The extent to which foundation models can disclose novel chemical, biological, radiation, and nuclear (CBRN) threats to expert users is unclear due to a lack of test cases. I leveraged the unique opportunity presented by an upcoming publication describing a novel catastrophic biothreat - "Technical Report on Mirror Bacteria: Feasibility and Risks" - to conduct a small controlled study before it became public. Graduate-trained biologists tasked with predicting the consequences of releasing mirror E. coli showed no significant differences in rubric-graded accuracy using Claude Sonnet 3.5 new (n=10) or web search only (n=2); both groups scored comparably to a web baseline (28 and 43 versus 36). However, Sonnet reasoned correctly when prompted by a report author, but a smaller model, Haiku 3.5, failed even with author guidance (80 versus 5). These results suggest distinct stages of model capability: Haiku is unable to reason about mirror life even with threat-aware expert guidance (Stage 1), while Sonnet correctly reasons only with threat-aware prompting (Stage 2). Continued advances may allow future models to disclose novel CBRN threats to naive experts (Stage 3) or unskilled users (Stage 4). While mirror life represents only one case study, monitoring new models' ability to reason about privately known threats may allow protective measures to be implemented before widespread disclosure.

Cholera, an acute diarrheal disease, is a serious concern in developing and underdeveloped areas. A qualitative understanding of cholera epidemics aims to foresee transmission patterns based on reported data and mechanistic models. The mechanistic model is a crucial tool for capturing the dynamics of disease transmission and population spread. However, using real-time cholera cases is essential for forecasting the transmission trend. This prospective study seeks to furnish insights into transmission trends through qualitative dynamics followed by machine learning-based forecasting. The Monte Carlo Markov Chain approach is employed to calibrate the proposed mechanistic model. We identify critical parameters that illustrate the disease's dynamics using partial rank correlation coefficient-based sensitivity analysis. The basic reproduction number as a crucial threshold measures asymptotic dynamics. Furthermore, forward bifurcation directs the stability of the infection state, and Hopf bifurcation suggests that trends in transmission may become unpredictable as societal disinfection rates rise. Further, we develop epidemic-informed machine learning models by incorporating mechanistic cholera dynamics into autoregressive integrated moving averages and autoregressive neural networks. We forecast short-term future cholera cases in Malawi by implementing the proposed epidemic-informed machine learning models to support this. We assert that integrating temporal dynamics into the machine learning models can enhance the capabilities of cholera forecasting models. The execution of this mechanism can significantly influence future trends in cholera transmission. This evolving approach can also be beneficial for policymakers to interpret and respond to potential disease systems. Moreover, our methodology is replicable and adaptable, encouraging future research on disease dynamics.

Foodborne gastrointestinal (GI) illness is a common cause of ill health in the UK. However, many cases do not interact with the healthcare system, posing significant challenges for traditional surveillance methods. The growth of publicly available online restaurant reviews and advancements in large language models (LLMs) present potential opportunities to extend disease surveillance by identifying public reports of GI illness. In this study, we introduce a novel annotation schema, developed with experts in GI illness, applied to the Yelp Open Dataset of reviews. Our annotations extend beyond binary disease detection, to include detailed extraction of information on symptoms and foods. We evaluate the performance of open-weight LLMs across these three tasks: GI illness detection, symptom extraction, and food extraction. We compare this performance to RoBERTa-based classification models fine-tuned specifically for these tasks. Our results show that using prompt-based approaches, LLMs achieve micro-F1 scores of over 90% for all three of our tasks. Using prompting alone, we achieve micro-F1 scores that exceed those of smaller fine-tuned models. We further demonstrate the robustness of LLMs in GI illness detection across three bias-focused experiments. Our results suggest that publicly available review text and LLMs offer substantial potential for public health surveillance of GI illness by enabling highly effective extraction of key information. While LLMs appear to exhibit minimal bias in processing, the inherent limitations of restaurant review data highlight the need for cautious interpretation of results.

