Controlled Access. Restriction lift date: 2029-12-31
Generative modelling and transformer-based sequence learning for microbiome analysis
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Date
2026-03-31
Authors
Butler, James C.
Journal Title
Journal ISSN
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Publisher
University College Cork
Published Version
Abstract
Two decades of research have established the significant role of the microbiome in human physiology and its association with a wide range of diseases. However, characterizing the relationship between the microbiome and host phenotype remains challenging due to the difficulty of obtaining high-quality samples and the complex statistical properties of microbiome data, including high dimensionality, sparsity, and compositional structure. As sequencing technologies generate increasingly large and high-resolution datasets, there is a growing need for analytical frameworks capable of identifying disease-relevant signals while preserving interpretability. This thesis investigates recent advances in generative modelling and transformer-based architectures for microbiome analysis, with a focus on improving disease classification and assessing their potential to inform our understanding of the human microbiome.
The first chapter provides an overview of generative artificial intelligence and transformer-based methods in the context of microbiome analysis. Chapter 2 introduces MicroDOSE, a hybrid generative framework that combines adversarial and diffusion-based modelling to synthesize biologically realistic microbiome samples, and evaluates the extent to which synthetic data can augment limited training cohorts while preserving key ecological characteristics. Chapter 3 presents LaMe Diffusion, which applies diffusion modelling in latent spaces derived from deep autoencoder representations of microbiome data and shows that classification performance is highly sensitive to representation quality, while positioning diffusion as a strategy for improving the stability of learned latent structure. Chapter 4 develops Meta-STOIC, a transformer-based architecture for disease classification directly from metagenomic sequencing reads, and evaluates the feasibility of predicting disease from sequence-level representations without reliance on predefined taxonomic or functional features. The thesis concludes by outlining future directions for building unified models that can capture the complexity and context-dependent behavior of microbial ecosystems, and help us better understand microbiome–host interactions.
Description
Controlled Access
Keywords
Generative artificial intelligence , Microbiome , Diffusion , Generative adversarial networks , Transformers , Large language models
Citation
Butler, J. C. C. 2026. Generative modelling and transformer-based sequence learning for microbiome analysis. PhD Thesis, University College Cork.