Nicholas Geard

Roben Delos Reyes, Daniel Capurro, Nicholas Geard

ML models in healthcare are typically evaluated using curated real-world EHR data. A key limitation of such evaluations is that they may fail to assess the robustness of ML models to changes in the data at deployment, which is a common issue because EHR data used for ML model development cannot capture all such changes. Mass casualty incidents (MCIs) caused by disasters are critical instances where this will be an issue, as they induce rare, uncertain, and novel changes to routine system conditions. Because real-world EHR data from MCIs are often limited or unavailable, assessing ML robustness under such conditions before deployment remains challenging. Here, we propose an agent-based modelling approach for generating synthetic EHR data to evaluate the robustness of ML models under MCI scenarios. We use real-world EHR data to develop and calibrate an agent-based model (ABM) of an emergency department (ED) that explicitly models patient arrivals, resource capacity, and clinical workflow. By changing these system conditions to reflect plausible MCI scenarios, the ED model generates synthetic versions of the real-world EHR data that exhibit shifts in system behaviour. Using these synthetic data, we test ML models for predicting length of stay. We observed consistent declines in recall under MCI conditions relative to baseline system conditions, resulting in an increase in the number of patients with prolonged length of stay that were missed by the ML models. These results highlight the impact of changes in system conditions on patient outcomes, EHR data, and ML model performance. Our work establishes ABM-based synthetic EHR data generation as a proactive and systematic approach for evaluating the robustness of ML models under MCI or other system conditions not captured in real-world EHR data, supporting the safer and more effective deployment of ML models in healthcare systems.

Bruna Moreira da Silva, David B. Ascher, Nicholas Geard et al.

Antibodies, a prominent class of approved biologics, play a crucial role in detecting foreign antigens. The effectiveness of antigen neutralisation and elimination hinges upon the strength, sensitivity, and specificity of the paratope-epitope interaction, which demands resource-intensive experimental techniques for characterisation. In recent years, artificial intelligence and machine learning methods have made significant strides, revolutionising the prediction of protein structures and their complexes. The past decade has also witnessed the evolution of computational approaches aiming to support immunotherapy design. This review focuses on the progress of machine learning-based tools and their frameworks in the domain of B-cell immunotherapy design, encompassing linear and conformational epitope prediction, paratope prediction, and antibody design. We mapped the most commonly used data sources, evaluation metrics, and method availability and thoroughly assessed their significance and limitations, discussing the main challenges ahead.

Gourab Ghosh Roy, Nicholas Geard, Karin Verspoor et al.

Survival risk prediction using gene expression data is important in making treatment decisions in cancer. Standard neural network (NN) survival analysis models are black boxes with lack of interpretability. More interpretable visible neural network (VNN) architectures are designed using biological pathway knowledge. But they do not model how pathway structures can change for particular cancer types. We propose a novel Mutated Pathway VNN or MPVNN architecture, designed using prior signaling pathway knowledge and gene mutation data-based edge randomization simulating signal flow disruption. As a case study, we use the PI3K-Akt pathway and demonstrate overall improved cancer-specific survival risk prediction results of MPVNN over standard non-NN and other similar sized NN survival analysis methods. We show that trained MPVNN architecture interpretation, which points to smaller sets of genes connected by signal flow within the PI3K-Akt pathway that are important in risk prediction for particular cancer types, is reliable.