A general kernel machine comparative analysis framework for randomized block designs

MotivationThere are numerous potential confounders, including genetic, environmental, technical, and demographic factors. These factors may be known or unknown, measured or unmeasured; hence, it is extremely challenging to capture them in downstream data analysis. However, randomized block design is an efficient design technique to control confounding factors and to reduce variability within subjects. This helps prevent spurious discoveries and boost test power. I also note that kernel machine comparative analysis is widely employed in high-dimensional omics studies to boost test power by combining possibly weak effects from multiple underlying variants, and also to explore various linear or nonlinear patterns of disparity. ResultsIn this paper, I introduce a general kernel machine comparative analysis framework for randomized block designs, named as KernRBD, to investigate the effects of treatments (e.g., medical treatment, environmental exposure) on the underlying variants. KernRBD is unique in its range of functionalities, including the computation of P-value for global testing and adjusted P-values for pairwise comparisons, as well as visual representation through ordination plotting. KernRBD is practical, requiring only a kernel as input, and also robustly valid based on a resampling scheme not requiring the assumption of normality to be satisfied. I also introduce its omnibus test for a unified and powerful significance testing across multiple input kernels. While its applications should be much broader, I illustrate its use through human microbiome {beta}-diversity analysis in praxis, and its outperformance in significance testing through simulation experiments in silico. Availability and ImplementationKernRBD is available at https://github.com/hk1785/kernrbd.