scholarly journals Tree-aggregated predictive modeling of microbiome data

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jacob Bien ◽  
Xiaohan Yan ◽  
Léo Simpson ◽  
Christian L. Müller

AbstractModern high-throughput sequencing technologies provide low-cost microbiome survey data across all habitats of life at unprecedented scale. At the most granular level, the primary data consist of sparse counts of amplicon sequence variants or operational taxonomic units that are associated with taxonomic and phylogenetic group information. In this contribution, we leverage the hierarchical structure of amplicon data and propose a data-driven and scalable tree-guided aggregation framework to associate microbial subcompositions with response variables of interest. The excess number of zero or low count measurements at the read level forces traditional microbiome data analysis workflows to remove rare sequencing variants or group them by a fixed taxonomic rank, such as genus or phylum, or by phylogenetic similarity. By contrast, our framework, which we call  (ee-ggregation of ompositional data), learns data-adaptive taxon aggregation levels for predictive modeling, greatly reducing the need for user-defined aggregation in preprocessing while simultaneously integrating seamlessly into the compositional data analysis framework. We illustrate the versatility of our framework in the context of large-scale regression problems in human gut, soil, and marine microbial ecosystems. We posit that the inferred aggregation levels provide highly interpretable taxon groupings that can help microbiome researchers gain insights into the structure and functioning of the underlying ecosystem of interest.

2020 ◽  
Author(s):  
Jacob Bien ◽  
Xiaohan Yan ◽  
Léo Simpson ◽  
Christian L. Müller

AbstractModern high-throughput sequencing technologies provide low-cost microbiome survey data across all habitats of life at unprecedented scale. At the most granular level, the primary data consist of sparse counts of amplicon sequence variants or operational taxonomic units that are associated with taxonomic and phylogenetic group information. In this contribution, we leverage the hierarchical structure of amplicon data and propose a data-driven, parameter-free, and scalable tree-guided aggregation framework to associate microbial subcompositions with response variables of interest. The excess number of zero or low count measurements at the read level forces traditional microbiome data analysis workflows to remove rare sequencing variants or group them by a fixed taxonomic rank, such as genus or phylum, or by phylogenetic similarity. By contrast, our framework, which we call trac (tree-aggregation of compositional data), learns data-adaptive taxon aggregation levels for predictive modeling making user-defined aggregation obsolete while simultaneously integrating seamlessly into the compositional data analysis framework. We illustrate the versatility of our framework in the context of large-scale regression problems in human-gut, soil, and marine microbial ecosystems. We posit that the inferred aggregation levels provide highly interpretable taxon groupings that can help microbial ecologists gain insights into the structure and functioning of the underlying ecosystem of interest.


2016 ◽  
Vol 62 (8) ◽  
pp. 692-703 ◽  
Author(s):  
Gregory B. Gloor ◽  
Gregor Reid

A workshop held at the 2015 annual meeting of the Canadian Society of Microbiologists highlighted compositional data analysis methods and the importance of exploratory data analysis for the analysis of microbiome data sets generated by high-throughput DNA sequencing. A summary of the content of that workshop, a review of new methods of analysis, and information on the importance of careful analyses are presented herein. The workshop focussed on explaining the rationale behind the use of compositional data analysis, and a demonstration of these methods for the examination of 2 microbiome data sets. A clear understanding of bioinformatics methodologies and the type of data being analyzed is essential, given the growing number of studies uncovering the critical role of the microbiome in health and disease and the need to understand alterations to its composition and function following intervention with fecal transplant, probiotics, diet, and pharmaceutical agents.


mSphere ◽  
2017 ◽  
Vol 2 (5) ◽  
Author(s):  
Gaorui Bian ◽  
Gregory B. Gloor ◽  
Aihua Gong ◽  
Changsheng Jia ◽  
Wei Zhang ◽  
...  

ABSTRACT We report the large-scale use of compositional data analysis to establish a baseline microbiota composition in an extremely healthy cohort of the Chinese population. This baseline will serve for comparison for future cohorts with chronic or acute disease. In addition to the expected difference in the microbiota of children and adults, we found that the microbiota of the elderly in this population was similar in almost all respects to that of healthy people in the same population who are scores of years younger. We speculate that this similarity is a consequence of an active healthy lifestyle and diet, although cause and effect cannot be ascribed in this (or any other) cross-sectional design. One surprising result was that the gut microbiota of persons in their 20s was distinct from those of other age cohorts, and this result was replicated, suggesting that it is a reproducible finding and distinct from those of other populations. The microbiota of the aged is variously described as being more or less diverse than that of younger cohorts, but the comparison groups used and the definitions of the aged population differ between experiments. The differences are often described by null hypothesis statistical tests, which are notoriously irreproducible when dealing with large multivariate samples. We collected and examined the gut microbiota of a cross-sectional cohort of more than 1,000 very healthy Chinese individuals who spanned ages from 3 to over 100 years. The analysis of 16S rRNA gene sequencing results used a compositional data analysis paradigm coupled with measures of effect size, where ordination, differential abundance, and correlation can be explored and analyzed in a unified and reproducible framework. Our analysis showed several surprising results compared to other cohorts. First, the overall microbiota composition of the healthy aged group was similar to that of people decades younger. Second, the major differences between groups in the gut microbiota profiles were found before age 20. Third, the gut microbiota differed little between individuals from the ages of 30 to >100. Fourth, the gut microbiota of males appeared to be more variable than that of females. Taken together, the present findings suggest that the microbiota of the healthy aged in this cross-sectional study differ little from that of the healthy young in the same population, although the minor variations that do exist depend upon the comparison cohort. IMPORTANCE We report the large-scale use of compositional data analysis to establish a baseline microbiota composition in an extremely healthy cohort of the Chinese population. This baseline will serve for comparison for future cohorts with chronic or acute disease. In addition to the expected difference in the microbiota of children and adults, we found that the microbiota of the elderly in this population was similar in almost all respects to that of healthy people in the same population who are scores of years younger. We speculate that this similarity is a consequence of an active healthy lifestyle and diet, although cause and effect cannot be ascribed in this (or any other) cross-sectional design. One surprising result was that the gut microbiota of persons in their 20s was distinct from those of other age cohorts, and this result was replicated, suggesting that it is a reproducible finding and distinct from those of other populations.


