Fast, accurate local ancestry inference with FLARE

Abstract

Local ancestry is the source ancestry at each point in the genome of an admixed individual. Inferred local ancestry is used for admixture mapping and population genetic analyses. We present FLARE (fast local ancestry estimation), a method for local ancestry inference. FLARE achieves high accuracy through the use of an extended Li and Stephens model, and it achieves exceptional computational performance through incorporation of computational techniques developed for genotype imputation. Memory requirements are reduced through on-the-fly compression of reference haplotypes and stored checkpoints. Computation time is reduced through the use of composite reference haplotypes. These techniques allow FLARE to scale to datasets with hundreds of thousands of sequenced individuals and to provide superior accuracy on large-scale data. FLARE is open source and available at https://github.com/browning-lab/flare.

Keywords: admixture; ancestry; local ancestry inference.

Figure 1

Computation time for simulated sequence data with three-way admixture Wallclock computation time in hours is shown on the y axis. Reference panel size for each of the three ancestries is shown on the x axis. Each analysis includes 100 admixed individuals, and results are averaged over four replicate simulations. Error bars (±2 standard errors) are shown as gray lines. Analyses of a simulated chromosome modeled on human chromosome 20 were run with 20 compute threads. MOSAIC could not analyze the data with 1,000 or more individuals per reference panel within the available 384 GB of computer memory. RFMix could not analyze the data with 10,000 individuals per reference panel within 48 h.

Figure 2

Accuracy when increasing reference panel size for simulated sequence data with three-way admixture The y axis shows squared correlation between true and inferred local ancestry dose averaged over ancestries and across four replicate simulations (details in subjects and methods). Error bars (±2 standard errors) are shown as gray lines. Each of the three ancestries is represented by a reference panel of size shown on the x axis, and each analysis includes 100 admixed individuals. MOSAIC could not analyze the data with 1,000 or more individuals per reference panel within the available 384 GB of computer memory. RFMix could not analyze the data with 10,000 individuals per reference panel within the allotted two days.

Figure 3

Accuracy by ancestry for simulated sequence data with four-way admixture The y axis is the squared correlation between the true and inferred ancestry dose for a single ancestry, averaged across four replicate simulations. Error bars (±2 standard errors) are shown as gray lines. The ancestry is shown on the x axis (AFR is simulated West African, EUR is simulated European, CHB is simulated Han Chinese, JPT is simulated Japanese). The simulated sequence data have 100 admixed individuals and 400 individuals in each of the four reference panels. Results are averaged over four replicate simulations. MOSAIC could not analyze these data within the available 384 GB of computer memory

Figure 4

Accuracy for simulated sequence data with two-way admixture The y axis shows squared correlation between true and inferred local ancestry dose averaged over ancestries and across four replicate simulations (details in subjects and methods). Error bars (±2 standard errors) are shown as gray lines. The x axis shows the split time for the two ancestral populations. Each of the three ancestries is represented by a reference panel of size 200, and each analysis includes 100 admixed individuals.