Combining drugs, a phenomenon often referred to as polypharmacy, can induce additional adverse effects. The identification of adverse combinations is a key task in pharmacovigilance. In this context, in silico approaches based on machine learning are promising as they can learn from a limited number of combinations to predict for all. In this work, we identify various subtasks in predicting effects caused by drug–drug interaction. Predicting drug–drug interaction effects for drugs that already exist is very different from predicting outcomes for newly developed drugs, commonly called a cold-start problem. We propose suitable validation schemes for the different subtasks that emerge. These validation schemes are critical to correctly assess the performance. We develop a new model that obtains AUC-ROC $=0.843$ for the hardest cold-start task up to AUC-ROC $=0.957$ for the easiest one on the benchmark dataset of Zitnik et al. Finally, we illustrate how our predictions can be used to improve post-market surveillance systems or detect drug–drug interaction effects earlier during drug development.

Background: Disability progression is a key milestone in the disease evolution of people with multiple sclerosis (PwMS). Prediction models of the probability of disability progression have not yet reached the level of trust needed to be adopted in the clinic. A common benchmark to assess model development in multiple sclerosis is also currently lacking. Methods: Data of adult PwMS with a follow-up of at least three years from 146 MS centers, spread over 40 countries and collected by the MSBase consortium was used. With basic inclusion criteria for quality requirements, it represents a total of 15, 240 PwMS. External validation was performed and repeated five times to assess the significance of the results. Transparent Reporting for Individual Prognosis Or Diagnosis (TRIPOD) guidelines were followed. Confirmed disability progression after two years was predicted, with a confirmation window of six months. Only routinely collected variables were used such as the expanded disability status scale, treatment, relapse information, and MS course. To learn the probability of disability progression, state-of-the-art machine learning models were investigated. The discrimination performance of the models is evaluated with the area under the receiver operator curve (ROC-AUC) and under the precision recall curve (AUC-PR), and their calibration via the Brier score and the expected calibration error. All our preprocessing and model code are available at https://gitlab.com/edebrouwer/ms_benchmark, making this task an ideal benchmark for predicting disability progression in MS. Findings: Machine learning models achieved a ROC-AUC of 0⋅71 ± 0⋅01, an AUC-PR of 0⋅26 ± 0⋅02, a Brier score of 0⋅1 ± 0⋅01 and an expected calibration error of 0⋅07 ± 0⋅04. The history of disability progression was identified as being more predictive for future disability progression than the treatment or relapses history. Conclusions: Good discrimination and calibration performance on an external validation set is achieved, using only routinely collected variables. This suggests machine-learning models can reliably inform clinicians about the future occurrence of progression and are mature for a clinical impact study.

Advances in bioinformatics are primarily due to new algorithms for processing diverse biological data sources. While sophisticated alignment algorithms have been pivotal in analyzing biological sequences, deep learning has substantially transformed bioinformatics, addressing sequence, structure, and functional analyses. However, these methods are incredibly data-hungry, compute-intensive, and hard to interpret. Hyperdimensional computing (HDC) has recently emerged as an exciting alternative. The key idea is that random vectors of high dimensionality can represent concepts such as sequence identity or phylogeny. These vectors can then be combined using simple operators for learning, reasoning, or querying by exploiting the peculiar properties of high-dimensional spaces. Our work reviews and explores HDC’s potential for bioinformatics, emphasizing its efficiency, interpretability, and adeptness in handling multimodal and structured data. HDC holds great potential for various omics data searching, biosignal analysis, and health applications.

Integral transforms are invaluable mathematical tools to map functions into spaces where they are easier to characterize. We introduce the hyperdimensional transform as a new kind of integral transform. It converts square-integrable functions into noise-robust, holographic, high-dimensional representations called hyperdimensional vectors. The central idea is to approximate a function by a linear combination of random functions. We formally introduce a set of stochastic, orthogonal basis functions and define the hyperdimensional transform and its inverse. We discuss general transform-related properties such as its uniqueness, approximation properties of the inverse transform, and the representation of integrals and derivatives. The hyperdimensional transform offers a powerful, flexible framework that connects closely with other integral transforms, such as the Fourier, Laplace, and fuzzy transforms. Moreover, it provides theoretical foundations and new insights for the field of hyperdimensional computing, a computing paradigm that is rapidly gaining attention for efficient and explainable machine learning algorithms, with potential applications in statistical modelling and machine learning. In addition, we provide straightforward and easily understandable code, which can function as a tutorial and allows for the reproduction of the demonstrated examples, from computing the transform to solving differential equations.

Integral transforms are invaluable mathematical tools to map functions into spaces where they are easier to characterize. We introduce the hyperdimensional transform as a new kind of integral transform. It converts square-integrable functions into noise-robust, holographic, high-dimensional representations called hyperdimensional vectors. The central idea is to approximate a function by a linear combination of random functions. We formally introduce a set of stochastic, orthogonal basis functions and define the hyperdimensional transform and its inverse. We discuss general transform-related properties such as its uniqueness, approximation properties of the inverse transform, and the representation of integrals and derivatives. The hyperdimensional transform offers a powerful, flexible framework that connects closely with other integral transforms, such as the Fourier, Laplace, and fuzzy transforms. Moreover, it provides theoretical foundations and new insights for the field of hyperdimensional computing, a computing paradigm that is rapidly gaining attention for efficient and explainable machine learning algorithms, with potential applications in statistical modelling and machine learning. In addition, we provide straightforward and easily understandable code, which can function as a tutorial and allows for the reproduction of the demonstrated examples, from computing the transform to solving differential equations.

A stagewise graph has distinct edge types that represent the different stages. Two nodes can be connected by an edge of the current stage only if an edge of the preceding one is already connecting them. Stagewise graphs can represent many kinds of interactions. For example, a jobseeker-vacancy interaction can be labeled by the subsequent edge types click , apply , job interview , and, finally, hired . Also, biological and medical interactions, such as infection processes or administration of drugs, often occur in stages. In this work, we formalize link prediction problems on such graphs as ‘stagewise link prediction’. Though relevant and rapidly gaining attention, these types of problems are to date highly underexplored. We identify and address arising difficulties, such as competition in stagewise networks. We explore an activation function for stagewise modelling and an evaluation strategy that satisfies the stagewise constraints. We confirm our insights through a set of experiments on both well-chosen simulated data sets and real data related to job recommendation and synthetic biology.