Motivation: PCR is more economical and quicker than Next Generation Sequencing for detecting target organisms, with primer design being a critical step. In epidemiology with rapidly mutating viruses, designing effective primers is challenging. Traditional methods require substantial manual intervention and struggle to ensure effective primer design across different strains. For organisms with large, similar genomes like Escherichia coli and Shigella flexneri, differentiating between species is also difficult but crucial. Results: We developed Primer C-VAE, a model based on a Variational Auto-Encoder framework with Convolutional Neural Networks to identify variants and generate specific primers. Using SARS-CoV-2, our model classified variants (alpha, beta, gamma, delta, omicron) with 98% accuracy and generated variant-specific primers. These primers appeared with >95% frequency in target variants and <5% in others, showing good performance in in-silico PCR tests. For Alpha, Delta, and Omicron, our primer pairs produced fragments <200 bp, suitable for qPCR detection. The model also generated effective primers for organisms with longer gene sequences like E. coli and S. flexneri. Conclusion: Primer C-VAE is an interpretable deep learning approach for developing specific primer pairs for target organisms. This flexible, semi-automated and reliable tool works regardless of sequence completeness and length, allowing for qPCR applications and can be applied to organisms with large and highly similar genomes.

Antibiotic Resistance (AR) is a critical global health challenge that necessitates the development of cost-effective, efficient, and accurate diagnostic tools. Given the genetic basis of AR, techniques such as Polymerase Chain Reaction (PCR) that target specific resistance genes offer a promising approach for predictive diagnostics using a limited set of key genes. This study introduces GenoARM, a novel framework that integrates reinforcement learning (RL) with transformer-based models to optimize the selection of PCR gene tests and improve AR predictions, leveraging observed metadata for improved accuracy. In our evaluation, we developed several high-performing baselines and compared them using publicly available datasets derived from real-world bacterial samples representing multiple clinically relevant pathogens. The results show that all evaluated methods achieve strong and reliable performance when metadata is not utilized. When metadata is introduced and the number of selected genes increases, GenoARM demonstrates superior performance due to its capacity to approximate rewards for unseen and sparse combinations. Overall, our framework represents a major advancement in optimizing diagnostic tools for AR in clinical settings.

Around 50 percent of Irelands rural population relies on unregulated private wells vulnerable to agricultural runoff and untreated wastewater. High national rates of Shiga toxin-producing Escherichia coli (STEC) and other waterborne illnesses have been linked to well water exposure. Periodic well testing is essential for public health, yet the lack of government incentives places the financial burden on households. Understanding environmental, cognitive, and material factors influencing well-testing behavior is critical. This study employs Agent-Based Modeling (ABM) to simulate policy interventions based on national survey data. The ABM framework, designed for private well-testing behavior, integrates a Deep Q-network reinforcement learning model and Explainable AI (XAI) for decision-making insights. Key features were selected using Recursive Feature Elimination (RFE) with 10-fold cross-validation, while SHAP (Shapley Additive Explanations) provided further interpretability for policy recommendations. Fourteen policy scenarios were tested. The most effective, Free Well Testing plus Communication Campaign, increased participation to 435 out of 561 agents, from a baseline of approximately 5 percent, with rapid behavioral adaptation. Free Well Testing plus Regulation also performed well, with 433 out of 561 agents initiating well testing. Free testing alone raised participation to over 75 percent, with some agents testing multiple times annually. Scenarios with free well testing achieved faster learning efficiency, converging in 1000 episodes, while others took 2000 episodes, indicating slower adaptation. This research demonstrates the value of ABM and XAI in public health policy, providing a framework for evaluating behavioral interventions in environmental health.

Bacterial cells use run-and-tumble motion to climb up attractant concentration gradient in their environment. By extending the uphill runs and shortening the downhill runs the cells migrate towards the higher attractant zones. Motivated by this, we formulate a reinforcement learning (RL) algorithm where an agent moves in one dimension in the presence of an attractant gradient. The agent can perform two actions: either persistent motion in the same direction or reversal of direction. We assign costs for these actions based on the recent history of the agent's trajectory. We ask the question: which RL strategy works best in different types of attractant environment. We quantify efficiency of the RL strategy by the ability of the agent (a) to localize in the favorable zones after large times, and (b) to learn about its complete environment. Depending on the attractant profile and the initial condition, we find an optimum balance is needed between exploration and exploitation to ensure the most efficient performance.

