fill-aa

Quick Start

• Command: fill-aa [OPTIONS] < in.vcf > out.vcf
• Local executable: /home/vimalinx/miniforge3/envs/bio/bin/fill-aa
• Full reference: See references/help.md for complete options and examples.

When To Use This Tool

• Add AA ancestral-allele annotations to a VCF INFO column.
• Fill ancestral bases from 1000 Genomes-style ancestral FASTA files for SNPs, indels, or reference sites.
• Prepare variant datasets for analyses that need ancestral-state-aware annotations.

Common Patterns

# 1) Annotate a sorted VCF with ancestral alleles
fill-aa -a human_ancestor_ < sorted.vcf > aa.vcf

# 2) Restrict filling to selected event types
fill-aa -a human_ancestor_ -t snp,indel < sorted.vcf > aa_subset.vcf

Recommended Workflow

1. Prepare ancestral allele FASTA files: decompress, rename sequence headers to match chromosome names, compress with gzip (not bgzip), and index with samtools faidx.
2. Ensure input VCF is sorted using vcf-sort to avoid severe performance degradation.
3. Run fill-aa -a <ancestral_prefix> [-t <types>] < in.vcf > out.vcf.
4. Verify output VCF contains AA annotations in the INFO column.

Guardrails

• Input VCF must be sorted; unsorted files cause serious performance issues.
• Ancestral allele FASTA must be gzip-compressed and indexed with samtools faidx.
• Sequence headers in ancestral files must use simple chromosome names (e.g., 1 or chr1).
• --help works, but --version is not implemented and errors as an unknown parameter.
• If the exact -a path does not exist, the script falls back to <prefix><chrom>.fa.gz, so record your naming convention carefully.