Multi-platform framework for mapping somatic retrotransposition in human tissues.

Area of Science:

• Genomics
• Molecular Biology
• Human Genetics

Background:

• Mobile element insertions (MEIs) significantly influence the human genome across germline and somatic tissues.
• Detecting somatic MEIs (sMEIs) in non-cancerous tissues is difficult due to low allelic fractions and repetitive genomic regions.

Purpose of the Study:

• To establish an advanced analytical framework for accurate sMEI detection and characterization.
• To enhance the understanding of sMEI dynamics and their impact on genome structure and evolution.

Main Methods:

• Utilized a combination of long-read sequencing, MEI-targeted sequencing, and advanced bioinformatics.
• Implemented haplotype phasing and donor-specific assemblies for improved sMEI resolution.
• Developed a novel source-tracing strategy based on internal sequence variation.

Main Results:

• Benchmarked sMEI detection methods, highlighting the efficacy of long-read and targeted sequencing for low-frequency events.
• Successfully distinguished sMEIs from germline insertions and artifacts in silico.
• Identified 18 rare somatic L1 insertions in donor tissues, revealing significant structural and source diversity.

Conclusions:

• The developed framework provides a robust approach for mapping sMEIs in diverse human tissues.
• This study expands the known repertoire of active mobile elements and offers crucial biological insights into somatic genome variation.