arXiv subjects

Ola Engkvist

Publications and source records attributed to Ola Engkvist.

24 records · Page 2Linked to original sources

arXiv2022

Understanding the Performance of Knowledge Graph Embeddings in Drug Discovery

Knowledge Graphs (KG) and associated Knowledge Graph Embedding (KGE) models have recently begun to be explored in the context of drug discovery and have the potential to assist in key challenges such as target identification. In the drug discovery domain, KGs can be employed as part of a process which can result in lab-based experiments being performed, or impact on other decisions, incurring significant time and financial costs and most importantly, ultimately influencing patient healthcare. For KGE models to have impact in this domain, a better understanding of not only of performance, but also the various factors which determine it, is required. In this study we investigate, over the course of many thousands of experiments, the predictive performance of five KGE models on two public drug discovery-oriented KGs. Our goal is not to focus on the best overall model or configuration, instead we take a deeper look at how performance can be affected by changes in the training setup, choice of hyperparameters, model parameter initialisation seed and different splits of the datasets. Our results highlight that these factors have significant impact on performance and can even affect the ranking of models. Indeed these factors should be reported along with model architectures to ensure complete reproducibility and fair comparisons of future work, and we argue this is critical for the acceptance of use, and impact of KGEs in a biomedical setting.

q-bio.BM↗

arXiv2022

Implications of Topological Imbalance for Representation Learning on Biomedical Knowledge Graphs

Adoption of recently developed methods from machine learning has given rise to creation of drug-discovery knowledge graphs (KG) that utilize the interconnected nature of the domain. Graph-based modelling of the data, combined with KG embedding (KGE) methods, are promising as they provide a more intuitive representation and are suitable for inference tasks such as predicting missing links. One common application is to produce ranked lists of genes for a given disease, where the rank is based on the perceived likelihood of association between the gene and the disease. It is thus critical that these predictions are not only pertinent but also biologically meaningful. However, KGs can be biased either directly due to the underlying data sources that are integrated or due to modeling choices in the construction of the graph, one consequence of which is that certain entities can get topologically overrepresented. We demonstrate the effect of these inherent structural imbalances, resulting in densely-connected entities being highly ranked no matter the context. We provide support for this observation across different datasets, models as well as predictive tasks. Further, we present various graph perturbation experiments which yield more support to the observation that KGE models can be more influenced by the frequency of entities rather than any biological information encoded within the relations. Our results highlight the importance of data modeling choices, and emphasizes the need for practitioners to be mindful of these issues when interpreting model outputs and during KG composition.

cs.LG↗

arXiv2021

A Review of Biomedical Datasets Relating to Drug Discovery: A Knowledge Graph Perspective

Drug discovery and development is a complex and costly process. Machine learning approaches are being investigated to help improve the effectiveness and speed of multiple stages of the drug discovery pipeline. Of these, those that use Knowledge Graphs (KG) have promise in many tasks, including drug repurposing, drug toxicity prediction and target gene-disease prioritisation. In a drug discovery KG, crucial elements including genes, diseases and drugs are represented as entities, whilst relationships between them indicate an interaction. However, to construct high-quality KGs, suitable data is required. In this review, we detail publicly available sources suitable for use in constructing drug discovery focused KGs. We aim to help guide machine learning and KG practitioners who are interested in applying new techniques to the drug discovery field, but who may be unfamiliar with the relevant data sources. The datasets are selected via strict criteria, categorised according to the primary type of information contained within and are considered based upon what information could be extracted to build a KG. We then present a comparative analysis of existing public drug discovery KGs and a evaluation of selected motivating case studies from the literature. Additionally, we raise numerous and unique challenges and issues associated with the domain and its datasets, whilst also highlighting key future research directions. We hope this review will motivate KGs use in solving key and emerging questions in the drug discovery domain.

cs.AI↗

arXiv2021

Parallel Capsule Networks for Classification of White Blood Cells

Capsule Networks (CapsNets) is a machine learning architecture proposed to overcome some of the shortcomings of convolutional neural networks (CNNs). However, CapsNets have mainly outperformed CNNs in datasets where images are small and/or the objects to identify have minimal background noise. In this work, we present a new architecture, parallel CapsNets, which exploits the concept of branching the network to isolate certain capsules, allowing each branch to identify different entities. We applied our concept to the two current types of CapsNet architectures, studying the performance for networks with different layers of capsules. We tested our design in a public, highly unbalanced dataset of acute myeloid leukaemia images (15 classes). Our experiments showed that conventional CapsNets show similar performance than our baseline CNN (ResNeXt-50) but depict instability problems. In contrast, parallel CapsNets can outperform ResNeXt-50, is more stable, and shows better rotational invariance than both, conventional CapsNets and ResNeXt-50.

cs.CV↗

arXiv2017

Application of generative autoencoder in de novo molecular design

A major challenge in computational chemistry is the generation of novel molecular structures with desirable pharmacological and physiochemical properties. In this work, we investigate the potential use of autoencoder, a deep learning methodology, for de novo molecular design. Various generative autoencoders were used to map molecule structures into a continuous latent space and vice versa and their performance as structure generator was assessed. Our results show that the latent space preserves chemical similarity principle and thus can be used for the generation of analogue structures. Furthermore, the latent space created by autoencoders were searched systematically to generate novel compounds with predicted activity against dopamine receptor type 2 and compounds similar to known active compounds not included in the training set were identified.

cs.LG↗

arXiv2017

Molecular De Novo Design through Deep Reinforcement Learning

This work introduces a method to tune a sequence-based generative model for molecular de novo design that through augmented episodic likelihood can learn to generate structures with certain specified desirable properties. We demonstrate how this model can execute a range of tasks such as generating analogues to a query structure and generating compounds predicted to be active against a biological target. As a proof of principle, the model is first trained to generate molecules that do not contain sulphur. As a second example, the model is trained to generate analogues to the drug Celecoxib, a technique that could be used for scaffold hopping or library expansion starting from a single molecule. Finally, when tuning the model towards generating compounds predicted to be active against the dopamine receptor type 2, the model generates structures of which more than 95% are predicted to be active, including experimentally confirmed actives that have not been included in either the generative model nor the activity prediction model.

cs.AI↗