Last updated: 2020-05-21

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Knit directory: drift-workflow/analysis/

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Here I visualize population structure with simulated data from the AmericanAdmixture_4B11 scenario. See Browning et al. 2018 for details.

Below, I show a number of EBMF solutions and in each of them I don’t display the first shared factor which is prefixed to the one-vector and scale the loadings by the prior variance. I only describe the loadings that remain after the shared factor.

Imports

Import the required libraries and scripts:

suppressMessages({
  library(lfa)
  library(flashier)
  library(drift.alpha)
  library(ggplot2)
  library(RColorBrewer)
  library(reshape2)
  library(tidyverse)
  library(alstructure)
  source("../code/structure_plot.R")
})

Data

data_path <- "../output/simulations/AmericanAdmixture_4B11/rep2.txt"
G <- t(as.matrix(read.table(data_path, sep=" ")))
colnames(G) <- NULL
rownames(G) <- NULL
n <- nrow(G)
daf <- colSums(G) / (2 * n)
colors <- brewer.pal(8, "Set2")

# filter out too rare and too common SNPs
Y <- G[,((daf>=.05) & (daf <=.95))]
p <- ncol(Y)
print(n)
[1] 160
print(p)
[1] 25026
# sub-population labels from stdpop
labs <- rep(c("AFR", "EUR", "ASIA", "ADMIX"), each=40)

we end up with 160 individuals and ~25000 SNPs. View fitted the sample covariance matrix:

plot_cov((1.0 / p) * Y %*% t(Y), as.is=T)

Version Author Date
87a17c5 Joseph Marcus 2020-05-21

flash [greedy]

Run the greedy algorithm:

ones <- matrix(1, nrow = n, ncol = 1)
ls.soln <- t(solve(crossprod(ones), crossprod(ones, Y)))
fl <- flash.init(Y) %>%
  flash.init.factors(EF = list(ones, ls.soln), 
                     prior.family=c(prior.bimodal(), prior.normal())) %>%
  flash.fix.loadings(kset = 1, mode = 1L) %>%
  flash.backfit() %>%
  flash.add.greedy(Kmax=8, prior.family=c(prior.bimodal(), prior.normal()))
Backfitting 1 factors (tolerance: 5.97e-02)...
  Difference between iterations is within 1.0e-01...
Wrapping up...
Done.
Adding factor 2 to flash object...
Adding factor 3 to flash object...
Adding factor 4 to flash object...
Adding factor 5 to flash object...
Factor doesn't significantly increase objective and won't be added.
Wrapping up...
Done.
sd <- unlist(lapply(fl$fitted.g[[2]], '[[', 3))
L <- fl$flash.fit$EF[[1]]
LDsqrt <- L %*% diag(sd)
K <- ncol(LDsqrt)
plot_loadings(LDsqrt[,2:K], labs) + scale_color_brewer(palette="Set2")

Version Author Date
87a17c5 Joseph Marcus 2020-05-21

view structure plot:

create_structure_plot(L=LDsqrt[,2:K], labels=labs, colors=colors)

Version Author Date
87a17c5 Joseph Marcus 2020-05-21

view fitted covariance matrix:

plot_cov(LDsqrt %*% t(LDsqrt), as.is=T)

Version Author Date
87a17c5 Joseph Marcus 2020-05-21

the greedy algorithm picks up a bit of a signal of admixture but misses out on the African contribution.

flash [backfit]

Run flash [backfit] initializing from the greedy solution:

flbf <- fl %>% 
  flash.backfit() %>% 
  flash.nullcheck(remove=TRUE)
Backfitting 4 factors (tolerance: 5.97e-02)...
  Difference between iterations is within 1.0e+03...
  Difference between iterations is within 1.0e+02...
  Difference between iterations is within 1.0e+01...
  Difference between iterations is within 1.0e+00...
  Difference between iterations is within 1.0e-01...
  Difference between iterations is within 1.0e-02...
Wrapping up...
Done.
Nullchecking 4 factors...
Done.
sd <- unlist(lapply(flbf$fitted.g[[2]], '[[', 3))
L <- flbf$flash.fit$EF[[1]]
LDsqrt <- L %*% diag(sd)
K <- ncol(LDsqrt)
plot_loadings(LDsqrt[,2:K], labs) + scale_color_brewer(palette="Set2")

Version Author Date
87a17c5 Joseph Marcus 2020-05-21

view structure plot:

create_structure_plot(L=LDsqrt[,2:K], labels=labs, colors=colors)

