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Biology subjects

Norton, T.

Publications and source records attributed to Norton, T..

4 recordsLinked to original sources

An Expert-Informed Synthetic Animal Data Generator: A Physiology-Consistent Generative Framework for High-Fidelity Animal Digital Twins

Digital twins are increasingly recognized as a transformative technology for precision livestock farming; however, a major bottleneck in their development remains the scarcity of high-quality, high-granularity physiological data. This study introduces the expert-informed conditional diffusion (EICD) framework, a novel approach to synthesizing high-fidelity metabolic time-series trajectories by embedding mechanistic biological principles directly into the generative process. While traditional generative models often prioritize statistical pattern-matching over biological reality, frequently resulting in physiological hallucinations, the EICD framework utilizes a physiology loss function (PhLF) to act as a form of mechanistic regularization. This guardrail penalizes samples that contradict expert-defined constraints, such as the laws of porcine bioenergetics, effectively steering the model toward a realistic physiological manifold. The framework was validated using an empirical dataset of growing pigs under varying thermal conditions. Quantitative results demonstrate near-perfect statistical distributional fidelity, with the model achieving an average Jensen-Shannon divergence (JSD) of 0.062 and a Kullback-Leibler divergence (KLD) of 0.19. The full EICD model produced a mean energy expenditure (EE) of 284.94 {+/-} 38.70 kJ/kg/day, mirroring the empirical average of 281.33 {+/-} 41.58 kJ/kg/day. In contrast, the standard generative diffusion model (i.e., with no physiology guardrail) exhibited significant distributional drift, yielding a mean EE of 334.41 kJ/kg/day. The biological integrity of the model was further assessed using the biological violation rate (BVR), a novel metric defined as the percentage of generated samples that fall outside the physically possible metabolic boundaries established by species-specific laws. While the standard diffusion model produced frequent biological artifacts, the EICD framework successfully suppressed these hallucinations, ensuring that synthetic trajectories remain strictly grounded in mechanistic laws. Despite these advancements, limitations remain at physiological extremes where individual stochasticity is high. By providing a reliable method for generating physiology-consistent synthetic data, this framework provides a robust foundation for the next generation of animal digital twins. HighlightsO_LIA novel expert-informed conditional diffusion (EICD) framework is proposed for physiology-consistent synthetic data generation in precision livestock farming. C_LIO_LIA physiology loss function (PhLF) embeds species-specific bioenergetic laws directly into the generative process as a mechanistic guardrail. C_LIO_LIThe framework achieves near-perfect distributional fidelity (JSD = 0.062) while suppressing physiological hallucinations (BVR = 0.93%). C_LIO_LIAn ablation study confirms that biological consistency is not an emergent property of standard diffusion models but requires explicit mechanistic constraints. C_LIO_LIThe framework provides a scalable solution for synthetic data augmentation in precision livestock farming, supporting the 3Rs and enabling high-throughput in silico experimentation. C_LI

bioengineering↗

Towards an AI-based knowledge assistant for goat farmers based on Retrieval-Augmented Generation

Large language models (LLMs) are increasingly being recognised as valuable knowledge communication tools in many industries. However, their application in livestock farming remains limited, being constrained by several factors not least the availability, diversity and complexity of knowledge sources. This study introduces an intelligent knowledge assistant system designed to support health management in farmed goats. Leveraging the Retrieval-Augmented Generation (RAG), two structured knowledge processing methods - table textualization and decision-tree textualization - were proposed to enhance large language models (LLMs) understanding of heterogeneous data formats. Based on these methods, a domain-specific goat farming knowledge base was established to improve LLMs capacity for cross-scenario generalization. The knowledge base spans five key domains: Disease Prevention and Treatment, Nutrition Management, Rearing Management, Goat Milk Management, and Basic Farming Knowledge. Additionally, an online search module is integrated to enable real-time retrieval of up-to-date information. To evaluate system performance, six ablation experiments were conducted to examine the contribution of each component. The results demonstrated that heterogeneous knowledge fusion method achieved the best results, with mean accuracies of 87.90% on the validation set and 84.22% on the test set. Across the text-based, table-based, decision-tree based Q&A tasks, accuracy consistently exceeded 85%, validating the effectiveness of structured knowledge fusion within a modular design. Error analysis identified omission as the predominant error category, highlighting opportunities to further improve retrieval coverage and context integration. In conclusion, the results highlight the robustness and reliability of the proposed system for practical applications in goat farming.

bioengineering↗

The cell type composition of the adult mouse brain revealed by single cell and spatial genomics

The function of the mammalian brain relies upon the specification and spatial positioning of diversely specialized cell types. Yet, the molecular identities of the cell types, and their positions within individual anatomical structures, remain incompletely known. To construct a comprehensive atlas of cell types in each brain structure, we paired high-throughput single-nucleus RNA-seq with Slide-seq-a recently developed spatial transcriptomics method with near-cellular resolution-across the entire mouse brain. Integration of these datasets revealed the cell type composition of each neuroanatomical structure. Cell type diversity was found to be remarkably high in the midbrain, hindbrain, and hypothalamus, with most clusters requiring a combination of at least three discrete gene expression markers to uniquely define them. Using these data, we developed a framework for genetically accessing each cell type, comprehensively characterized neuropeptide and neurotransmitter signaling, elucidated region-specific specializations in activity-regulated gene expression, and ascertained the heritability enrichment of neurological and psychiatric phenotypes. These data, available as an online resource (BrainCellData.org) should find diverse applications across neuroscience, including the construction of new genetic tools, and the prioritization of specific cell types and circuits in the study of brain diseases.

neuroscience↗

In vitro and in vivo preclinical studies predict REGEN-COV protection against emergence of viral escape in humans

Monoclonal antibodies against SARS-CoV-2 are a clinically validated therapeutic option against COVID-19. As rapidly emerging virus mutants are becoming the next major concern in the fight against the global pandemic, it is imperative that these therapeutic treatments provide coverage against circulating variants and do not contribute to development of treatment emergent resistance. To this end, we investigated the sequence diversity of the spike protein and monitored emergence of minor virus variants in SARS-COV-2 isolates found in COVID-19 patients or identified from preclinical in vitro and in vivo studies. This study demonstrates that a combination of non-competing antibodies, REGEN-COV, not only provides full coverage against current variants of concern/interest but also protects against emergence of new such variants and their potential seeding into the population in a clinical setting.

microbiology↗