Dataset Information

Semi-supervised Hierarchical Drug Embedding in Hyperbolic Space.

ABSTRACT: Learning accurate drug representations is essential for tasks such as computational drug repositioning and prediction of drug side effects. A drug hierarchy is a valuable source that encodes knowledge of relations among drugs in a tree-like structure where drugs that act on the same organs, treat the same disease, or bind to the same biological target are grouped together. However, its utility in learning drug representations has not yet been explored, and currently described drug representations cannot place novel molecules in a drug hierarchy. Here, we develop a semi-supervised drug embedding that incorporates two sources of information: (1) underlying chemical grammar that is inferred from chemical structures of drugs and drug-like molecules (unsupervised) and (2) hierarchical relations that are encoded in an expert-crafted hierarchy of approved drugs (supervised). We use the Variational Auto-Encoder (VAE) framework to encode the chemical structures of molecules and use the drug-drug similarity information obtained from the hierarchy to induce the clustering of drugs in hyperbolic space. The hyperbolic space is amenable for encoding hierarchical relations. Both quantitative and qualitative results support that the learned drug embedding can accurately reproduce the chemical structure and recapitulate the hierarchical relations among drugs. Furthermore, our approach can infer the pharmacological properties of novel molecules by retrieving similar drugs from the embedding space. We demonstrate that our drug embedding can predict new uses and discover new side effects of existing drugs. We show that it significantly outperforms comparison methods in both tasks.

SUBMITTER: Yu K

PROVIDER: S-EPMC7943198 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Semi-supervised Hierarchical Drug Embedding in Hyperbolic Space.

Yu Ke K Visweswaran Shyam S Batmanghelich Kayhan K

Journal of chemical information and modeling 20201103 12

Learning accurate drug representations is essential for tasks such as computational drug repositioning and prediction of drug side effects. A drug hierarchy is a valuable source that encodes knowledge of relations among drugs in a tree-like structure where drugs that act on the same organs, treat the same disease, or bind to the same biological target are grouped together. However, its utility in learning drug representations has not yet been explored, and currently described drug representation ...[more]

PMID: 33140969

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Project description:Hierarchical clustering (HC) is one of the most frequently used methods in computational biology in the analysis of high-dimensional genomics data. Given a data set, HC outputs a binary tree leaves of which are the data points and internal nodes represent clusters of various sizes. Normally, a fixed-height cut on the HC tree is chosen, and each contiguous branch of data points below that height is considered as a separate cluster. However, the fixed-height branch cut may not be ideal in situations where one expects a complicated tree structure with nested clusters. Furthermore, due to lack of utilization of related background information in selecting the cutoff, induced clusters are often difficult to interpret. This paper describes a novel procedure that aims to automatically extract meaningful clusters from the HC tree in a semi-supervised way. The procedure is implemented in the R package HCsnip available from Bioconductor. Rather than cutting the HC tree at a fixed-height, HCsnip probes the various way of snipping, possibly at variable heights, to tease out hidden clusters ensconced deep down in the tree. The cluster extraction process utilizes, along with the data set from which the HC tree is derived, commonly available background information. Consequently, the extracted clusters are highly reproducible and robust against various sources of variations that "haunted" high-dimensional genomics data. Since the clustering process is guided by the background information, clusters are easy to interpret. Unlike existing packages, no constraint is placed on the data type on which clustering is desired. Particularly, the package accepts patient follow-up data for guiding the cluster extraction process. To our knowledge, HCsnip is the first package that is able to decomposes the HC tree into clusters with piecewise snipping under the guidance of patient time-to-event information. Our implementation of the semi-supervised HC tree snipping framework is generic, and can be combined with other algorithms that operate on detected clusters.

Dataset Information

Semi-supervised Hierarchical Drug Embedding in Hyperbolic Space.

Publications

Semi-supervised Hierarchical Drug Embedding in Hyperbolic Space.

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