Dataset Information

SumGNN: multi-typed drug interaction prediction via efficient knowledge graph summarization.

ABSTRACT:

Motivation

Thanks to the increasing availability of drug-drug interactions (DDI) datasets and large biomedical knowledge graphs (KGs), accurate detection of adverse DDI using machine learning models becomes possible. However, it remains largely an open problem how to effectively utilize large and noisy biomedical KG for DDI detection. Due to its sheer size and amount of noise in KGs, it is often less beneficial to directly integrate KGs with other smaller but higher quality data (e.g. experimental data). Most of existing approaches ignore KGs altogether. Some tries to directly integrate KGs with other data via graph neural networks with limited success. Furthermore most previous works focus on binary DDI prediction whereas the multi-typed DDI pharmacological effect prediction is more meaningful but harder task.

Results

To fill the gaps, we propose a new method SumGNN: knowledge summarization graph neural network, which is enabled by a subgraph extraction module that can efficiently anchor on relevant subgraphs from a KG, a self-attention based subgraph summarization scheme to generate reasoning path within the subgraph, and a multi-channel knowledge and data integration module that utilizes massive external biomedical knowledge for significantly improved multi-typed DDI predictions. SumGNN outperforms the best baseline by up to 5.54%, and performance gain is particularly significant in low data relation types. In addition, SumGNN provides interpretable prediction via the generated reasoning paths for each prediction.

Availability and implementation

The code is available in Supplementary Material.

Supplementary information

Supplementary data are available at Bioinformatics online.

SUBMITTER: Yu Y

PROVIDER: S-EPMC10060701 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

SumGNN: multi-typed drug interaction prediction via efficient knowledge graph summarization.

Yu Yue Y Huang Kexin K Zhang Chao C Glass Lucas M LM Sun Jimeng J Xiao Cao C

Bioinformatics (Oxford, England) 20210901 18

<h4>Motivation</h4>Thanks to the increasing availability of drug-drug interactions (DDI) datasets and large biomedical knowledge graphs (KGs), accurate detection of adverse DDI using machine learning models becomes possible. However, it remains largely an open problem how to effectively utilize large and noisy biomedical KG for DDI detection. Due to its sheer size and amount of noise in KGs, it is often less beneficial to directly integrate KGs with other smaller but higher quality data (e.g. ex ...[more]

PMID: 33769494

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Project description:BackgroundCurrent approaches to identifying drug-drug interactions (DDIs), include safety studies during drug development and post-marketing surveillance after approval, offer important opportunities to identify potential safety issues, but are unable to provide complete set of all possible DDIs. Thus, the drug discovery researchers and healthcare professionals might not be fully aware of potentially dangerous DDIs. Predicting potential drug-drug interaction helps reduce unanticipated drug interactions and drug development costs and optimizes the drug design process. Methods for prediction of DDIs have the tendency to report high accuracy but still have little impact on translational research due to systematic biases induced by networked/paired data. In this work, we aimed to present realistic evaluation settings to predict DDIs using knowledge graph embeddings. We propose a simple disjoint cross-validation scheme to evaluate drug-drug interaction predictions for the scenarios where the drugs have no known DDIs.ResultsWe designed different evaluation settings to accurately assess the performance for predicting DDIs. The settings for disjoint cross-validation produced lower performance scores, as expected, but still were good at predicting the drug interactions. We have applied Logistic Regression, Naive Bayes and Random Forest on DrugBank knowledge graph with the 10-fold traditional cross validation using RDF2Vec, TransE and TransD. RDF2Vec with Skip-Gram generally surpasses other embedding methods. We also tested RDF2Vec on various drug knowledge graphs such as DrugBank, PharmGKB and KEGG to predict unknown drug-drug interactions. The performance was not enhanced significantly when an integrated knowledge graph including these three datasets was used.ConclusionWe showed that the knowledge embeddings are powerful predictors and comparable to current state-of-the-art methods for inferring new DDIs. We addressed the evaluation biases by introducing drug-wise and pairwise disjoint test classes. Although the performance scores for drug-wise and pairwise disjoint seem to be low, the results can be considered to be realistic in predicting the interactions for drugs with limited interaction information.

Project description:BackgroundThe pharmaceutical field faces a significant challenge in validating drug target interactions (DTIs) due to the time and cost involved, leading to only a fraction being experimentally verified. To expedite drug discovery, accurate computational methods are essential for predicting potential interactions. Recently, machine learning techniques, particularly graph-based methods, have gained prominence. These methods utilize networks of drugs and targets, employing knowledge graph embedding (KGE) to represent structured information from knowledge graphs in a continuous vector space. This phenomenon highlights the growing inclination to utilize graph topologies as a means to improve the precision of predicting DTIs, hence addressing the pressing requirement for effective computational methodologies in the field of drug discovery.ResultsThe present study presents a novel approach called DTIOG for the prediction of DTIs. The methodology employed in this study involves the utilization of a KGE strategy, together with the incorporation of contextual information obtained from protein sequences. More specifically, the study makes use of Protein Bidirectional Encoder Representations from Transformers (ProtBERT) for this purpose. DTIOG utilizes a two-step process to compute embedding vectors using KGE techniques. Additionally, it employs ProtBERT to determine target-target similarity. Different similarity measures, such as Cosine similarity or Euclidean distance, are utilized in the prediction procedure. In addition to the contextual embedding, the proposed unique approach incorporates local representations obtained from the Simplified Molecular Input Line Entry Specification (SMILES) of drugs and the amino acid sequences of protein targets.ConclusionsThe effectiveness of the proposed approach was assessed through extensive experimentation on datasets pertaining to Enzymes, Ion Channels, and G-protein-coupled Receptors. The remarkable efficacy of DTIOG was showcased through the utilization of diverse similarity measures in order to calculate the similarities between drugs and targets. The combination of these factors, along with the incorporation of various classifiers, enabled the model to outperform existing algorithms in its ability to predict DTIs. The consistent observation of this advantage across all datasets underlines the robustness and accuracy of DTIOG in the domain of DTIs. Additionally, our case study suggests that the DTIOG can serve as a valuable tool for discovering new DTIs.

Dataset Information

SumGNN: multi-typed drug interaction prediction via efficient knowledge graph summarization.

Motivation

Results

Availability and implementation

Supplementary information

Publications

SumGNN: multi-typed drug interaction prediction via efficient knowledge graph summarization.

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