Archetypal Analysis for population genetics

PLoS Comput Biol. 2022 Aug 25;18(8):e1010301. doi: 10.1371/journal.pcbi.1010301. eCollection 2022 Aug.

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 such a 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genetic Predisposition to Disease
  • Genetics, Population
  • Genome
  • Genome-Wide Association Study*
  • Genomics / methods
  • Humans
  • Polymorphism, Single Nucleotide* / genetics

Grants and funding

This work was supported in part by the Chan Zuckerberg Biohub (awarded to CDB) and by the Royal Academy of Engineering Leaders Scholarship (awarded to JGM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.