EnsembleTR is a tool for ensemble Tandem Repeat (TR) calling. It takes one or more VCF files with TR genotypes for a panel of samples and outputs a consensus set of genotypes.
pip install --upgrade pip
pip install ensembletr
Type ensembletr --help. You should see the help message appear.
To run EnsembleTR, use the following command
ensembletr --out output.vcf
--ref ref.fa
--vcfs vcf1.vcf,vcf2.vcf,...
Required parameters:
--vcfs <file.vcf,[file2.vcf]>Comma separated list of input VCF files--refRefererence genome (.fa)--outPath to output VCF file
Both zipped and unzipped VCF files are accepted as input. EnsembleTR can currently process VCF files generated by hipSTR, GangSTR, adVNTR, and ExpansionHunter.
You must input a reference genome in FASTA format. This must be the same reference build used for TR calling in input files.
For more information on VCF file format, see the VCF spec. The output VCF is not necessarily sorted, please use vcf-sort or other VCF sorting tools to sort the output before downstream analysis. EnsembleTR output VCF file contains several fields described below.
INFO fields contain aggregated statistics about each TR. The following custom fields are added:
| FIELD | DESCRIPTION |
|---|---|
| START | Start position of the TR |
| END | End position of the TR |
| PERIOD | Length of the repeat unit |
| RU | Repeat motif |
| METHODS | Methods that attempted to genotype this locus (AdVNTR, EH, HipSTR, GangSTR) |
Note that the RU shows the canonical sequence of the repeat unit, which is the first alphabetically out of all possible rotations on + and - strands of the sequence. e.g. "TG" canonical sequence is "AC".
FORMAT fields contain information specific to each genotype call. The following custom fields are added:
| FIELD | DESCRIPTION |
|---|---|
| GT | Genotype |
| GB | Base pair difference from ref allele |
| NCOPY | Genotype given in number of copies of the repeat motif |
| EXP | Boolean showing if the genotype alleles were expanded |
| SCORE | Score of the consensus call |
| GTS | Method(s) that support the consensus call |
| ALS | Number of times each bp difference was seen across all calls |
| INPUTS | Raw calls |
Score is calculated by aggregating quality information from calls that are getting merged at each locus.
You can use statSTR from TRTools to compute various per-locus statistics for EnsembleTR .VCF files.
For example, to compute per-locus allele frequency use the following command:
statSTR --vcf EnsembleTR_file.vcf.gz
--vcftype hipstr
--afreq
--out EnsembleTR_per_locus_allele_frequency
Chromosome 1 VCF file and tbi file
Chromosome 2 VCF file and tbi file
Chromosome 3 VCF file and tbi file
Chromosome 4 VCF file and tbi file
Chromosome 5 VCF file and tbi file
Chromosome 6 VCF file and tbi file
Chromosome 7 VCF file and tbi file
Chromosome 8 VCF file and tbi file
Chromosome 9 VCF file and tbi file
Chromosome 10 VCF file and tbi file
Chromosome 11 VCF file and tbi file
Chromosome 12 VCF file and tbi file
Chromosome 13 VCF file and tbi file
Chromosome 14 VCF file and tbi file
Chromosome 15 VCF file and tbi file
Chromosome 16 VCF file and tbi file
Chromosome 17 VCF file and tbi file
Chromosome 18 VCF file and tbi file
Chromosome 19 VCF file and tbi file
Chromosome 20 VCF file and tbi file
Chromosome 21 VCF file and tbi file
Chromosome 22 VCF file and tbi file
Phased variants of 3,202 samples from the 1000 Genomes Project (1kGP).
TRs imputed from 3,202 1kGP samples.
Total 70,692,015 variants + 1,091,550 TR markers.
All the coordinates are based on hg38 human reference genome.
Chromosome 1 VCF file and tbi file
Chromosome 2 VCF file and tbi file
Chromosome 3 VCF file and tbi file
Chromosome 4 VCF file and tbi file
Chromosome 5 VCF file and tbi file
Chromosome 6 VCF file and tbi file
Chromosome 7 VCF file and tbi file
Chromosome 8 VCF file and tbi file
Chromosome 9 VCF file and tbi file
Chromosome 10 VCF file and tbi file
Chromosome 11 VCF file and tbi file
Chromosome 12 VCF file and tbi file
Chromosome 13 VCF file and tbi file
Chromosome 14 VCF file and tbi file
Chromosome 15 VCF file and tbi file
Chromosome 16 VCF file and tbi file
Chromosome 17 VCF file and tbi file
Chromosome 18 VCF file and tbi file
Chromosome 19 VCF file and tbi file
Chromosome 20 VCF file and tbi file
Chromosome 21 VCF file and tbi file
Chromosome 22 VCF file and tbi file
Use Beagle to impute TRs into SNP data:
java -Xmx4g -jar beagle.version.jar \
gt=SNPs.vcf.gz \
ref=${chrom}_final_SNP_merged.vcf.gz \
out=imputed_TR_SNPs
Please use the version 5.4 for this analysis as we had issues with the newer versions of Beagle and we are right now communicating it with Beagle developers.
Per locus summary statistics can be downloaded from here. Each table has information on coordinates, repeat unit sequence, and potential overlap with genes listed in GENCODE v22 for repeats in EnsembleTR catalog.
Population-specific per locus statistics on allele frequency, heterozygosity, and the number of called samples can be found here. Statistics are computed using statSTR from the TRTools package.
For version I of EnsembleTR calls, please use https://ensemble-tr.s3.us-east-2.amazonaws.com/split/ensemble_chr"$chr"_filtered.vcf.gz for VCF file and https://ensemble-tr.s3.us-east-2.amazonaws.com/split/ensemble_chr"$chr"_filtered.vcf.gz.tbi for tbi file.
For version I of phased panels, please use https://ensemble-tr.s3.us-east-2.amazonaws.com/phased-split/chr"$chr"_final_SNP_merged.vcf.gz for VCF file and https://ensemble-tr.s3.us-east-2.amazonaws.com/phased-split/chr"$chr"_final_SNP_merged.vcf.gz.csi for tbi file.
HipSTR might expand the coordinates of the repeat if there is a nearby SNP. If you have multiple HipSTR outputs from different individuals and want to use mergeSTR to merge them, please use our python script, Hipstr_correction.py, to correct the merged HipSTR VCF file ensuring that multiple records from the same repeat culminate in a single unified record.
python3 HipSTR_correction_faster.py hipstr_merged_by_mergeSTR.vcf.gz hipstr_merged_corrected.vcf
bgzip hipstr_merged_corrected.vcf
tabix -p vcf hipstr_merged_corrected.vcf.gz