Paul Clarke

• Paul, Clarke; Cmelo, Ivan; Helin, Runar; Shende, Mayur Kishor; Granmo, Ole-Christoffer & Fayne, Darren (2026). The Tsetlin Machine: A “Third Way” in QSAR Modeling. Journal of Chemical Information and Modeling. ISSN 1549-9596. 66(11), s. 6250–6270. doi: 10.1021/acs.jcim.5c03109. Fulltekst i vitenarkiv Vis sammendrag

  Advances in Quantitative Structure Activity Relationship (QSAR) are led by two core paradigms, (1) descriptor engineering, where complex fixed-length vectors of compounds are generated and conventional ML methods are applied to those representations and (2) graphical chemical inputs (e.g., Simplified Molecular Input Line Entry System (SMILES), 2D-graph) being provided to deep learning neural network (NN) models, which construct their own internal representations of molecules and learn iteratively over them. Here we present the Tsetlin Machine (TM)─which combines the accuracy and easy-use of existing rule-based QSAR ML methods (e.g., RF and XGBoost), the iterative learning aspect of NN algorithms and its intrinsic interpretability. The TM uses teams of finite-state automata which capture frequent patterns as propositional logic (clauses) via reinforcement learning. The benchmarking pipeline presented here demonstrates that TM-QSAR coupled with ECFP4 descriptors frequently performs better than existing rule-based QSAR methods for ROC-AUC, PRC-AUC and PPV, with a high capacity for interscaffold generalization. However, due to the binary nature of TM-QSAR, performance it is currently limited when descretised continuous descriptors are used. TM-QSAR demonstrated particularly impressive classification scores for MOR (ROC-AUC = 0.87, PRC-AUC = 0.77) and CYPA4 (ROC-AUC = 0.92, PRC-AUC = 0.63), when compared to RF and XGBoost. Using TM in combination with substructural fingerprinting descriptors allows for an interpretability suite which can be extracted directly from clauses. Here we detail molecule property maps (TM-MPM) to view atom-wise TM-QSAR bioactivity contributions for single molecules and closed-form WAC scores (Weights × Activations × Clauses) for descriptor-wise contributions to regions of predicted chemical space. These methods show strong alignment of TM-QSAR interpretations to known ligand–protein interactions of the MOR target and gives nonlinear, conditional interpretations for greater predicted bioactivity. Given this combination of accuracy, computational efficiency and interpretability, we provide a basis for TM-QSAR to be explored as a standard methodology in virtual screening toolkits.

• Abughalia, Abedalrahman; Flynn, Mairead; Paul, Clarke; Fayne, Darren & Gobbo, Oliviero L. (2025). The Use of Computational Approaches to Design Nanodelivery Systems. Nanomaterials. 15(17). doi: 10.3390/nano15171354. Fulltekst i vitenarkiv Vis sammendrag

  Nano-based drug delivery systems present a promising approach to improve the efficacy and safety of therapeutics by enabling targeted drug transport and controlled release. In parallel, computational approaches—particularly Molecular Dynamics (MD) simulations and Artificial Intelligence (AI)—have emerged as transformative tools to accelerate nanocarrier design and optimise their properties. MD simulations provide atomic-to-mesoscale insights into nanoparticle interactions with biological membranes, elucidating how factors such as surface charge density, ligand functionalisation and nanoparticle size affect cellular uptake and stability. Complementing MD simulations, AI-driven models accelerate the discovery of lipid-based nanoparticle formulations by analysing vast chemical datasets and predicting optimal structures for gene delivery and vaccine development. By harnessing these computational approaches, researchers can rapidly refine nanoparticle composition to improve biocompatibility, reduce toxicity and achieve more precise drug targeting. This review synthesises key advances in MD simulations and AI for two leading nanoparticle platforms (gold and lipid nanoparticles) and highlights their role in enhancing therapeutic performance. We evaluate how in silico models guide experimental validation, inform rational design strategies and ultimately streamline the transition from bench to bedside. Finally, we address key challenges such as data scarcity and complex in vivo dynamics and propose future directions for integrating computational insights into next generation nanodelivery systems.

• Halenka, Vojtech; Kadhim, Ahmed Khalid; Paul, Clarke; Bhattarai, Bimal; Saha, Rupsa & Granmo, Ole-Christoffer [Vis alle 8 forfattere av denne artikkelen] (2024). Exploring Effects of Hyperdimensional Vectors for Tsetlin Machines. I NN, NN (Red.), 2024 International Symposium on the Tsetlin Machine (ISTM). IEEE (Institute of Electrical and Electronics Engineers). ISSN 9798331504984. doi: 10.1109/ISTM62799.2024.10931546. Fulltekst i vitenarkiv Vis sammendrag

  Tsetlin machines (TMs) have been successful in several application domains, operating with high efficiency on Boolean representations of the input data. However, Booleanizing complex data structures such as sequences, graphs, images, signal spectra, chemical compounds, and natural language is non-trivial. In this paper, we propose a hypervector (HV) based method for expressing arbitrarily large sets of concepts associated with any input data. Using a hyperdimensional space to build vectors drastically expands the capacity and flexibility of the TM. We demonstrate how images, chemical compounds, and natural language text are encoded according to the proposed method, and how the resulting HV -powered TM can achieve significantly higher accuracy and faster learning on well-known benchmarks. Our results thus open up a new research direction for TMs, namely how to expand and exploit the benefits of operating in hyperspace, including new booleanization strategies, optimization of TM inference and learning, as well as new TM applications.

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