arXiv subjects

Lorraine Brennan

Publications and source records attributed to Lorraine Brennan.

6 recordsLinked to original sources

arXiv2025

Missing data imputation using a truncated Gaussian infinite factor model with application to metabolomics data

Metabolomics is the study of small molecules in biological samples. Metabolomics data are typically high-dimensional and contain highly correlated variables and frequent missing values. Both missing at random (MAR) data, due to acquisition or processing errors, and missing not at random (MNAR) data, caused by values falling below detection thresholds, are common. Thus, imputation is a critical component of downstream analysis. Existing imputation methods generally assume one type of data missingness mechanism, or impute values outside the data's physical constraints. A novel truncated Gaussian infinite factor analysis (TGIFA) model is proposed to perform statistically principled and physically realistic imputation in metabolomics data. By incorporating truncated Gaussian assumptions, TGIFA respects the data's physical constraints, while leveraging an infinite latent factor framework to capture high-dimensional dependencies without pre-specifying the number of latent factors. Our Bayesian inference approach enables uncertainty quantification in both the values of the imputed data, and the missing data mechanism. A computationally efficient exchange algorithm enables scalable posterior inference via Markov Chain Monte Carlo. We validate TGIFA through a comprehensive simulation study and demonstrate its utility in a motivating urinary metabolomics dataset, where it yields useful imputations, with associated uncertainty quantification. Open-source R code, available at https://github.com/kfinucane/TGIFA, accompanies TGIFA.

stat.ME↗

arXiv2021

Inferring food intake from multiple biomarkers using a latent variable model

Metabolomic based approaches have gained much attention in recent years due to their promising potential to deliver objective tools for assessment of food intake. In particular, multiple biomarkers have emerged for single foods. However, there is a lack of statistical tools available for combining multiple biomarkers to infer food intake. Furthermore, there is a paucity of approaches for estimating the uncertainty around biomarker based prediction of intake. Here, to facilitate inference on the relationship between multiple metabolomic biomarkers and food intake in an intervention study conducted under the A-DIET research programme, a latent variable model, multiMarker, is proposed. The proposed model draws on factor analytic and mixture of experts models, describing intake as a continuous latent variable whose value gives raise to the observed biomarker values. We employ a mixture of Gaussian distributions to flexibly model the latent variable. A Bayesian hierarchical modelling framework provides flexibility to adapt to different biomarker distributions and facilitates prediction of the latent intake along with its associated uncertainty. Simulation studies are conducted to assess the performance of the proposed multiMarker framework, prior to its application to the motivating application of quantifying apple intake.

stat.ME↗

arXiv2019

Combining biomarker and self-reported dietary intake data: a review of the state of the art and an exposition of concepts

Classical approaches to assessing dietary intake are associated with measurement error. In an effort to address inherent measurement error in dietary self-reported data there is increased interest in the use of dietary biomarkers as objective measures of intake. Furthermore, there is a growing consensus of the need to combine dietary biomarker data with self-reported data. A review of state of the art techniques employed when combining biomarker and self-reported data is conducted. Two predominant methods, the calibration method and the method of triads, emerge as relevant techniques used when combining biomarker and self-reported data to account for measurement errors in dietary intake assessment. Both methods crucially assume measurement error independence. To expose and understand the performance of these methods in a range of realistic settings, their underpinning statistical concepts are unified and delineated, and thorough simulation studies conducted. Results show that violation of the methods' assumptions negatively impacts resulting inference but that this impact is mitigated when the variation of the biomarker around the true intake is small. Thus there is much scope for the further development of biomarkers and models in tandem to achieve the ultimate goal of accurately assessing dietary intake.

stat.AP↗

arXiv2018

Clustering high dimensional mixed data to uncover sub-phenotypes:joint analysis of phenotypic and genotypic data

The LIPGENE-SU.VI.MAX study, like many others, recorded high dimensional continuous phenotypic data and categorical genotypic data. LIPGENE-SU.VI.MAX focuses on the need to account for both phenotypic and genetic factors when studying the metabolic syndrome (MetS), a complex disorder that can lead to higher risk of type 2 diabetes and cardiovascular disease. Interest lies in clustering the LIPGENE-SU.VI.MAX participants into homogeneous groups or sub-phenotypes, by jointly considering their phenotypic and genotypic data, and in determining which variables are discriminatory. A novel latent variable model which elegantly accommodates high dimensional, mixed data is developed to cluster LIPGENE-SU.VI.MAX participants using a Bayesian finite mixture model. A computationally efficient variable selection algorithm is incorporated, estimation is via a Gibbs sampling algorithm and an approximate BIC-MCMC criterion is developed to select the optimal model. Two clusters or sub-phenotypes (`healthy' and `at risk') are uncovered. A small subset of variables is deemed discriminatory which notably includes phenotypic and genotypic variables, highlighting the need to jointly consider both factors. Further, seven years after the LIPGENE-SU.VI.MAX data were collected, participants underwent further analysis to diagnose presence or absence of the MetS. The two uncovered sub-phenotypes strongly correspond to the seven year follow up disease classification, highlighting the role of phenotypic and genotypic factors in the MetS, and emphasising the potential utility of the clustering approach in early screening. Additionally, the ability of the proposed approach to define the uncertainty in sub-phenotype membership at the participant level is synonymous with the concepts of precision medicine and nutrition.

stat.AP↗

arXiv2013

A dynamic probabilistic principal components model for the analysis of longitudinal metabolomic data

In a longitudinal metabolomics study, multiple metabolites are measured from several observations at many time points. Interest lies in reducing the dimensionality of such data and in highlighting influential metabolites which change over time. A dynamic probabilistic principal components analysis (DPPCA) model is proposed to achieve dimension reduction while appropriately modelling the correlation due to repeated measurements. This is achieved by assuming an autoregressive model for some of the model parameters. Linear mixed models are subsequently used to identify influential metabolites which change over time. The proposed model is used to analyse data from a longitudinal metabolomics animal study.

stat.AP↗

arXiv2013

MetSizeR: selecting the optimal sample size for metabolomic studies using an analysis based approach

Background: Determining sample sizes for metabolomic experiments is important but due to the complexity of these experiments, there are currently no standard methods for sample size estimation in metabolomics. Since pilot studies are rarely done in metabolomics, currently existing sample size estimation approaches which rely on pilot data can not be applied. Results: In this article, an analysis based approach called MetSizeR is developed to estimate sample size for metabolomic experiments even when experimental pilot data are not available. The key motivation for MetSizeR is that it considers the type of analysis the researcher intends to use for data analysis when estimating sample size. MetSizeR uses information about the data analysis technique and prior expert knowledge of the metabolomic experiment to simulate pilot data from a statistical model. Permutation based techniques are then applied to the simulated pilot data to estimate the required sample size. Conclusions: The MetSizeR methodology, and a publicly available software package which implements the approach, are illustrated through real metabolomic applications. Sample size estimates, informed by the intended statistical analysis technique, and the associated uncertainty are provided.

stat.AP↗