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Summary Differential abundance tests for compositional data are essential and fundamental in various biomedical applications, such as single-cell, bulk RNA-seq and microbiome data analysis. However, because of the compositional constraint and the prevalence of zero counts in the data, differential abundance analysis on compositional data remains a complicated and unsolved statistical problem. This article proposes a new differential abundance test, the robust differential abundance test, to address these challenges. Compared with existing methods, the robust differential abundance test is simple and computationally efficient, is robust to prevalent zero counts in compositional datasets, can take the data’s compositional nature into account, and has a theoretical guarantee of controlling false discoveries in a general setting. Furthermore, in the presence of observed covariates, the robust differential abundance test can work with covariate-balancing techniques to remove potential confounding effects and draw reliable conclusions. The proposed test is applied to several numerical examples, and its merits are demonstrated using both simulated and real datasets.
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Multiscale adaptive differential abundance analysis in microbial compositional data
Abstract Motivation Differential abundance analysis is an essential and commonly used tool to characterize the difference between microbial communities. However, identifying differentially abundant microbes remains a challenging problem because the observed microbiome data are inherently compositional, excessive sparse, and distorted by experimental bias. Besides these major challenges, the results of differential abundance analysis also depend largely on the choice of analysis unit, adding another practical complexity to this already complicated problem. Results In this work, we introduce a new differential abundance test called the MsRDB test, which embeds the sequences into a metric space and integrates a multiscale adaptive strategy for utilizing spatial structure to identify differentially abundant microbes. Compared with existing methods, the MsRDB test can detect differentially abundant microbes at the finest resolution offered by data and provide adequate detection power while being robust to zero counts, compositional effect, and experimental bias in the microbial compositional dataset. Applications to both simulated and real microbial compositional datasets demonstrate the usefulness of the MsRDB test. Availability and implementation All analyses can be found under https://github.com/lakerwsl/MsRDB-Manuscript-Code.
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- Award ID(s):
- 2113458
- PAR ID:
- 10418647
- Editor(s):
- Alkan, Can
- Date Published:
- Journal Name:
- Bioinformatics
- Volume:
- 39
- Issue:
- 4
- ISSN:
- 1367-4811
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1093/bioinformatics/btad178