Rapid detection of foodborne bacteria is critical for food safety and quality, yet traditional culture-based methods require extended incubation and specialized sample preparation. This study addresses these challenges by i) enhancing the generalizability of AI-enabled microscopy for bacterial classification using adversarial domain adaptation and ii) comparing the performance of single-target and multi-domain adaptation. Three Gram-positive (Bacillus coagulans, Bacillus subtilis, Listeria innocua) and three Gram-negative (E. coli, Salmonella Enteritidis, Salmonella Typhimurium) strains were classified. EfficientNetV2 served as the backbone architecture, leveraging fine-grained feature extraction for small targets. Few-shot learning enabled scalability, with domain-adversarial neural networks (DANNs) addressing single domains and multi-DANNs (MDANNs) generalizing across all target domains. The model was trained on source domain data collected under controlled conditions (phase contrast microscopy, 60x magnification, 3-h bacterial incubation) and evaluated on target domains with variations in microscopy modality (brightfield, BF), magnification (20x), and extended incubation to compensate for lower resolution (20x-5h). DANNs improved target domain classification accuracy by up to 54.45% (20x), 43.44% (20x-5h), and 31.67% (BF), with minimal source domain degradation (<4.44%). MDANNs achieved superior performance in the BF domain and substantial gains in the 20x domain. Grad-CAM and t-SNE visualizations validated the model's ability to learn domain-invariant features across diverse conditions. This study presents a scalable and adaptable framework for bacterial classification, reducing reliance on extensive sample preparation and enabling application in decentralized and resource-limited environments.

Acetylation of lysine residues (K-Ace) is a post-translation modification occurring in both prokaryotes and eukaryotes. It plays a crucial role in disease pathology and cell biology hence it is important to identify these K-Ace sites. In the past, many machine learning-based models using hand-crafted features and encodings have been used to find and analyze the characteristics of K-Ace sites however these methods ignore long term relationships within sequences and therefore observe performance degradation. In the current work we propose Deep-Ace, a deep learning-based framework using Long-Short-Term-Memory (LSTM) network which has the ability to understand and encode long-term relationships within a sequence. Such relations are vital for learning discriminative and effective sequence representations. In the work reported here, the use of LSTM to extract deep features as well as for prediction of K-Ace sites using fully connected layers for eight different species of prokaryotic models (including B. subtilis, C. glutamicum, E. coli, G. kaustophilus, S. eriocheiris, B. velezensis, S. typhimurium, and M. tuberculosis) has been explored. Our proposed method has outperformed existing state of the art models achieving accuracy as 0.80, 0.79, 0.71, 0.75, 0.80, 0.83, 0.756, and 0.82 respectively for eight bacterial species mentioned above. The method with minor modifications can be used for eukaryotic systems and can serve as a tool for the prognosis and diagnosis of various diseases in humans.

Distinguishing between swarming and swimming, the two principal forms of bacterial movement, holds significant conceptual and clinical relevance. This is because bacteria that exhibit swarming capabilities often possess unique properties crucial to the pathogenesis of infectious diseases and may also have therapeutic potential. Here, we report a deep learning-based swarming classifier that rapidly and autonomously predicts swarming probability using a single blurry image. Compared with traditional video-based, manually-processed approaches, our method is particularly suited for high-throughput environments and provides objective, quantitative assessments of swarming probability. The swarming classifier demonstrated in our work was trained on Enterobacter sp. SM3 and showed good performance when blindly tested on new swarming (positive) and swimming (negative) test images of SM3, achieving a sensitivity of 97.44% and a specificity of 100%. Furthermore, this classifier demonstrated robust external generalization capabilities when applied to unseen bacterial species, such as Serratia marcescens DB10 and Citrobacter koseri H6. It blindly achieved a sensitivity of 97.92% and a specificity of 96.77% for DB10, and a sensitivity of 100% and a specificity of 97.22% for H6. This competitive performance indicates the potential to adapt our approach for diagnostic applications through portable devices or even smartphones. This adaptation would facilitate rapid, objective, on-site screening for bacterial swarming motility, potentially enhancing the early detection and treatment assessment of various diseases, including inflammatory bowel diseases (IBD) and urinary tract infections (UTI).