Motivation The analysis of complex biomedical datasets is becoming central to understanding disease mechanisms, aiding risk stratification and guiding patient management. However, the utility of computational methods is often constrained by their lack of interpretability and accessibility for non-experts, which is particularly relevant in clinically critical areas where rapid initiation of targeted therapies is key.

Results To define diagnostically relevant immune signatures in peritoneal dialysis patients presenting with acute peritonitis, we analysed a comprehensive array of cellular and soluble parameters in cloudy peritoneal effluents. Utilising Tsetlin Machines (TMs), a logic-based machine learning approach, we identified pathogen-specific immune fingerprints for different bacterial groups, each characterised by unique biomarker combinations. Unlike traditional ‘black box’ machine learning models such as artificial neural networks, TMs identified clear, logical rules in the dataset that pointed towards distinctly nuanced immune responses to different types of bacterial infection. This demonstrates unambiguously that even when infecting the same anatomical location and causing clinically indistinguishable symptoms, each type of pathogens interacts in a specific way with the body’s immune system. Importantly, these immune signatures could be easily visualised to facilitate their interpretation, thereby not only enhancing diagnostic accuracy but also potentially allowing for rapid, accurate and transparent decision-making based on the patient’s immune profile. This unique diagnostic capacity of TMs could help deliver clear and actionable insights such as early patient risk stratification and support early and informed treatment choices in advance of conventional microbiological culture results, thus guiding antibiotic stewardship and contributing to improved patient outcomes.

NT and ME are inventors on patents regarding the identification of bacterial infections in peritoneal dialysis patients.

This research was supported by the British Academy's Researchers at Risk Fellowships Programme (RaR/100289), the Wales Kidney Research Unit, NIHR i4i Product Development Award II-LA-0712-20006, MRC Research Grant MR/N023145/1, EPSRC Standard Mode Grant 'KNOT' (EP/Z533841/1) and EPSRC Programme Grant 'SONNETS' (EP/X036006/1).

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The study was approved by the South East Wales Local Ethics Committee (04WSE04/27) and registered on the UK Clinical Research Network Study Portfolio under reference number #11838 "Patient immune responses to infection in peritoneal dialysis" (PERIT-PD). All individuals provided written informed consent.

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