Archetypal Analysis for Population Genetics

Abstract

The estimation of genetic clusters using genomic data has application from genome-wide association studies (GWAS) to demographic history to polygenic risk scores (PRS) and is expected to play an important role in the analyses of increasingly diverse, large-scale cohorts. However, existing methods are computationally-intensive, prohibitively so in the case of nationwide biobanks. Here we explore Archetypal Analysis as an efficient, unsupervised approach for identifying genetic clusters and for associating individuals with them. Such unsupervised approaches help avoid conflating socially constructed ethnic labels with genetic clusters by eliminating the need for exogenous training labels. We show that Archetypal Analysis yields similar cluster structure to existing unsupervised methods such as ADMIXTURE and provides interpretative advantages. More importantly, we show that since Archetypal Analysis can be used with lower-dimensional representations of genetic data, significant reductions in computational time and memory requirements are possible. When Archetypal Analysis is run in this fashion, it takes several orders of magnitude less compute time than the current standard, ADMIXTURE. Finally, we demonstrate uses ranging across datasets from humans to canids. Author summaryThis work introduces a method that combines the singular value decomposition (SVD) with Archetypal Analysis to perform fast and accurate genetic clustering by first reducing the dimensionality of the space of genomic sequences. Each sequence is described as a convex combination (admixture) of archetypes (cluster representatives) in the reduced dimensional space. We compare this interpretable approach to the widely used genetic clustering algorithm, ADMIXTURE, and show that, without significant degradation in performance, Archetypal Analysis outperforms, offering shorter run times and representational advantages. We include theoretical, qualitative, and quantitative comparisons between both methods.