reference-genome-local-ancestry

Author

Saideep Gona

Published

March 27, 2023

Code

suppressMessages(library(tidyverse))
suppressMessages(library(glue))
PRE = "/Users/sgona/Library/CloudStorage/Box-Box/imlab-data/data-Github/Daily-Blog-Sai"

## COPY THE DATE AND SLUG fields FROM THE HEADER
SLUG="reference-genome-local-ancestry" ## copy the slug from the header
bDATE='2023-03-27' ## copy the date from the blog's header here
DATA = glue("{PRE}/{bDATE}-{SLUG}")
if(!file.exists(DATA)) system(glue::glue("mkdir {DATA}"))
WORK=DATA

Context

One thing we hadn’t yet taken a look at is the local ancestry of genes in the reference genome. This is a useful metric which should be included in our gene metadata.

Other to-dos: Normalize before modeling epistasis Model demographic covariates in epistasis

Assigning local ancestry to genes

Fortunately I was able to acquire some precomputed local ancestry inference from the following link provided by the McCoy lab: https://ftp-trace.ncbi.nlm.nih.gov/ReferenceSamples/giab/release/genome-stratifications/v3.1/GRCh38/ancestry/

The following steps are for creating assignments of local ancestry to genes based off the files above. First lets concatenate all the bed files and sort them:

Add an ancestry column to each bed file:

Code

library(tidyverse)

ancestries <- c("AFR","AMR","EAS","EUR","SAS")
root_dir <- "/Users/sgona/Library/CloudStorage/Box-Box/imlab-data/data-Github/analysis-Sai/metadata/ref_local_ancestry"
for (ancestry in ancestries) {
  current_bed <- paste0(root_dir,"/GRCh38_ancestry_",ancestry,".bed")
  tagged_bed <- paste0(root_dir,"/GRCh38_ancestry_",ancestry,"_tagged.bed")
  
  current_bed_table <- read.delim(current_bed,skip = 1, header = FALSE)
  current_bed_table$ancestry <- ancestry
  current_bed_table <- current_bed_table %>% transform(V1=str_replace(V1,"chr",""))
  
  write.table(current_bed_table, tagged_bed, sep="\t", col.names = FALSE, quote = FALSE, row.names = FALSE)
}

Code

import os
import pandas as pd

os.system("cat /Users/sgona/Library/CloudStorage/Box-Box/imlab-data/data-Github/analysis-Sai/metadata/ref_local_ancestry/GRC*_tagged.bed > /Users/sgona/Library/CloudStorage/Box-Box/imlab-data/data-Github/analysis-Sai/metadata/ref_local_ancestry/all_tracks_local_ancestry.bed")

Code

os.system("sort -k 1,1 -k2,2n /Users/sgona/Library/CloudStorage/Box-Box/imlab-data/data-Github/analysis-Sai/metadata/ref_local_ancestry/all_tracks_local_ancestry.bed -o /Users/sgona/Library/CloudStorage/Box-Box/imlab-data/data-Github/analysis-Sai/metadata/ref_local_ancestry/all_tracks_local_ancestry.bed")

Code


import pandas as pd

ancestry_db = []
with open("/Users/sgona/Library/CloudStorage/Box-Box/imlab-data/data-Github/analysis-Sai/metadata/ref_local_ancestry/all_tracks_local_ancestry.bed", "r") as all:
  for line in all:
    p_line = line.strip().split("\t")
    ancestry_db.append(p_line)

print(len(ancestry_db))

Code

ancestry_ind = 0    
gene_region_ancestry = {}
with open("/Users/sgona/Library/CloudStorage/Box-Box/imlab-data/data-Github/analysis-Sai/metadata/protein_coding_nosex.bed", "r") as genes:
    for line in genes:
        p_line = line.strip().split("\t")
        cur_chrom = p_line[0].lstrip("chr")
        cur_start = int(p_line[1])
        cur_end = int(p_line[2])
        cur_gene = p_line[3].split(".")[0]
        # print(cur_gene)
        # print(cur_chrom)
        # print(cur_start,cur_end)
        
        local_count = {"AFR":0,
                        "AMR":0,
                        "EAS":0,
                        "SAS":0,
                        "EUR":0,
                        "NA":0}
                        
        total_anc_count = 0
        
        gene_complete=False
        
        local_counter = 0
        while not gene_complete:
            local_counter += 1
            if local_counter % 10000 == 0:
                # print(cur_chrom,cur_start,cur_end)
                # print(a_chrom,a_start,a_end)        
                print(ancestry_ind)
                print("1000")
                a_start = int(ancestry_db[ancestry_ind][1])
                a_end = int(ancestry_db[ancestry_ind][2])
                a_ancestry = ancestry_db[ancestry_ind][3]
                # print(a_chrom,a_start,a_end)

            if ancestry_ind >= (len(ancestry_db) - 1):
                print("ancestry_ind exceeds db", ancestry_ind,len(ancestry_db))
                break
            # print(local_count)
        #   print(ancestry_db[ancestry_ind])
            a_chrom = ancestry_db[ancestry_ind][0]
            if a_chrom in ["X","Y"]:
                ancestry_ind += 1
                continue
            if a_chrom != cur_chrom:
                print("chrom",cur_chrom,a_chrom)
                if int(a_chrom) < int(cur_chrom):
                    ancestry_ind += 1
                    continue
                gene_complete = True
                continue
        
            a_start = int(ancestry_db[ancestry_ind][1])
            a_end = int(ancestry_db[ancestry_ind][2])
            a_ancestry = ancestry_db[ancestry_ind][3]

            # print("cur",cur_chrom,cur_start,cur_end)
            # print("a",a_chrom,a_start,a_end)

            # Outside gene
            if a_end <= cur_start:
                ancestry_ind += 1
                continue
            if a_start >= cur_end:
                gene_complete = True
                local_count["NA"] = cur_end-cur_start-total_anc_count
                continue
            # Left partial overlap
            if a_start < cur_start:
                if cur_start < a_end < cur_end:
                    local_count[a_ancestry] += (a_end-cur_start)
                    total_anc_count += (a_end-cur_start)
                    ancestry_ind += 1
                    continue     
            # Complete overlap
            if a_start >= cur_start:
                if a_end <= cur_end:
                    local_count[a_ancestry] += (a_end-a_start)
                    total_anc_count += (a_end-a_start)
                    ancestry_ind += 1
                    continue 
            # Right partial overlap
            if a_end > cur_end:
                if cur_start < a_start < cur_end:
                    local_count[a_ancestry] += (cur_end-a_start)
                    total_anc_count += (cur_end-a_start)
                    ancestry_ind += 1
                    continue      
            # Larger than gene
            if a_start < cur_start:
                if a_end > cur_end:
                    local_count[a_ancestry] += (cur_end-cur_start)
                    total_anc_count += (cur_end-cur_start)
                    ancestry_ind += 1
                    continue     
        
        gene_region_ancestry[cur_gene] = local_count 
        if ancestry_ind >= (len(ancestry_db) - 1):
            break

# print(gene_region_ancestry)

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419155
1000
429155
1000
ancestry_ind exceeds db 435053 435054

Code

gene_df = pd.DataFrame(gene_region_ancestry)
gene_df.transpose().to_csv("/Users/sgona/Library/CloudStorage/Box-Box/imlab-data/data-Github/analysis-Sai/metadata/ref_local_ancestry/gene_annotations.csv")