UTR project

Scripts used for Lek Labs UTR project.

General workflow

This analysis relies on canonical intervals, as defined in Ensembl ensembl.org ; gnomAD genomes dataset https://gnomad.broadinstitute.org/; gencode annotation v19 https://www.gencodegenes.org/, uORFs are extracted from from Gerstein lab paper https://doi.org/10.1093/nar/gky188. See comments in scripts for details

1. Import gtf file, and separate UTR3s and UTR5s, then make GATK-compatible intervals files for each region of interest (UTR5, CDS, UTR3) Regions.R
2. Download gnomad vcf file for genomes dataset, and select variants based on the regions defined in #1. region_select.sh
3. Make position dataframe: each position is marked with region and relative position in that region (UTR5 - position from ATG, negative integers; CDS - position from ATG, positive integers; UTR3 position from stop codon, positive integers). Position_dfs.R
4. For ClinVar variants analysis run (Figure 1) ClinVar_variants.R, dependent on #2
5. For uORF analysis run uORFs.R, dependent on #3.
6. For Kozak sequence logio plot run Kozak.R, dependent on #3
7. For ExAC coverage run ExAC_coverage.R.
8. For analysis on allele frequencies and counts of variants in different regions run Figure2.R, dependent on #2 and #3.