the clustered molecules based on molecular properties
• Ability to recluster on user selected subsets of molecules or specific clusters
• Designate and track molecules of interest during the analysis
• Generate new molecules by linearly interpolating the latent space between two selected molecules or sampling arround a selected molecule
• Export generated molecules in SDF format