Related Experiment Video
Updated: Aug 5, 2026
10:36
Rare Event Detection Using Error-corrected DNA and RNA Sequencing
Published on: August 3, 2018
Highly Accurate Sequencing Methods for Low-Frequency Variant Detection
Farzaneh Darbeheshti1, Azeet Narayan2, Hayet Radia Zeggar1
1Department of Radiation Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, United States.
Clinical Chemistry
|July 29, 2026
Summary
Next-generation sequencing (NGS) accuracy is improved by new methods for low-frequency variant detection. These strategies reduce technical errors, enhancing signal-to-noise ratios for reliable mutation calling.
Area of Science:
- Genomics
- Molecular Biology
- Bioinformatics
Background:
- Next-generation sequencing (NGS) is vital in life sciences but limited by error rates and cost for low-frequency variant detection.
- Sequencing errors stem from DNA damage, library preparation, PCR amplification, and base calling.
- Current accurate methods include single-strand-consensus and duplex-consensus approaches.
Purpose of the Study:
- To review error correction strategies in NGS.
- To highlight innovations improving sequencing accuracy and efficiency.
- To address limitations in low-frequency variant detection.
Main Methods:
- Summarizing principles of single-strand-consensus and duplex-consensus methods.
- Reviewing library preparation and sequencing strategy innovations.
- Discussing computational pipelines for mutation calling.
Main Results:
- New technologies enhance accuracy and efficiency in NGS.
- Error reduction strategies improve low-frequency variant detection.
- Methodological innovations address errors throughout the workflow.
Conclusions:
- Highly accurate sequencing approaches significantly improve low-frequency variant detection.
- These methods reduce technical artifacts and enhance signal-to-noise ratios.
- Advancements in NGS error correction enable more reliable mutation analysis.
Related Concept Videos
03:21RNA-seq
RNA sequencing, or RNA-Seq, is a high-throughput sequencing technology used to study the transcriptome of a cell. Transcriptomics helps to interpret the functional elements of a genome and identify the molecular constituents of an organism. Additionally, it also helps in understanding the development of an organism and the occurrence of diseases.
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while microarray-based...
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while microarray-based...
01:57Sanger Sequencing
DNA sequencing is a fundamental technique that is routinely used in the biological sciences. This method can be applied to a range of questions at different scales - from the sequencing of a cloned DNA fragment or the study of a mutation in a gene up to whole-genome sequencing. However, despite the widespread use of sequencing today, it was not until 1977 that Fredrick Sanger and his collaborators developed the chain-termination method to decode DNA sequences. It relies on the separation of a...
03:00Next-generation Sequencing
The first human genome sequencing project cost $2.7 billion and was declared complete in 2003, after 15 years of international cooperation and collaboration between several research teams and funding agencies. Today, with the advent of next-generation sequencing technologies, the cost and time of sequencing a human genome have dropped over 100 fold.
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features.
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features.
01:29Modern Molecular Taxonomy
Advancements in molecular biology have revolutionized the identification and characterization of bacteria, with multiple methods leveraging DNA sequencing for enhanced precision. As sequencing technologies improve and costs decline, these approaches are increasingly used in clinical, environmental, and evolutionary studies.Multilocus Sequence Typing (MLST) examines several housekeeping genes, essential chromosomal genes encoding cellular functions, to distinguish strains. Approximately...