Kieran R. Campbell

Kieran R. Campbell, Christopher Yau

Standard models assign disease progression to discrete categories or stages based on well-characterized clinical markers. However, such a system is potentially at odds with our understanding of the underlying biology, which in highly complex systems may support a (near-)continuous evolution of disease from inception to terminal state. To learn such a continuous disease score one could infer a latent variable from dynamic "omics" data such as RNA-seq that correlates with an outcome of interest such as survival time. However, such analyses may be confounded by additional data such as clinical covariates measured in electronic health records (EHRs). As a solution to this we introduce covariate latent variable models, a novel type of latent variable model that learns a low-dimensional data representation in the presence of two (asymmetric) views of the same data source. We apply our model to TCGA colorectal cancer RNA-seq data and demonstrate how incorporating microsatellite-instability (MSI) status as an external covariate allows us to identify genes that stratify patients on an immune-response trajectory. Finally, we propose an extension termed Covariate Gaussian Process Latent Variable Models for learning nonparametric, nonlinear representations. An R package implementing variational inference for covariate latent variable models is available at http://github.com/kieranrcampbell/clvm.

Kaspar Märtens, Kieran R. Campbell, Christopher Yau

The interpretation of complex high-dimensional data typically requires the use of dimensionality reduction techniques to extract explanatory low-dimensional representations. However, in many real-world problems these representations may not be sufficient to aid interpretation on their own, and it would be desirable to interpret the model in terms of the original features themselves. Our goal is to characterise how feature-level variation depends on latent low-dimensional representations, external covariates, and non-linear interactions between the two. In this paper, we propose to achieve this through a structured kernel decomposition in a hybrid Gaussian Process model which we call the Covariate Gaussian Process Latent Variable Model (c-GPLVM). We demonstrate the utility of our model on simulated examples and applications in disease progression modelling from high-dimensional gene expression data in the presence of additional phenotypes. In each setting we show how the c-GPLVM can extract low-dimensional structures from high-dimensional data sets whilst allowing a breakdown of feature-level variability that is not present in other commonly used dimensionality reduction approaches.