A critical comparison of handling zeros in high-dimensional compositional count data

TL;DR

This paper reviews zero-handling strategies in high-dimensional compositional count data from sequencing, highlighting challenges, evaluating imputation methods, and discussing future directions for robust analysis.

Contribution

It systematically compares existing zero-handling methods for compositional count data, emphasizing their limitations and proposing directions for improved approaches.

Findings

Imputation strategies' performance varies with data discreteness and zero inflation.

Violations of continuity assumptions cause numerical instability and bias.

Current methods often fail to jointly address compositional constraints and zero inflation.

Abstract

The growing use of high-throughput sequencing (HTS) has enabled the large-scale production of compositional count data, driving progress in microbiome research. However, such count data are often high-dimensional, over-dispersed, and heavily zero-inflated, and they conflict with the continuity assumptions underlying log-ratio-based compositional data analysis (CoDA), creating substantial methodological challenges. This review provides an overview of zero-handling strategies in compositional data, covering zero-tolerant transformations, imputation approaches for rounded zeros, and statistical models for essential zeros. We specifically highlight the problems that arise when applying the log-ratio framework to sequencing-derived compositional count data, where violations of continuity can induce numerical instabilities and biased statistical inferences. Motivated by these issues, we systematically examine how existing imputation strategies behave when adapted to discrete, zero-inflated count data, including an evaluation of how the discrete, lattice-valued nature of the data affects imputation performance. Overall, this review consolidates scattered methodological developments, clarifies appropriate use cases, and identifies open challenges that motivate future zero-handling frameworks capable of jointly accommodating compositional constraints, zero inflation, and the lattice nature of count data, while also providing a detailed discussion of the comparison results.