2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Antoni Susin ◽  
Yiwen Wang ◽  
Kim-Anh Lê Cao ◽  
M Luz Calle

Abstract Though variable selection is one of the most relevant tasks in microbiome analysis, e.g. for the identification of microbial signatures, many studies still rely on methods that ignore the compositional nature of microbiome data. The applicability of compositional data analysis methods has been hampered by the availability of software and the difficulty in interpreting their results. This work is focused on three methods for variable selection that acknowledge the compositional structure of microbiome data: selbal, a forward selection approach for the identification of compositional balances, and clr-lasso and coda-lasso, two penalized regression models for compositional data analysis. This study highlights the link between these methods and brings out some limitations of the centered log-ratio transformation for variable selection. In particular, the fact that it is not subcompositionally consistent makes the microbial signatures obtained from clr-lasso not readily transferable. Coda-lasso is computationally efficient and suitable when the focus is the identification of the most associated microbial taxa. Selbal stands out when the goal is to obtain a parsimonious model with optimal prediction performance, but it is computationally greedy. We provide a reproducible vignette for the application of these methods that will enable researchers to fully leverage their potential in microbiome studies.


2016 ◽  
Vol 45 (4) ◽  
pp. 73-87 ◽  
Author(s):  
Gregory Brian Gloor ◽  
Jean M. Macklaim ◽  
Michael Vu ◽  
Andrew D. Fernandes

High throughput sequencing generates sparse compositional data, yet these datasets are rarely analyzed using a compositional approach. In addition, the variation inherent in these datasets is rarely acknowledged, but ignoring it can result in many false positive inferences. We demonstrate that examination of point estimates of the data can result in false positive results, even with appropriate zero replacement approaches, using an in vitro selection dataset with an outside standard of truth. The variation inherent in real high-throughput sequencing datasets is demonstrated, and we show that this varia- tion can be approximated, and hence accounted for, by Monte-Carlo sampling from the Dirichlet distribution. This approximation when used by itself is itself problematic, but becomes useful when coupled with a log-ratio approach commonly used in compositional data analysis. Thus, the approach illustrated here that merges Bayesian estimation with principles of compositional data analysis should be generally useful for high-dimensional count compositional data of the type generated by high throughput sequencing. 


2018 ◽  
Vol 47 (1) ◽  
pp. 3-31 ◽  
Author(s):  
Juan José Egozcue ◽  
Vera Pawlowsky-Glahn ◽  
Gregory B. Gloor

With compositional data ordinary covariation indexes, designed for real random variables, fail to describe dependence. There is a need for compositional alternatives to covariance and correlation. Based on the Euclidean structure of the simplex, called Aitchison geometry, compositional association is identied to a linear restriction of the sample space when a log-contrast is constant. In order to simplify interpretation, a sparse and simple version of compositional association is dened in terms of balances which are constant across the sample. It is called b-association. This kind of association of compositional variables is extended to association between groups of compositional variables. In practice, exact b-association seldom occurs, and measures of degree of b-association are reviewed based on those previously proposed. Also, some techniques for testing b-association are studied. These techniques are applied to available oral microbiome data to illustrate both their advantages and diculties. Both testing and measurements of b-association appear to be quite sensible to heterogeneities in the studied populations and to outliers.


2021 ◽  
Vol 14 (12) ◽  
pp. 7657-7680
Author(s):  
Yangjunjie Xu-Yang ◽  
Rémi Losno ◽  
Fabrice Monna ◽  
Jean-Louis Rajot ◽  
Mohamed Labiadh ◽  
...  

Abstract. This paper presents a new sampling head design and the method used to evaluate it. The elemental composition of aerosols collected by two different sampling devices in a semi-arid region of Tunisia is compared by means of compositional perturbation vectors and biplots. This set of underused mathematical tools belongs to a family of statistics created specifically to deal with compositional data. The two sampling devices operate at a flow rate in the range of 1 m3 h−1, with a cut-off diameter of 10 µm. The first device is a low-cost laboratory-made system, where the largest particles are removed by gravitational settling in a vertical tube. This new system will be compared to the second device, a brand-new standard commercial PM10 sampling head, where size segregation is achieved by particle impaction on a metal surface. A total of 44 elements (including rare earth elements, REEs, together with Al, As, Ba, Be, Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Mo, Na, Ni, P, Pb, Rb, S, Sc, Se, Sr, Ti, Tl, U, V, Zn, and Zr) were analysed in 16 paired samples, collected during a 2-week field campaign in Tunisian dry lands, close to source areas, with high levels of large particles. The contrasting meteorological conditions encountered during the field campaign allowed a broad range of aerosol compositions to be collected, with very different aerosol mass concentrations. The compositional data analysis (CoDA) tools show that no compositional differences were observed between samples collected simultaneously by the two devices. The mass concentration of the particles collected was estimated through chemical analysis. Results for the two sampling devices were very similar to those obtained from an online aerosol weighing system, TEOM (tapered element oscillating microbalance), installed next to them. These results suggest that the commercial PM10 impactor head can therefore be replaced by the decanter, without any measurable bias, for the determination of chemical composition and for further assessment of PM10 concentrations in source regions.


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