Counts: an outstanding challenge for log-ratio analysis of compositional data in the molecular biosciences.

Thanks to sequencing technology, modern molecular bioscience datasets are often compositions of counts, e.g. counts of amplicons, mRNAs, etc. While there is growing appreciation that compositional data need special analysis and interpretation, less well understood is the discrete nature of these count compositions (or, as we call them, lattice compositions) and the impact this has on statistical analysis, particularly log-ratio analysis (LRA) of pairwise association. While LRA methods are scale-invariant, count compositional data are not; consequently, the conclusions we draw from LRA of lattice compositions depend on the scale of counts involved. We know that additive variation affects the relative abundance of small counts more than large counts; here we show that additive (quantization) variation comes from the discrete nature of count data itself, as well as (biological) variation in the system under study and (technical) variation from measurement and analysis processes. Variation due to quantization is inevitable, but its impact on conclusions depends on the underlying scale and distribution of counts. We illustrate the different distributions of real molecular bioscience data from different experimental settings to show why it is vital to understand the distributional characteristics of count data before applying and drawing conclusions from compositional data analysis methods.