Dataset Information

Statistical challenges in longitudinal microbiome data analysis.

ABSTRACT: The microbiome is a complex and dynamic community of microorganisms that co-exist interdependently within an ecosystem, and interact with its host or environment. Longitudinal studies can capture temporal variation within the microbiome to gain mechanistic insights into microbial systems; however, current statistical methods are limited due to the complex and inherent features of the data. We have identified three analytical objectives in longitudinal microbial studies: (1) differential abundance over time and between sample groups, demographic factors or clinical variables of interest; (2) clustering of microorganisms evolving concomitantly across time and (3) network modelling to identify temporal relationships between microorganisms. This review explores the strengths and limitations of current methods to fulfill these objectives, compares different methods in simulation and case studies for objectives (1) and (2), and highlights opportunities for further methodological developments. R tutorials are provided to reproduce the analyses conducted in this review.

SUBMITTER: Kodikara S

PROVIDER: S-EPMC9294433 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Statistical challenges in longitudinal microbiome data analysis.

Kodikara Saritha S Ellul Susan S Lê Cao Kim-Anh KA

Briefings in bioinformatics 20220701 4

The microbiome is a complex and dynamic community of microorganisms that co-exist interdependently within an ecosystem, and interact with its host or environment. Longitudinal studies can capture temporal variation within the microbiome to gain mechanistic insights into microbial systems; however, current statistical methods are limited due to the complex and inherent features of the data. We have identified three analytical objectives in longitudinal microbial studies: (1) differential abundanc ...[more]

PMID: 35830875

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Project description:BackgroundOne of the main challenges of microbiome analysis is its compositional nature that if ignored can lead to spurious results. Addressing the compositional structure of microbiome data is particularly critical in longitudinal studies where abundances measured at different times can correspond to different sub-compositions.ResultsWe developed coda4microbiome, a new R package for analyzing microbiome data within the Compositional Data Analysis (CoDA) framework in both, cross-sectional and longitudinal studies. The aim of coda4microbiome is prediction, more specifically, the method is designed to identify a model (microbial signature) containing the minimum number of features with the maximum predictive power. The algorithm relies on the analysis of log-ratios between pairs of components and variable selection is addressed through penalized regression on the "all-pairs log-ratio model", the model containing all possible pairwise log-ratios. For longitudinal data, the algorithm infers dynamic microbial signatures by performing penalized regression over the summary of the log-ratio trajectories (the area under these trajectories). In both, cross-sectional and longitudinal studies, the inferred microbial signature is expressed as the (weighted) balance between two groups of taxa, those that contribute positively to the microbial signature and those that contribute negatively. The package provides several graphical representations that facilitate the interpretation of the analysis and the identified microbial signatures. We illustrate the new method with data from a Crohn's disease study (cross-sectional data) and on the developing microbiome of infants (longitudinal data).Conclusionscoda4microbiome is a new algorithm for identification of microbial signatures in both, cross-sectional and longitudinal studies. The algorithm is implemented as an R package that is available at CRAN ( https://cran.r-project.org/web/packages/coda4microbiome/ ) and is accompanied with a vignette with a detailed description of the functions. The website of the project contains several tutorials: https://malucalle.github.io/coda4microbiome/.

Project description:We propose a novel framework to learn the spatiotemporal variability in longitudinal 3D shape data sets, which contain observations of objects that evolve and deform over time. This problem is challenging since surfaces come with arbitrary parameterizations and thus, they need to be spatially registered. Also, different deforming objects, hereinafter referred to as 4D surfaces, evolve at different speeds and thus they need to be temporally aligned. We solve this spatiotemporal registration problem using a Riemannian approach. We treat a 3D surface as a point in a shape space equipped with an elastic Riemannian metric that measures the amount of bending and stretching that the surfaces undergo. A 4D surface can then be seen as a trajectory in this space. With this formulation, the statistical analysis of 4D surfaces can be cast as the problem of analyzing trajectories embedded in a nonlinear Riemannian manifold. However, performing the spatiotemporal registration, and subsequently computing statistics, on such nonlinear spaces is not straightforward as they rely on complex nonlinear optimizations. Our core contribution is the mapping of the surfaces to the space of Square-Root Normal Fields (SRNF) where the [Formula: see text] metric is equivalent to the partial elastic metric in the space of surfaces. Thus, by solving the spatial registration in the SRNF space, the problem of analyzing 4D surfaces becomes the problem of analyzing trajectories embedded in the SRNF space, which has a euclidean structure. In this paper, we develop the building blocks that enable such analysis. These include: (1) the spatiotemporal registration of arbitrarily parameterized 4D surfaces even in the presence of large elastic deformations and large variations in their execution rates; (2) the computation of geodesics between 4D surfaces; (3) the computation of statistical summaries, such as means and modes of variation, of collections of 4D surfaces; and (4) the synthesis of random 4D surfaces. We demonstrate the performance of the proposed framework using 4D facial surfaces and 4D human body shapes.

Dataset Information

Statistical challenges in longitudinal microbiome data analysis.

Publications

Statistical challenges in longitudinal microbiome data analysis.

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