Related Experiment Video
Updated: Oct 25, 2025
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Aperture: alignment-free detection of structural variations and viral integrations in circulating tumor DNA
Hongchao Liu1, Huihui Yin2, Guangyu Li1
1State Key Laboratory of Medical Molecular Biology, Center for Bioinformatics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences,School of Basic Medicine Peking Union Medical College.
Abstract:
The identification of structural variations (SVs) and viral integrations in circulating tumor DNA (ctDNA) is a key step in precision oncology that may assist clinicians in treatment selection and monitoring. However, due to the short fragment size of ctDNA, it is challenging to accurately detect low-frequency SVs or SVs involving complex junctions in ctDNA sequencing data. Here, we describe Aperture, a new fast SV caller that applies a unique strategy of $k$-mer-based searching, binary label-based breakpoint detection and candidate clustering to detect SVs and viral integrations with high sensitivity, especially when junctions span repetitive regions. Aperture also employs a barcode-based filter to ensure specificity. Compared with existing methods, Aperture exhibits superior sensitivity and specificity in simulated, reference and real data tests, especially at low dilutions. Additionally, Aperture is able to predict sites of viral integration and identify complex SVs involving novel insertions and repetitive sequences in real patient data. Aperture is freely available at https://github.com/liuhc8/Aperture.
Insights
A new tool called Aperture accurately detects structural variations and viral integrations in circulating tumor DNA. This advancement improves precision oncology by enhancing sensitivity and specificity in analyzing low-frequency mutations.
Area of Science:
- Genomics and Bioinformatics
- Cancer Research
- Molecular Diagnostics
Background:
- Precision oncology relies on identifying structural variations (SVs) and viral integrations in circulating tumor DNA (ctDNA) for treatment decisions.
- Detecting low-frequency SVs and complex junctions in short ctDNA fragments presents significant analytical challenges.
Purpose of the Study:
- To introduce Aperture, a novel computational tool designed for sensitive and specific detection of SVs and viral integrations in ctDNA.
- To address the limitations of existing methods in identifying complex SVs and low-abundance variants within ctDNA sequencing data.
Main Methods:
- Aperture utilizes a k-mer-based search strategy combined with binary label-based breakpoint detection and candidate clustering.
- The tool incorporates a barcode-based filter to enhance specificity and accurately identify viral integration sites.
- Performance was evaluated using simulated, reference, and real patient ctDNA sequencing data, including low-dilution samples.
Main Results:
- Aperture demonstrated superior sensitivity and specificity compared to existing SV callers, particularly for low-frequency variants and complex junctions in repetitive regions.
- The tool successfully identified complex SVs, including novel insertions and repetitive sequences, in real patient data.
- Aperture accurately predicted viral integration sites, offering valuable insights for oncological treatment and monitoring.
Conclusions:
- Aperture provides a robust and efficient solution for detecting structural variations and viral integrations in ctDNA.
- The tool's high sensitivity and specificity, especially in challenging scenarios like repetitive regions and low variant frequencies, advance the field of precision oncology.
- Aperture is freely available, facilitating its adoption and further development in clinical and research settings.
