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Article overview
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Testing for differential abundance in compositional counts data, with application to microbiome studies | | Barak Brill
; Amnon Amir
; Ruth Heller
; | | Date: |
18 Apr 2019 | | Abstract: | In order to identify which taxa differ in the microbiome community across
groups, the relative frequencies of the taxa are measured for each unit in the
group by sequencing PCR amplicons. Statistical inference in this setting is
challenging due to the high number of taxa compared to sampled units, low
prevalence of some taxa, and strong correlations between the different taxa.
Moreover, the total number of sequenced reads per sample is limited by the
sequencing procedure. Thus, the data is compositional: a change of a taxon’s
abundance in the community induces a change in sequenced counts across all
taxa. The data is sparse, with zero counts present either due to biological
variance or limited sequencing depth, i.e. a technical zero. For low abundance
taxa, the chance for technical zeros, is non-negligible and varies between
sample groups. Compositional counts data poses a problem for standard
normalization techniques since technical zeros cannot be normalized in a way
that ensures equality of taxon distributions across sample groups. This problem
is aggravated in settings where the condition studied severely affects the
microbial load of the host. We introduce a novel approach for differential
abundance testing of compositional data, with a non-neglible amount of "zeros".
Our approach uses a set of reference taxa, which are non-differentially
abundant. We suggest a data-adaptive approach for identifying a set of
reference taxa from the data. We demonstrate that existing methods for
differential abundance testing, including methods designed to address
compositionality, do not provide control over the rate of false positive
discoveries when the change in microbial load is vast. We demonstrate that
methods using microbial load measurements do not provide valid inference, since
the microbial load measured cannot adjust for technical zeros. | | Source: | arXiv, 1904.8937 | | Services: | Forum | Review | PDF | Favorites | |
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