Jitterbug: somatic and germline transposon insertion detection at single-nucleotide resolution

Area of Science:

• Genomics
• Molecular Biology
• Bioinformatics

Background:

• Transposable elements (TEs) are key drivers of genome evolution and contribute to phenotypic variation.
• TE insertion polymorphisms are associated with various diseases, including human cancers.
• Accurate characterization of TEs is crucial for understanding genome evolution and genetic diseases.

Purpose of the Study:

• To introduce Jitterbug, a novel computational tool for identifying transposable element insertion sites.
• To enable high-resolution, accurate detection of TE insertions within existing next-generation sequencing (NGS) analysis pipelines.

Main Methods:

• Jitterbug utilizes paired-end mapping and clipped-read signatures from NGS alignments.
• The tool operates on standard BAM files, compatible with common alignment tools (e.g., bwa, bowtie2).
• No realignment to consensus transposon sequences is required.

Main Results:

• Jitterbug achieves single-nucleotide resolution for TE insertion site identification.
• Demonstrated high sensitivity and specificity in human and Arabidopsis genomes.
• Accurate estimation of TE insertion zygosity and identification of somatic insertions.

Conclusions:

• Jitterbug successfully identifies mosaic somatic TE movement in tumor-normal sample pairs.
• The tool facilitates the estimation of cancer cell fraction in clones with somatic TE insertions.
• The evaluation methods contribute to establishing a gold standard for benchmarking structural variant prediction tools.