Python for local ancestry estimation

• Python 3.5+ is required
• bcftools
• (optionally) plink / plink2

Installing python requirements:

pip3 install -r requirements.txt

Approximate runtime on a modern PC \ server is 1 minute for 9 ancestral populations, 120,000 SNPs and a window size of 50. The memory usage (resident) is about 100-110 megabytes (1 process for 1 sample at a time).

(will be performed by script itself in future)

1. In case we have .bed .bim .fam files, we need to convert to vcf using plink:

plink2 --bfile <bfile_prefix> --recode vcf --out <vcf_file>

2. Calculate snp frequencies for population groups using bcftools. User groups defined in file configs/vcf_groups.txt:

cat <vcf_file> | bcftools view -c 1 -Ou | bcftools +fill-tags -Ou -- -S configs/vcf_groups.txt -t AF | bcftools query -H -f "%CHROM %POS %ID %AF_<group> %AF_Mediterranean %AF_NativeAmerican %AF_NorthEastAsian %AF_NorthernEuropean %AF_Oceanian %AF_SouthAfrican %AF_SouthEastAsian %AF_SouthWestAsian %AF_SubsaharanAfrican\n" > <group>.<sample>.txt

In case vcf file is (b)gzipped use samtools tabix.

Currently supported modes:

python3 src/bayesian_pipeline.py --sample <sample_name> --admixtures <admixture_vectors_file> --window-len 50 <group>.<sample>.txt

python3 src/bayes_viterbi.py --sample <sample_name> --admixtures <admixture_vectors_file> --window-len 50 <group>.<sample>.txt -m --viterbi-alpha 1

-m option is used to switch "merged" window mode (windows will overlap by 1 SNP) --viterbi-alpha is a regularization parameter, according to our tests with 1kG and generated data we recommend 10000 as a starting value for experiments.

plink2 --bfile sample.txt_GENO --recode vcf --out sample

cat sample.vcf | bcftools view -c 1 -Ou | bcftools +fill-tags -Ou -- -S vcf_groups.txt -t AF | bcftools query -H -f "%CHROM %POS %ID %AF_QuechuaCandelaria_3 %AF_Mediterranean %AF_NativeAmerican %AF_NorthEastAsian %AF_NorthernEuropean %AF_Oceanian %AF_SouthAfrican %AF_SouthEastAsian %AF_SouthWestAsian %AF_SubsaharanAfrican\n" > "population.sample.txt"

python3 src/bayesian_pipeline.py --window-len 50  "population.sample.txt"

Also, you can find and run the example pipeline from the archive example_pipeline.tar.gz

As a result of the pipeline we get 3 files:

1. <group>_<mode>_<window-len>_predictions.csv
   Csv file with a list of most probable population in each window.

2. <group>_<mode>_<window-len>_snp_prob.tsv
   Tsv (tab-separated) file with a list of all SNPs and probabilities that it came from each population.

3. <group>_<mode>_<window-len>_stats.csv
   Csv file with statistics that shows the fraction of windows assigned to each population.

Depending on your needs you might need only one file or all of them.

Using PyLAE with different genomes and/or sets of markers A different set of putative ancestral populations or a different set of markers require additional processing. First, we need to collect a database of putatively un-admixed individuals. If there is an existing validated set of ancestry informative features, these markers should run the admixture in supervised mode. For each self-reported ancestry, samples should be clustered based on their admixture profiles to identify subgroups within each self-reported ancestry. These subgroups are then examined using information about the studied population's history, and the most representative subset is retained. Then, putative ancestral populations (from 15 to 20 individuals per group) are generated for every ancestry. The validity and stability of the ancestral populations are evaluated using 1) PCA, 2) leave-one-out supervised admixture, and 3) by application of supervised admixture to the original datase

Algorithm can be split into 4 stages:

• Data preparation
• Calculating probabilities of assigning each SNP to populations using naive bayes algorithm.
• Choosing best population for each window with selected length (in SNPs).
  In this slog (p). Then this information (I) is summed in each window and the window is assigned to population with max I. Pop = argmax(I)
• Calculating fraction of windows assigned to each population.

https://www.biorxiv.org/content/10.1101/2020.11.13.380105v1