TypeTE: a tool to genotype mobile element insertions from whole genome resequencing data

Area of Science:

• Genomics
• Population Genetics
• Bioinformatics

Background:

• Alu retrotransposons comprise over 10% of the human genome, contributing to structural variants and influencing gene expression.
• Accurate genotyping of mobile elements like Alus is crucial for understanding population structure and genetic variation.
• Previous Alu genotype calls in large datasets have shown inaccuracies, complicating haplotype phasing.

Purpose of the Study:

• To introduce TypeTE, a novel computational pipeline for accurate Alu insertion genotyping from whole-genome sequencing data.
• To address the challenge of erroneous Alu genotypes and improve their utility as population markers.
• To enhance the analysis of mobile element insertions in population genomics studies.

Main Methods:

• TypeTE utilizes whole-genome sequencing data to identify Alu insertion hallmarks (poly-A tail, target site duplication) and orientation.
• The pipeline employs local re-assembly to reconstruct presence and absence alleles of Alu insertions.
• Sequencing reads are re-mapped to these reconstructed alleles to compute genotype likelihoods.

Main Results:

• TypeTE significantly improves Alu genotype accuracy, increasing it from 83% to 92% in the 1000 Genomes Project dataset.
• Validation was performed using a high-quality set of PCR-based genotyping data for over 200 loci.
• The pipeline demonstrates enhanced accuracy compared to previous genotyping methods.

Conclusions:

• TypeTE provides a valuable tool for accurate Alu insertion genotyping from WGS data.
• The pipeline enhances the reliability of mobile element insertion analysis in population genomics.
• TypeTE is adaptable to other retrotransposon families, broadening its applicability.