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Analysis of compositions of microbiomes with bias correction.

ABSTRACT: Differential abundance (DA) analysis of microbiome data continues to be a challenging problem due to the complexity of the data. In this article we define the notion of "sampling fraction" and demonstrate a major hurdle in performing DA analysis of microbiome data is the bias introduced by differences in the sampling fractions across samples. We introduce a methodology called Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC), which estimates the unknown sampling fractions and corrects the bias induced by their differences among samples. The absolute abundance data are modeled using a linear regression framework. This formulation makes a fundamental advancement in the field because, unlike the existing methods, it (a) provides statistically valid test with appropriate p-values, (b) provides confidence intervals for differential abundance of each taxon, (c) controls the False Discovery Rate (FDR), (d) maintains adequate power, and (e) is computationally simple to implement.

SUBMITTER: Lin H

PROVIDER: S-EPMC7360769 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Analysis of compositions of microbiomes with bias correction.

Lin Huang H Peddada Shyamal Das SD

Nature communications 20200714 1

Differential abundance (DA) analysis of microbiome data continues to be a challenging problem due to the complexity of the data. In this article we define the notion of "sampling fraction" and demonstrate a major hurdle in performing DA analysis of microbiome data is the bias introduced by differences in the sampling fractions across samples. We introduce a methodology called Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC), which estimates the unknown sampling fractions a ...[more]

PMID: 32665548

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Project description:Meta-analyses conventionally weight study estimates on the inverse of their error variance, in order to maximize precision. Unbiased variability in the estimates of these study-level error variances increases with the inverse of study-level replication. Here, we demonstrate how this variability accumulates asymmetrically across studies in precision-weighted meta-analysis, to cause undervaluation of the meta-level effect size or its error variance (the meta-effect and meta-variance).Small samples, typical of the ecological literature, induce big sampling errors in variance estimation, which substantially bias precision-weighted meta-analysis. Simulations revealed that biases differed little between random- and fixed-effects tests. Meta-estimation of a one-sample mean from 20 studies, with sample sizes of 3-20 observations, undervalued the meta-variance by c. 20%. Meta-analysis of two-sample designs from 20 studies, with sample sizes of 3-10 observations, undervalued the meta-variance by 15%-20% for the log response ratio (lnR); it undervalued the meta-effect by c. 10% for the standardized mean difference (SMD).For all estimators, biases were eliminated or reduced by a simple adjustment to the weighting on study precision. The study-specific component of error variance prone to sampling error and not parametrically attributable to study-specific replication was replaced by its cross-study mean, on the assumptions of random sampling from the same population variance for all studies, and sufficient studies for averaging. Weighting each study by the inverse of this mean-adjusted error variance universally improved accuracy in estimation of both the meta-effect and its significance, regardless of number of studies. For comparison, weighting only on sample size gave the same improvement in accuracy, but could not sensibly estimate significance.For the one-sample mean and two-sample lnR, adjusted weighting also improved estimation of between-study variance by DerSimonian-Laird and REML methods. For random-effects meta-analysis of SMD from little-replicated studies, the most accurate meta-estimates obtained from adjusted weights following conventionally weighted estimation of between-study variance.We recommend adoption of weighting by inverse adjusted-variance for meta-analyses of well- and little-replicated studies, because it improves accuracy and significance of meta-estimates, and it can extend the scope of the meta-analysis to include some studies without variance estimates.

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Analysis of compositions of microbiomes with bias correction.

Publications

Analysis of compositions of microbiomes with bias correction.

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