Version Author Date
87a17c5 Joseph Marcus 2020-05-21

view fitted covariance matrix:

plot_cov(LDsqrt %*% t(LDsqrt), as.is=T)

Version Author Date
87a17c5 Joseph Marcus 2020-05-21

The backfitting algorithm misses out on the signal of admixture and finds only 3 population specific factors after the shared factor.

drift

Run drift initializing from the greedy solution:

init <- init_from_data(Y, Kmax=6)
dr <- drift(init, miniter=2, 
            maxiter=1000, 
            tol=0.01, 
            verbose=FALSE)

sd <- sqrt(dr$prior_s2)
L <- dr$EL
LDsqrt <- L %*% diag(sd)
K <- ncol(LDsqrt)
plot_loadings(LDsqrt[,2:K], labs) + scale_color_brewer(palette="Set2")

Version Author Date
87a17c5 Joseph Marcus 2020-05-21

view structure plot:

create_structure_plot(L=LDsqrt[,2:K], labels=labs, colors=colors)

Version Author Date
87a17c5 Joseph Marcus 2020-05-21

view fitted covariance matrix:

plot_cov(LDsqrt %*% t(LDsqrt), as.is=T)

Version Author Date
87a17c5 Joseph Marcus 2020-05-21

drift much better represents the admixture signal but misses the EUR/ASIA two population factor.


sessionInfo()
R version 3.5.1 (2018-07-02)
Platform: x86_64-pc-linux-gnu (64-bit)
Running under: Scientific Linux 7.4 (Nitrogen)

Matrix products: default
BLAS/LAPACK: /software/openblas-0.2.19-el7-x86_64/lib/libopenblas_haswellp-r0.2.19.so

locale:
 [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
 [3] LC_TIME=en_US.UTF-8        LC_COLLATE=en_US.UTF-8    
 [5] LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
 [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                 
 [9] LC_ADDRESS=C               LC_TELEPHONE=C            
[11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       

attached base packages:
[1] stats     graphics  grDevices utils     datasets  methods   base     

other attached packages:
 [1] alstructure_0.1.0  forcats_0.5.0      stringr_1.4.0     
 [4] dplyr_0.8.5        purrr_0.3.4        readr_1.3.1       
 [7] tidyr_1.0.2        tibble_3.0.1       tidyverse_1.3.0   
[10] reshape2_1.4.3     RColorBrewer_1.1-2 ggplot2_3.3.0     
[13] drift.alpha_0.0.9  flashier_0.2.4     lfa_1.9.0         

loaded via a namespace (and not attached):
 [1] httr_1.4.1       jsonlite_1.6     modelr_0.1.6     assertthat_0.2.1
 [5] mixsqp_0.3-43    cellranger_1.1.0 yaml_2.2.0       ebnm_0.1-24     
 [9] pillar_1.4.3     backports_1.1.6  lattice_0.20-38  glue_1.4.0      
[13] digest_0.6.25    promises_1.0.1   rvest_0.3.5      colorspace_1.4-1
[17] htmltools_0.3.6  httpuv_1.4.5     Matrix_1.2-15    plyr_1.8.4      
[21] pkgconfig_2.0.3  invgamma_1.1     broom_0.5.6      haven_2.2.0     
[25] corpcor_1.6.9    scales_1.1.0     whisker_0.3-2    later_0.7.5     
[29] git2r_0.26.1     farver_2.0.3     generics_0.0.2   ellipsis_0.3.0  
[33] withr_2.2.0      ashr_2.2-50      cli_2.0.2        magrittr_1.5    
[37] crayon_1.3.4     readxl_1.3.1     evaluate_0.14    fansi_0.4.1     
[41] fs_1.3.1         nlme_3.1-137     xml2_1.3.2       truncnorm_1.0-8 
[45] tools_3.5.1      hms_0.5.3        lifecycle_0.2.0  munsell_0.5.0   
[49] reprex_0.3.0     irlba_2.3.3      compiler_3.5.1   rlang_0.4.5     
[53] grid_3.5.1       rstudioapi_0.11  labeling_0.3     rmarkdown_1.10  
[57] gtable_0.3.0     DBI_1.0.0        R6_2.4.1         lubridate_1.7.4 
[61] knitr_1.20       workflowr_1.6.1  rprojroot_1.3-2  stringi_1.4.6   
[65] parallel_3.5.1   SQUAREM_2020.2   Rcpp_1.0.4.6     vctrs_0.2.4     
[69] dbplyr_1.4.3     tidyselect_1.0.0